The country’s trajectory has been building for years. A fast-growing middle-income population, rising chronic disease burden, and expanding health infrastructure have created both demand and urgency. What is changing now is the environment in which innovation can move, driving faster approvals, a culture of collaboration, digital infrastructure and a government signaling policy readiness to engage global partners in shaping the next era of medicine.

The economic momentum is significant. The Indian health ecosystem has expanded from roughly $372 billion in 2023 to $638 billion in 2025, making it one of the fastest-growing major health markets in the world. The broader industry is expected to exceed $610 billion by 2026, fueled by rising insurance coverage, expanding hospital infrastructure, and growing demand for chronic disease management. Health growth in India continues at approximately 10–12 percent annually, well above the growth rates typical of mature markets, reflecting both rising access and structural transformation.

BIOAsia 2026 reflects this inflection point. The global gathering in Hyderabad, themed “TechBio Unleashed: AI, Automation & the Biology Revolution,” highlights the (bio)convergence of biology, data, and intelligent systems reshaping health worldwide. Organizers emphasize that the meeting aims to drive health transformation and reinforce India’s position as a leading global life sciences force. For multinational innovators, the message is increasingly clear: India is not only where innovation is deployed; it is also where it is developed. It is where innovation is increasingly defined. India has become a go-to market for multinational enterprises.

Policy Signals and Market Scale: From Opportunity to Strategic Partnership

India’s regulatory and policy environment is evolving in ways that matter deeply to multinational innovators. One pivotal shift came with the country’s decision to allow certain medicines approved in specified developed markets to launch without local clinical trials, a move designed to accelerate patient access while aligning more closely with global regulatory science. This policy shift reflected confidence in international data, a commitment to innovation, and recognition that faster access must remain central to national health strategy.

The scale of India’s pharmaceutical and life sciences market reinforces this transformation. The pharmaceutical sector reached approximately $68 billion in 2025 and is projected to grow to more than $170 billion during the next decade, driven by expanding middle-income demand and strong domestic manufacturing. India already supplies roughly one-fifth of the world’s generic medicines. It produces the majority of global vaccines by volume, positioning the country as a central player in global health supply chains.

As Aman Gupta of SPAG/FINN wrote in Medika Life, “India’s health sector is undergoing a profound transformation, bolstered by government-led reforms and a favorable FDI regime. The allowance of 100% foreign direct investment through automatic routes in health and related sectors has already attracted global giants.” His observation reinforces a central reality for multinational innovators: India’s policy environment is increasingly designed not only to welcome global participation, but to encourage long-term strategic partnership in building the future of healthcare.

Investment trends tell the same story. Health and pharmaceutical private equity and venture investments have reached multi-billion-dollar levels annually. At the same time, India’s contract drug development and manufacturing sector is projected to exceed $22 billion within the next decade. These dynamics position India as a growth market and as a strategic partner across the innovation lifecycle from discovery and clinical development to manufacturing and global distribution.

Shakthi Nagappan, CEO of Telangana Life Sciences Foundation, captured this moment clearly, noting that BIOAsia arrives at a time when technology and biology are redefining healthcare and creating “unprecedented opportunities for innovation, investment, and impact.” The language reflects partnership rather than transaction, a signal that India is moving from market opportunity to strategic collaboration.

Digital Infrastructure, BIOAsia and the Multinational Innovation Imperative

India’s digital transformation may be its most potent catalyst for long-term health innovation. Unlike many mature systems, the country is building a national-scale digital health infrastructure designed to connect patients, providers, and health systems across a population of more than 1.4 billion people, with a rising middle class of 400 million.

The Global Digital Health Market is projected to grow from USD 288.55 billion in 2024 to USD 2,688 billion by 2035, expanding at a CAGR of 22.55% during 2025–2035. This surge is driven by the rapid adoption of AI-powered diagnostics, telemedicine, wearable devices, and data analytics solutions that are revolutionizing patient care and operational efficiency worldwide.

Hundreds of millions of citizens are already using digital health services, including telemedicine, electronic prescriptions, and remote care. The Ayushman Bharat Digital Mission is creating an interoperable national health ecosystem, enabling secure health records, improved care coordination, and population-scale data infrastructure that supports research, real-world evidence, and precision health.

For multinational companies, this digital backbone creates a uniquely strategic environment, enabling large-scale clinical research, faster pharmacovigilance, AI-supported health insights, and rapid deployment of innovation across diverse populations. India’s digital infrastructure is not simply modernizing health delivery. It is enabling national-scale transformation.

BIOAsia sits at the center of this conversation and convergence. The gathering reflects India’s ambition to lead at the intersection of biology, artificial intelligence, and scalable innovation. Leaders from industry, government, and science convene not only to discuss growth but to shape the next phase of global life sciences, where biology, data, and digital systems converge to influence global health.

One conference panel, among the many high-powered sessions, brings together global leaders in advanced therapeutics to explore how next-generation modalities are moving from discovery to scalable care. Panelists across biopharma, translational science, and hospital systems are examining progress in cell and gene therapies, mRNA, and radiopharmaceuticals, underscoring that innovation now depends as much on manufacturable scale and delivery as on scientific breakthrough. India’s expanding capabilities in clinical research and bioprocessing strengthen its role as a key partner in advancing next-generation therapies.

For multinational innovators, the implications are clear. Engagement in India now extends beyond commercialization. It calls for collaboration in research, investment in digital and scientific ecosystems, alignment with national health priorities and partnership in strengthening health delivery.

India’s Strategic Role in Global Health Innovation

India’s rise in global health innovation reflects the alignment of policy, market growth, digital infrastructure, and scientific capability forces that together are reshaping where and how healthcare innovation occurs.

For multinational companies, India now represents a full-spectrum innovation environment. It is a place to conduct clinical research across diverse populations, scale manufacturing and supply chains, deploy digital health at a national scale, and co-develop solutions addressing both local and global health challenges. Increasingly, India is not simply a recipient of innovation developed elsewhere. It is becoming a co-creator of next-generation health.

This shift changes the strategic equation. Market entry alone is no longer sufficient. Meaningful engagement requires partnership with policymakers, regulators, scientists, health providers, and digital health ecosystems. Organizations that invest in collaboration, align with national health priorities, and contribute to strengthening healthcare systems are most likely to succeed in India’s evolving landscape.

BIOAsia sets the stage for this transformation. It is more than a conference. It is a convergence of global health ambition, scientific capability, and policy momentum. The conversations taking place in Hyderabad mirror a broader reality: the geography of health innovation is expanding, and India is now central to its future.

For global health innovators, the question is no longer whether India matters. The question is how deeply they choose to engage in shaping what comes next.

The post India: The Growing Focal Point for Health Innovation appeared first on Medika Life.

Perhaps the biggest wild card is Donald J. Trump’s return to the White House and the nomination of several candidates who have suggested that they will reinvent Health and Human Services, the Food and Drug Administration, Centers for Disease Control, and the Centers for Medicare and Medicaid Services—key agencies that set the agenda for public health and innovation.

The second unknown is the thin line separating misinformation from disinformation.  Historically, we looked to public health scientists to guide us.  Now, we are uncertain who to trust regarding health information.  Advice:  Do not rely on “X” as a fact-checking source – it’s merely noise.  But can you trust significant news sources, C-Suite execs, or elected officials?  It’s hard to say.  There is a vast divide between an honest mistake and willful deception. When it comes to health, do your homework – always!

A third factor must be included in the many 2024 health rankings and “Top 10” analyses that will appear in the days ahead. Our planet’s and people’s health are deeply intertwined. Rising temperatures, air pollution, and extreme weather events are not just environmental concerns but public health emergencies. These factors disproportionately impact vulnerable populations, exacerbating chronic conditions like asthma, cardiovascular disease, and mental health disorders. Addressing these challenges requires health professionals to embrace a broader perspective, recognizing that the fight for cleaner air, sustainable food systems, and resilient communities is inseparable from the mission to improve individual health outcomes.

Here are 10 health-sector developments—not ranked—to watch in the coming year, determined by media coverage, reader interest, and personal interest. These “10” could be Top Hundreds or Thousands. Happily, there were many advancements in 2024 to applaud. Yet, the pain points, too, are many. There are many publication lists to check – reviewing many is worthwhile. What is most important is to reflect on the needs of people and planet and commit to make a difference. The planet doesn’t need people. People need the planet. Equally so, people need each other.

This list’s topics were selected using data from global news outlets, academic publications, press releases, analytics platforms like Google Trends, and social media engagement metrics. While the list reflects the broad measure of public interest, it provides an overview of some of the positive and most worrisome health shifts and signals of what lies ahead.

1. AI-Powered Diagnostics Revolutionize Early Detection

Augmented implementation (AKA artificial intelligence) will redefine diagnostics in the years ahead. AI is poised to redefine diagnostics, with breakthroughs in the early detection of diseases like pancreatic cancer offering unprecedented accuracy and saving lives. Recent breakthroughs set the stage for broader adoption of AI in detecting other cancers and chronic diseases in 2025 and beyond, enticing the biopharma sector to interest in clinical trials to develop treatments for these deadly cancers.  This is a prime example of where AI can become a tipping point for earlier interventions and better patient outcomes globally.

2. India Leadership in Affordable Vaccine Development

India is quietly solidifying a reputation as the “pharmacy of the world” through several initiatives, such as launching a low-cost universal flu vaccine. Developed through a groundbreaking public-private partnership, this vaccine leverages advanced mRNA technology to provide broad-spectrum protection against multiple flu strains. By prioritizing affordability and accessibility, the initiative aims to protect millions of people in low- and middle-income countries, showcasing a scalable model for addressing global health inequities.

India has all the pieces to become a more significant player in the life science innovation puzzle – talent, scientific rigor, and an open-minded government willing to align its drug regulatory system with the world’s gold standard – the Food and Drug Administration.

India’s new rare disease center in New Delhi addresses critical global health gaps, setting a precedent for similar initiatives worldwide. Keep an eye on future developments from India to the world and investments from US-based life science companies in India’s strong talent base.

3. Breakthroughs in Alzheimer’s Disease Treatment

A novel gene-editing therapy targeting the APOE4 gene variant in the United States shows promise in addressing Alzheimer’s progression, and three new drugs were approved in the United Kingdom that may slow down memory decline in early Alzheimer’s disease. This continuing commitment by life science companies to invest in Alzheimer’s treatments after waves of disappointments could mark a turning point in one of the most vexing and worrisome neurodegenerative diseases.

Additionally, long-standing preventive disease pioneer Dean Ornish, MD, Founder and President of the Preventative Medicine Research Institute, has shown a possible pathway to reversing Alzheimer’s symptoms without medication. Ornish’s research on lifestyle interventions—emphasizing diet, exercise, and stress management—gained significant attention in 2024 and highlights the role of holistic approaches in improving cognitive health. His pathway does not dismiss using prescription medicine. Leading medical minds and consumers’ minds should take lifestyle medicine seriously.  It’s not the first time that Dr. Ornish has been proven right.

4. United Kingdom Moves Toward Digital Health Leadership

The United Kingdom launched a nationwide digital health initiative integrating wearable technology with its revered National Health Service (NHS). By enabling people to track chronic conditions like diabetes and hypertension in real-time, the initiative enhances patient engagement and accelerates preventive care delivery. Early results indicate improved patient outcomes and reduced hospital admissions. Looking ahead, 2025 could see the expansion of this initiative to include predictive analytics, further enhancing preventative care and patient empowerment.

UK Finance Minister/Chancellor Rachel Reeves announced in 2024 that the government is increasing the national health budget by US$29.33bn, a significant increase in NHS resourcing. Increased investment in infrastructure, technology and patient care position the United Kingdom as a launching point for new biomedical research and innovation waves.

5. Cancer Vaccines Gain Momentum

Personalized cancer vaccines emerged as a game-changing innovation in oncology. These vaccines train the immune system to target and destroy cancer cells based on the unique genetic mutations in an individual’s tumor, offering a highly tailored approach to treatment. A U.S.-based biotech company reported successful Phase 3 trial results for a melanoma vaccine, demonstrating significant reductions in recurrence rates.  

One promising example is the Moderna and Merck mRNA-based vaccine program for adjuvant treatment of high-risk melanoma. In Phase IIb results, the therapy showed a 44 percent lower risk of cancer recurrence or death compared to Merck blockbuster cancer drug Keytruda alone. Ongoing trials are exploring its efficacy in combating other cancers, such as lung and breast cancer. These are rigorous clinical programs with all the scientific peer-review requirements of a new medication.

6. America Begins to Take Serious Note of Obesity

The United States has finally begun to address obesity as a serious health concern. New policies and initiatives have been implemented to combat this epidemic, including improved access to nutrition education, increased funding for obesity research, and the development of innovative treatment options. Food and Drug Administration approval of new weight-loss GLP-1 drugs has sparked hope for more effective interventions. Additionally, public health campaigns have raised awareness about the long-term health risks associated with obesity, leading to a shift in societal attitudes and increased support for those struggling with weight management.

While weight-loss drugs offer promise, addressing obesity as a multifaceted health issue—spanning diabetes, heart disease, and more—remains critical. However, medications alone are not the miracle solution to the world’s weight problem. Will 2025 become the year of recognizing obesity as an umbrella disease?

7. Israeli Innovation –  Resilience Under Pressure

Sudden attacks from all directions would consume any nation’s emotional and physical energies. If so, the past 16 months should absolutely distract Israel – a country the size of New Jersey – and its nine million Jewish, Muslim, and Druze citizens – from anything other than self-defense.  Despite incredible challenges, Israel continues to innovate, with its 1,600 life science companies driving advancements in digital health, diagnostics, and bio-convergence. Israeli startups raised $2.43 billion in the third quarter of 2024 across 99 rounds, representing a 32 percent increase compared to the same period in 2023 (pre-October 2023)

The number of groundbreaking Israeli-developed medical devices, biologics, and information technologies incorporated into US-headquartered life science companies’ pipelines and product portfolios secures this nation’s position as a global innovator hub. Its role model hospital, Sheba Medical Center, ranks among the world’s top health systems and seamlessly integrates the country’s cutting-edge technologies in intensive care, telemedicine, early diagnostics, smart surgical equipment, and digital imaging throughout its system.

Israel is taking another leap in health innovation through its investment in bio-convergence. It is poised to play a significant role in the next technological wave of the 21st century. 

8. US Advances in Regenerative Medicine

Regenerative medicine focuses on repairing or replacing damaged tissues and organs, tapping into the body’s natural healing processes. Innovations like stem cell regeneration, cell therapy, diabetes and regenerative knee treatments offer alternatives to invasive surgeries and improve outcomes for chronic conditions.

Regulatory frameworks are crucial to this progress, providing clear guidelines and streamlined approval processes to ensure safety while fostering innovation. As regenerative medicine reshapes health delivery, it stands out as a transformative force in addressing some of the most pressing medical challenges. It is science fiction in many ways—maintain an open mind.

9. Global Antimicrobial Resistance Collaboration

The WHO’s global antimicrobial resistance network is a critical step in combating superbugs. It enables real-time data sharing to identify resistance patterns and drive new antibiotic development. It is a big deal. In a world where pathogens know no borders, collective action through such a network is essential to safeguarding the efficacy of treatments and protecting lives worldwide. The urgency has willing partners ready to engage.

This collaborative surveillance network is a big step forward in the response to a silent pandemic threatening global health. Coordinated action across nations equips health systems with real-time tools to identify and respond to resistance patterns. The rise of drug-resistant infections undermines decades of medical progress, turning treatable conditions into life-threatening challenges. A unified surveillance network enhances early detection and targeted interventions and drives the development of new antibiotics and stewardship programs.  Watch what happens in the coming year – our well-being is at stake.

10. A New White House Administration – Anxiety Versus Reality

As the second Trump administration prepares to take up residence in the White House, health ecosystem stakeholders are abuzz about potential policy shifts. Drawing from past actions and election campaign rhetoric, it’s anticipated that this administration – based on executive nominees such as Robert F. Kennedy, Jr., might implement changes through executive authority, bypassing congressional approval.  Food regulation policy is almost a given.  What about access to (some) vaccines? How about the review and regulations of medicines?  Verbal controversy leaves many wondering what will happen next.

The incoming administration’s health policy agenda remains uncertain, with potential changes to the ACA, Medicaid, and reproductive health policies sparking debate. Additionally, there may be moves to restrict access to abortion and contraception, reshape Medicaid through waivers and work requirements, and revise policies affecting LGBTQ+ health and immigration-related health needs.  The possibilities that can generate anxiety are numerous.  Wait and watch!

The Year Ahead and Beyond

These 10 health developments reflect the intersection of innovation, policy, and global collaboration. As we navigate 2025, the focus on improving lives and addressing disparities remains our collective responsibility – to rally to ideas and innovations that can improve people’s and our planet’s well-being.

From AI-supported diagnosis to vaccine breakthroughs in India and digital health leadership in the UK, the global health community demonstrates endless ingenuity. The developments of 2024 offer a roadmap for the future, proving that innovation is a team sport and together can overcome even the most formidable health challenges.

But innovation is like a Jenga structure—pull out the wrong piece at the wrong time, and health innovation can crumble or come to a screeching halt. It rests on three pillars: 1. People, 2. Policy, and 3. Investment. If policies do not support continued biomedical advances, equity and big business will likely search for other sectors that offer promise with a clear vision of a return on investment.

Let’s watch and advocate for a world where health in developed and emerging nations remains a top priority.

The post 2024 Health Trends: Progress, Challenges, and Opportunities appeared first on Medika Life.

Recurrent respiratory papillomatosis (RRP) is just one of those unexpected HPV-driven conditions. RRP is not a sexually transmitted disease and patients are not contagious. An estimated 15,000 to 20,000 people in the United States and more than 125,000 globally have RRP. This burdensome disease takes several forms and impacts people’s upper or lower respiratory tracts or presents as recurrent lesions on the vocal cords or adjacent tissues that require endless corrective surgeries. The treatment often results in permanent damage to a person’s voice.

RRP falls into two demographic subtypes: juvenile-onset (even toddlers) RRP and adult-onset RRP. Each presents unique medical management and lifestyle difficulties, and in addressing these challenges, patient advocacy—raising awareness and building a supportive community—is critically important.

Since it has no Food and Drug Administration (FDA)- approved treatment or cure, patients and scientists devote energy and resources to ensuring people with RRP have access to information. They are in the loop about clinical possibilities for this rare disease. No cure doesn’t mean there is no action!

Beyond the physical challenges of dealing with the disease – and the missed life events and career detours resulting from repeated surgeries, patients also face significant and demoralizing administrative challenges, such as battling payers to cover care using drugs not indicated by the Food and Drug Administration (FDA) for RRP or deemed “not sufficiently proven.”

The lack of treatment does not mean the RRP community is without hope. They are resilient and courageous and are making meaningful connections through the patient advocacy efforts of the Recurrent Respiratory Papillomatosis Foundation. They are reaching and inspiring researchers at the National Institutes of Health to pursue breakthrough research and oversee clinical trials. They also connect with scientists advancing possible therapies at discovery and clinical-stage biopharmaceutical companies like Precigen and encourage them to move forward by enrolling in clinical trials.

Collaboration Accelerates Change

When people unite, their presence creates energy. The Recurrent Respiratory Papillomatosis Foundation, biotech company Precigen, the National Cancer Institute (NCI), and RRP patients and their caregivers met on June 11th at the National Press Club for the Inaugural International Recurrent Respiratory Papillomatosis Awareness Day. This was an inflection point for those who follow the rare disease category.

The gathering wasn’t about hype or baseless optimism; it was a meeting that brought people together, prepared and ready to roll up their sleeves and get to work. It was a day that reaffirmed a commitment to transparency and a truthful assessment of the current situation and path forward.

Virginia Senator Mark Warner, chair of the powerful Senate Intelligence Committee, which oversees cybersecurity efforts that are key to healthcare and innovation data protection, kicked off RRP Awareness Day by expressing his support for people with rare diseases and his desire to help RRP patients find their voice. Senator Warner stated his desire to advance research and innovation and ensure access to care, an expression of determination that reflected his long-standing record on behalf of people seeking treatment options and improved outcomes.   

RRP Foundation President Kim McClellan also spoke as an advocate for the RRP community and as a patient. “We are here to raise awareness about RRP and bring together critical stakeholders in a dialogue on important aspects impacting individuals living with RRP,” she said. “We invite and encourage anyone living with RRP, either as a patient, family member or caregiver, to join us in spreading the word about RRP and participate in clinical trials and advocacy efforts.”

The date of this groundbreaking gathering has special meaning for the RRP community. June 11th (6/11) corresponds to HPV variants 6 and 11 associated with RRP. As the date symbolizes, the gathering united people with the disease, their family members, congressional leaders, and researchers from government agencies and corporate partners in a community united in a common cause.

The opportunity to share and hear multiple perspectives enriched discussions and underscored the importance of taking a comprehensive approach to tackling this condition. Panels of experts and patients sharing personal stories about their journeys gave attendees an unmatched opportunity to delve into the intricacies and impacts of RRP.

Helen Sabzevari, PhD, President and CEO of Precigen, expressed that she and her company were “proud to join forces with the RRP Foundation to establish the first global RRP Awareness Day to bring visibility to the many challenges experienced by RRP patients and to help forge connections among patients, clinicians and government officials.”

A former NCI team leader, Dr. Sabzevari’s commitment to RRP awareness and patient well-being as an animating principle is a model biopharma company C-Suite executives would be wise to emulate. For her and her Precigen colleagues, patients are the focal point of every decision, action, and investment.

RRP Awareness Day was an inspiring platform for discussing struggle, stigma, and science. Lunch was optional, but tissues were required as attendees in the filled-to-capacity room listened to a patient panel on how RRP impacts people and their families. They learned how some individuals living with RRP have needed hundreds of surgeries over the years, beginning when they were toddlers or young children in primary school.

Culture Drives Clinical Performance

Therapeutic innovations are needed to ensure that future generations living with RRP have options reviewed and indicated by the FDA for treating this viral condition.

During the event, a panel of representatives from advocacy and research reflected on how their collaborative approach centering around patients – from the design of clinical trials to allocating resources that have enabled patients to participate in those trials – has been vital in accelerating the R&D process toward identifying and developing viable treatments. The panel included James Gulley, MD., PhD., NIH, Senior Investigator, Center for Immuno-Oncology, Acting Co-Director, National Cancer Institute/Center for Cancer Research; Scott M. Norberg, DO., NIH, Associate Research Physician, Center for Immuno-Oncology; Helen Sabzevari, PhD, CEO, Precigen; and Kim McClellan, President, RRP Foundation.

Dr. Gulley, who is part of the NCI team and has been instrumental in advancing research on RRP and its connection to HPV, emphasized the pressing need for innovative therapies. In his panel comments, Dr. Gulley highlighted the importance of collaborative research efforts to explore potential immunotherapeutic approaches that could offer new hope for patients suffering from this debilitating condition.

No Disagreement – Harmony

Panelists Gulley, Norberg, and Sabzevari applauded the patient community, acknowledging the courage of their readiness to volunteer to participate in clinical trials to speed possible therapeutics forward. It was a reassuring presence and a reminder that public-private collaborations, particularly for rare diseases, do more than spark hope; they spur action. The patient-panel takeaways were: (1) Connect with the RRP Foundation, (2) Support ongoing clinical trial efforts, (3) Prevention through HPV vaccination is key.

While there is still no FDA-approved treatment to manage RRP, this community remains resilient and upbeat, inspiring everyone facing the challenge of rare conditions. The RRP Foundation, Precigen, and NCI are on the same page—science is essential. People living with RRP can remain hopeful that this collaboration will continue until actions result in better options for this patient community.

The post HPV Urban Legends – From Contagion to Symptoms to Risks to Prevention – There Are More Rare Concerns that Deserve Our Attention appeared first on Medika Life.

Achievements in science, tech advancements, shifts in health policy, a renewed interest in preventative care, and tackling health disparities can shift how we improve people’s health. Will these topics be front and center at HLTH?  We’ll know more in the days ahead. 

10 Predictions for the HLTH Main Stage

Here are my 10 predictions for health innovation in 2024 that have the potential to transform health – topics that should be woven into the commentary during HLTH mainstage conversations – that can make the most significant impact to improve people’s outcomes, reduce costs, and advance wellness. Let’s see what next weeks social media posts provide that give us indication of the changes ahead.

Prediction 1: AI-Driven Medicine Saves Lives

ChatGPT and AI (augmented intelligence) made their big public splash this year!  However, Microsoft and evangelists such as Tom Lawry and John Nosta have been pointing to AI as a life-sustaining tool in health for years. Surprisingly, “big data and “machine learning didn’t attract the same attention as the newest label – AI!  These technologies enable the development of highly personalized treatment plans based on an individual’s genetic makeup, medical history, and lifestyle and risk factors. AI-driven predictive models will assist health providers in making more accurate diagnoses faster and tailoring treatments for optimal patient outcomes.

Prediction 2: Telemedicine and Virtual Patient Monitoring Go Mainstream

Telemedicine saw unprecedented and “no alternative” growth during the COVID-19 pandemic.  It should continue to see prominence in 2024. Improvements in telehealth infrastructure and regulatory support make virtual consultations with health professionals accessible and efficient. One challenge has been reimbursement for providers compared to in-office visits.  There is a time and place for in-person care and virtual engagement.  Regardless, the urgencies of people in rural and remote communities and preventive care needs make telemedicine and virtual patient monitoring public health priorities.  There is no going back!

Prediction 3: Women’s Health Innovation Prioritized

Women’s health remains under-researched and is barely prioritized by biopharma companies and government-supported research grants. Women comprise half the adult population, but research into women’s health needs is embarrassingly low. The National Institutes of Health directs $42 billion on medical research annually, but only $5 billion of those funds are targeted to women’s health priorities. One global company stands out as a leader – more are needed. In the 1990s, women were more likely to die from their first heart attack compared to men due to gender bias. While those statistics have improved, women still face numerous public policy and care disparities – among the more pressing challenges – reproductive choice. These issues should take center stage and HLTH may be the platform for this long over-due (and urgent) conversation.

Prediction 4: Digital Therapeutics Take Center Stage

Digital therapeutics, including smartphone apps and wearables, will become integral to health intervention and connection. These innovative tools help patients manage chronic conditions, monitor vital signs, and adhere to treatment plans. The gamification of health through digital therapeutics will encourage patient engagement and long-term health outcomes.  Sector leaders, like Click Therapeutics Founder David Klein, are adopting “biopharma” like research models to demonstrate their value to patient care by conducting well-designed clinical trials that show complementary benefits with and with other therapies.  Those enterprises will set the stage for the future of digital therapeutics and redefine the category.

Prediction 5: Health Data Privacy and Security

Despite the hype, consumer-friendly cybersecurity technologies can shift how health data is managed and shared. Patients will have greater control over their health information and records, with the ability to securely share them with health providers, clinical researchers and other stakeholders as needed. Data that cannot be accessed or shared transparency and securely is useless in sustaining and saving lives. Consumers and health professionals need easier ways to protect sensitive health information and streamline data exchange for improved care coordination. EMRs are great if they offer convenient use and application; however, they are too often a jumble of inaccessible information. Security and utility are key! So long (hopefully) fax machine!

Prediction 6: Obesity as a Treatable Disease

Among the most dramatic ways to reduce disease burden and address heart disease, diabetes, respiratory illness, and even some cancers is to take obesity (very) seriously.  It Is not only about weight reduction but understanding that obesity is a domino effect, a multi-system disease. Weill Cornell’s Louis J. Aronne, MD‘s pioneering work recognized early that seeing this only as a “weight problem” underestimates its enormous human health impact. More and more, physicians will need to tap into the expertise of specialists to guide their treatment decisions.  With new medications available, physicians will examine the problem and think about solutions.  However, reducing weight is only part of the clinical response.  Getting it right will save millions of lives and billions in costs.

Prediction 7: Robotics and Automation

Don’t be surprised when robotic technology is increasingly integrated into health systems ORs and patient-care wings. Robots will soon perform set surgical procedures, dispensing medication, and performing patient-care tasks. Watch for Rafael Grossmann, MD, who first used Google Glasses in the OR to push the boundaries on what is possible and needed.  Automation will enhance efficiency, reduce human error, and improve patient safety. Robotic exoskeletons will also aid in rehabilitation and mobility for individuals with physical impairments. But remember the human touch!  While ChatGPT has become a patient favorite in searching out information and robotics will transform the patient experience, people’s confidence in skilled medical professionals remains paramount.

Prediction 8: Mental Health Priorities

There is a long-needed shift toward destigmatizing mental health issues and increasing access to mental health services. AI-powered chatbots and virtual therapists will provide on-demand support, while data analytics can identify at-risk individuals and tailor interventions. Virtual reality therapies will increasingly become a mainstream treatment option for anxiety and PTSD.  Services and upskilling are becoming an investment and professional-development priority.  However, while tech has a place in the process, there is something to be said for developing a personal relationship with a licensed psychologist or licensed clinical social worker skilled in face-to-face therapy. It’s always about caring for people!

Prediction 9: Global Collaboration for the Next Pandemic

The COVID-19 pandemic highlighted the importance of global collaboration in addressing public health emergencies. In 2024, international cooperation and data sharing must be at the forefront of pandemic preparedness. A global surveillance network will provide early warning systems, and rapid vaccine development platforms should be established to respond to emerging infectious diseases quickly.  COVID was a test run, and from a public health information standpoint, the developed nations stumbled.  From disappointment comes learning. Collaboration among public health professionals, policymakers, and medical innovators was paramount to the – even stymied – response. 

Prediction 10: Ethical Considerations for Health Innovation

As health innovation advances in 2024, ethical considerations must take prominence. The long overdue pain revealed during COVID must shift mindsets, behaviors and budgets. We must expect increased scrutiny and priority around data privacy, AI bias, health, and attention to racial and gender disparities.  We must set a path for responsible use of emerging technologies. We must recognize that public policy cannot diminish people’s care options. Ethical frameworks and regulations will be developed to ensure that health innovation benefits all people – and all nations – while respecting access, rights, and values.

A Common Call to Action at HLTH

These 10 predictions are a glimpse into the possibilities of what we might hear from speakers during HLTH. AI-driven personalized medicine, telemedicine and virtual patient monitoring, women’s health, digital therapeutics, cybersecurity, obesity management, robotics, mental health innovation, global collaboration, and ethical considerations should be front and center in the conversation to improve people’s health and well-being.  Life is often referred to “as a game.” It’s not. Health access cannot be roulette wheel spin left to chance. It requires advocacy, policy, planning and empathy. Kindness is a human quality that must be given center stage.

Right now, the people who often need preventive and primary care services face the most significant hurdles.  These predictions are based on one underlying principle – health innovation can only achieve its greatest potential when available to those with the greatest needs.  Hopefully, we’ll hear from more and more speakers stepping to the stages at HLTH that shared call to action.

The post When It Comes to the Future of HLTH – Life Is Not a Las Vegas Roulette Wheel appeared first on Medika Life.

CAR T therapy, a “living drug,” traditionally involves isolation and purification of T cells outside the body. The cells are then modified with a synthetic receptor and then re-infused into the body for treatment of cancers. Researchers have now successfully demonstrated that T cells can be modified in vivo by mRNA technology, bypassing the need for extraction, chemotherapy and re-infusion. Although this method proves effective in treating mice with scarred hearts, considering fibrosis contributes to over 800,000 deaths worldwide, the study contains great potential for human treatment.

A Damaged Heart 

The heart, flexible yet strong, circulates blood through the body by pumping blood through its chambers. Aging and injury tamper with this function, creating scarred and thickened tissue called fibrosis. Although fibrosis occurs normally when healing, a highly fibrotic heart loses its elasticity; the stiffened tissues and interrupted electrical signaling prevent proper contractions of the heart (see Figure 1). Cardiac fibrosis is highly associated with heart disease and heart failure.

Cardiac fibrosis has no “cure-all” treatment. Early detection improves prognosis, but options dwindle as damage progresses irreversibly. People with advanced cardiac fibrosis may take drugs which antagonize overstimulation of the heart or might even require heart valve replacement.

How CAR T Cells Work

In their study, Rurik et al. explore a new method to directly counter cardiac fibrosis. This method builds upon the basics of CAR T: the use of T cells with a synthetically engineered receptor to target and kill specific cells.

CAR T is approved to treat people with certain lymphomas, leukemias, and multiple myeloma. Figure 2 illustrates this process. In these cases, the desired T cells are extracted from the patient’s body. Synthetic mRNA is inserted into the cell with a retrovirus, a virus commonly used in gene therapy to permanently change other cells’ genomes. The altered and expanded cells are then infused back into the body after preparatory chemotherapy. These T cells target either CD19 or BCMA, two antigens found on malignant B cells.

The benefit of inserting genetic information with a retrovirus lies in its permanence. The CAR T cells can expand and persist in the body for a long time after infusion, continually fighting the cancerous cells they encounter. However, this is of no benefit to researchers hoping to fight cardiac fibrosis. If T cells continuously target fibrotic cells, they would impair normal healing processes and potentially induce autoimmunity. Rurik et al. employ an elegant solution which shortens the CAR T cells’ active duty, thereby circumventing the extraction process altogether.

 New CAR T Cell Design 

The team adapted mRNA delivery technology seen in current COVID-19 vaccines and applied it to basic Chimeric Antigen Receptor design. The mRNA does not integrate into the T cell genome, allowing for temporary transcription of the mRNA and transient expression of the new receptor.

CD5 Lipid Nanoparticles (LNP) 

The authors adopted a strategy to introduce the chimeric receptor to T cells in the body rather than extracting and purifying them outside the body. To accomplish this aim, they first synthesized mRNA that encodes a receptor against fibroblast activation protein (FAP), a protein expressed on activated fibroblasts responsible for fibrosis. They purified the mRNA and packaged the engineered mRNA into standard lipid nanoparticles (LNP).

The team then decorated the lipid nanoparticle surface with CD5 targeting antibodies to direct lipid uptake. The integration of CD5 antibodies allowed the lipid nanoparticles to target antigen CD5 naturally expressed by T cells once injected into the body; the CAR T cells are made after a single shot.

Chimeric Antigen Receptor 

The chimeric antigen receptor contains a single chain variable fragment (scFv) derived from fibroblast activation protein monoclonal antibodies; this recognition domain enables the CAR T cell to target cells which express fibroblast activation protein. The CAR design also includes CD28 and CD3z signaling domains in the cytoplasm. All three components are mouse-specific. Not illustrated in Figure 3 is an added small peptide which prevents immune suppression.

Genetic Integration In Vivo

The team found that lipid nanoparticles could successfully deliver the mRNA package to T cells, as seen in Figure 4. The killer T cell absorbs the lipid nanoparticle by endocytosis. The lipid particle then degrades and the synthetic mRNA releases into the cell. Finally, the cellular machinery reads the genetic instruction and briefly produces the receptor against fibroblast activation protein. This is possible with both animal and human T cell cultures.

Transitory CAR Expression 

Unlike traditional CAR T cells that carry a chimeric receptor encoded by DNA inserted into the genome, these CD5+ T cells carry mRNA only transiently. The mRNA is not integrated into the cell’s genome and remains stuck in the T cell cytoplasm before degrading. This is ideal; fibroblast activation protein receptors must be expressed briefly as longer expression may harm other tissues.

 Results 

The research team assessed the efficacy of the CAR T cells in different conditions. When they treated the cells in tissue culture, more than 80% of T cells expressed the chimeric antigen receptor and could effectively kill target cells with fibroblast activation protein.

The team then tested this model on mice with cardiac fibrosis. The mice received medication to injure the heart and induce scarring. After one week, the team administered the lipid-mRNA injection. Consistent CAR expression was noted 48 hours after injection, and disappeared after one week.

The results were impressive. The function of the heart’s largest chamber improved, in some cases returning to uninjured levels. Similarly, the amount of blood filling the heart normalized to safe volumes. The therapy notably reduced the thickness of the heart. Finally, although the mass of the largest chamber did not normalize, it trended towards improvement.

One caveat in lipid-CAR T cell delivery is that some cells, perivascular fibroblasts, do not express fibroblast activation protein. In consequence, these cells were not impacted by CAR T cells and some fibrosis persisted. No overly toxic side effects were noted.

Trogocytosis

A key observation of effective CAR T therapy is the ability of the modified T cells to take small bites of the target cell—a phenomenon known as trogocytosis. Deriving “trogo” from the Greek word “to bite,” trogocytosis entails one cell nibbling another and, in the process, transferring the surface molecules from one to the other. The researchers found evidence of CAR T cells “nibbling” the activated fibroblasts and retaining the stolen antigens (illustrated in Figure 5), suggesting that the T cells successfully adopted the chimeric antigen receptors in vivo.

Future Implications

CAR T therapy revolutionized cancer treatment with its efficacy and innovation. Combining mRNA technology to this therapy creates a temporary version of this “living drug” that does not sacrifice on quality. The therapy is well tailored to heal mice with damaged and scarred hearts, and widens the possibilities to treat other non-cancerous human ailments. If translated to clinical settings, transient CAR T therapy may be less expensive and more readily available than its traditional counterpart

The post CAR T-mRNA Therapy For Cardiac Fibrosis: A New Way Forward appeared first on Medika Life.

Particularly now, when it looks increasing likely that the Wuhan Institute of Virology and their GOF research (US funded) on coronaviruses led to this pandemic. Even the ex-CDC Director has come out in favor of the lab leak theory. So, is this a good idea?

Can I Get a NO? A Loud, Resounding, Absolute NO.

Not in any rational, sane world that is intent on survival of the species, can we permit the continuance of this kind of research in its current form. Especially in the kinds of laboratories we currently use, where apparently, upgrading the walls to Swiss cheese would offer better protection than is currently available. Especially in the hands of scientists, politicians, media and a pharmaceutical industry all of whom have just schooled us on how to manipulate the human race.

How many millions more may pay with their lives for the greed, avarice or incompetence of the few? We haven’t yet held these individuals to account for the 2019 pandemic and here we are again, back on the roundabout, hell bent on laying the groundwork for a second one.

And that is really where the problem lies. It isn’t the science that’s flawed. GOF is a really useful tool, but like the most deadly assault rifle, it can be used for protection or for mass extinction. It depends on the hand that wields it and science has been coopted by individuals and companies that look only to profit and the pursuits of their political masters. In the process, we die, by the millions.

To depress you even further, we cannot walk this back. Not ever. The gene-manipulating genie is out of the bottle and there’s no putting it back. This type of research will still continue, even if it is outlawed at the highest levels. The potential rewards, which are huge, far outweigh the risks. The only solution is to manage it, somehow.

How Do We Fix This?

Elon, so glad you stopped by, as you, or a group of individuals (we understand not everyone can buy the bluebird of happiness on a whim) may very well hold the key to our continued existence, and no, I am not suggesting relocating Pfizer, Moderna and the rest of their motley crew doing pathogen research to Mars, although I’d probably chip in myself for the rocket fuel for that trip.

We know that the current logistical management for GOF needs to be better. Unfortunately, we cannot contain the viruses we work on safely within a facility without them escaping; even our highest levels of security, BSL4 labs, are breached. Every year, incidents occur across the globe, and we may even have the next potential pandemic underway as I write, that is how frequently it happens.

Logic dictates we either stop the practice (not happening) or take steps to ensure we don’t kill the entire global population, unintentionally, or otherwise. To do this, it is critical we remove the danger from populated areas.

We need to establish a global research facility, one of a kind, independently monitored and audited, that is as far removed from proximity to humanity as possible. The middle of the desert springs to mind, a dedicated center for viral research where, in the event of a breach, only the unfortunate scientists pay the price for their carelessness.

To overcome the strain of lengthy periods of isolation, a facility constructed for these purposes could be expanded to include schooling and retail therapy, allowing scientists to pursue their passions and research in a semblance of normality. Most of the pioneers and researchers engaged in Gain of Function are driven by the science, they are passionate and focused, and again, it is their work that is co-opted, rarely the individual.

Quarantines would apply to all personnel leaving the facility, requiring a five-day plus furlough in a Trump Hotel built five miles away. Driverless Teslas, repurposed for deliveries, would alleviate the need for contact with the outside world, and Elon, you could use this as a dry run for Mars.

Humor aside though, the idea has merit and may very well offer a way out of our current predicament. The only other viable alternative is to temporarily halt all research until we are able to fully automate facilities handling dangerous viruses. By that, I mean no human interaction at all. Experiments could be performed remotely, utilizing robotics. We are technically capable of this, but it would be incredibly expensive (I wonder who has a few billion in pandemic profits lying around), restricting who would be able to utilize this kind of technology.

Great Kindness or Greed? We All Hope the Former

Humans are capable of great kindness and innovation, but the danger with this type of research always defaults to the involvement of the human element. We are prone to making mistakes, ask all the unfortunate and very dead researchers working with these pathogens when they escape. Realistically, if safety is our paramount concern, and it should be, our only viable option is to remove GOF research from its proximity to our populations. Back to option 1.

This discussion is unfolding right now, preempted by the letter I referred to above. Perhaps the logic here was to get their case heard before all the wheels come off. When evidence surfaces, and it will, to corroborate the lab leak theory for the SARS virus, all bets will be off. The backlash will be spectacular and science, unfortunately will pay the price. Science we desperately need to cure the ills that have been ailing us for generations.

Villagers and their torches aren’t particular about what they set fire to, and in this instance, they have good cause and science will burn.

Any solution that removes the risk of exposure to pathogens from accidental spillage, cannot obviously account for nefarious intentions, sadly something the industry is rife with. Another thorn in the side of ethical science that needs to be overcome and security at this remote facility would need to be ironclad.

GOF Can Result in Life-Saving Drugs or Danger

We’d like to spark a proper conversation on this subject, involving people who have the resources (Elon, you still here?) to implement solutions that are in the interest of both science and public safety. The two parties must find a way to safely coexist.

It is also worth mentioning that gain of function is far more than what the public perceives it to be. The technology is critical to developing new drugs, new cancer treatments and many other practical uses that do not focus on weaponizing pathogens. Making a virus more deadly may utilize Gain of Function technology, but it represents only a fraction of the industry’s use of the technology.

If you have thoughts on the matter or would like to publish something relating to this, please feel free to reach out to Medika Life via DMs on Twitter. You’ll find us hugely receptive.

The post Elon Musk, Can You Save Us From Covid 2.0? appeared first on Medika Life.

This third installment highlights recent advances in treating multiple myeloma. The first in the series lays the foundation for understanding how CAR T works, while the second outlines its uses for B cell cancers.

Multiple myeloma is a relatively uncommon yet serious disease estimated to impact more than 30,000 US citizens this year. Although several treatment options exist, the illness is considered incurable as most treatments do not resolve the condition permanently—including the most recent advancements with CAR T cells. Here, we describe an approach using a different variant of CAR T cells for multiple myeloma that holds promise for those with treatment-resistant forms of the disease.

What is Multiple Myeloma?

Multiple myeloma (MM) or myeloma is a cancer of the plasma B cells found in the bone marrow. Although these white blood cells typically produce antibodies, for people with multiple myeloma, the plasma cells multiply faster than the body can handle, produce abnormal antibodies, and set the body out of balance. The illness can spread to other organs through the bloodstream, and masses of plasma cells may form in the bone marrow or soft tissues, as well.

The illness usually occurs to people 60 years and older, and is unlikely to develop in individuals under 40 years of age. The symptoms can be widely varying—some even report having no symptoms at all—but most with this disease experience bone pain and fatigue. Other common complications include anemia, kidney problems, or thickened blood.

Without treatment, the prognosis is poor. However, with the advent of chemotherapy and more advanced medicines, survival is usually four to five years. If diagnosed early, the five-year survival rate exceeds 77%.

Patients with active myeloma first receive a combination of drugs to target the abnormal cells. Another alternative is chemotherapy. For example, I contributed to the creation of Velcade, a chemotherapy medicine which slows or stops the growth of myeloma cells. Stem cell transplants, steroids and even CAR T therapy—a newer medical technology which alters patient cells in the lab and infuses them back into the body to fight the cancer—may be tried as other potential options. Unfortunately, once a therapy fails, the body typically becomes resistant to its reintroduction and thus loses efficacy.

The Current Reality of CAR T Therapy 

CAR T therapy has recently been approved to treat multiple myeloma, but it is only considered after four or more refractory lines of treatment—in other words, when other four or more options fail to achieve lasting remission. The two existing CAR T therapies on the market target B cell maturation antigen (BCMA), an antigen expressed on the surface of malignant plasma cells; in this piece, the antigen will be referred to as Target 1.

A Chimeric Antigen Receptor T cell derives its name from the synthetic combination of T cell and antibody properties. Patient T cells are taken from the body and modified to detect Target 1 through an antibody-based fusion receptor (scFv). The lysing process relies on signaling from the T cell. As seen in Figure 1, when the CAR T antigen receptor binds with Target 1 on the cancer cell, the CAR T cell releases chemicals to trigger the cancer cell’s death.

Clinical trials have confirmed these CAR T therapies as safe to use and capable of producing results. A study of Ide-cel found 73% of participants had a decrease in their cancer. Even more successfully, a study of Cilta-cel saw a 98% response rate, with 78% of patients showing no signs of cancer in their bone marrow. The outstanding issue with both treatments, however, is that relapse does eventually occur—around 8.8 months later for Ide-cel, and 22 months later with Cilta-cel.

With relapse and treatment resistance a prevailing concern for multiple myeloma treatments—not just CAR T—researchers are seeking new ways to sustain longer remission and increase survivability when other alternatives are exhausted.  One possible method is to enhance current CAR T protocols with a new therapeutic target.

Methods 

In their study, Mailankody et al. consider the safety of an alternative antigen target. The target is known as G protein-coupled receptor, class C, group 5, member D (GPRC5D), but shall be referred to as Target 2 for simplicity. Despite its unknown function in tissues, it poses as a promising CAR T antigen target due to its presence in several myeloma cell lines and in bone marrow plasma cells.

The team chose a second generation CAR T design for their product. Second generation CAR T cells contain a single costimulatory domain (shown in blue in Figure 2) inside the T cell to extend the life of the cell once in the body. The chimeric antigen receptor in this study is tailored to find cancer cells that express Target 2 (denoted in green in Figure 2).

As depicted in Figure 3, the researchers first collected patient T cells through leukapheresis. They modified the T cells, expanded them to large numbers, and then infused the CAR T cells back into the body after completing preparatory chemotherapy. The patients received an escalating dose of the trial CAR T infusion, totalling to four doses.

Results 

A total of 17 participants received CAR T therapy, all who have previously tried five different kinds of multiple myeloma treatment. The majority of participants developed cancer resistance to their last line of treatment; this includes a group of individuals who previously received Target 1 CAR T therapy.

On the whole, this study successfully confirms Target 2 CAR T therapy as safe and effective, particularly for individuals who have already received Target 1 CAR T cell therapy or have run through several other therapeutic options. Around 78% of patients had a partial response or better, and 59% had a very good partial response or better. The therapy was effective even ten months after infusion for some individuals.

Common CAR T therapy side effects include cytokine release syndrome and immune effector cell-associated neurotoxicity (ICANS). While both conditions can be reversed with prompt treatment, the severity of both side effects can range from mild to life-threatening. Most participants experienced milder cytokine release, with the exception of one patient who experienced life-threatening side effects. All with side effects were treated.

Future Directions

Mailankody et al. demonstrate that Target 2 CAR T therapy can effectively treat multiple myeloma. If Target 1 CAR T therapy fails, Target 2 appears to be a viable alternative. The results also suggest that using Target 1 and Target 2 CAR T therapies in succession could lead to positive outcomes. A third alternative is to enhance the T cell design further to allow for tandem targeting; an ideal synergy could be attained if T cells were fitted with both Target 1 and Target 2 receptors, hopefully resulting in longer remission periods and increased survival.

The post CAR T Therapy For Drug Resistant Multiple Myeloma appeared first on Medika Life.

Using the body’s own immune cells as anticancer agents has long been part of this dream. I was an early pioneer in creating one of the first proven cell therapies using dendritic macrophages to treat prostate cancer. Today, immune cell therapy offers hope to people with cancer and other previously untreatable diseases.

This series will explain a recent and revolutionary cell therapy called CAR T, delving into current successes and future opportunities.

The “T’ of CAR “T” 

CAR T is short for Chimeric Antigen Receptor T cells. Essential to understanding this therapy is an understanding of T cells and cell-mediated immunity.

Adaptive Immunity 

Adaptive immunity allows humans to form a tailored defense to foreign invaders. Adaptive immune cells memorize the telltale signs of enemies and trigger defensive mechanisms if the signs are detected in the future. This branch of immunity concerts two separate arms—humoral immunity driven by antibody-producing B cells, and cell-mediated immunity driven by “helper” T cells and “killer” T cells.

CAR T technology alters the typical functioning of cytotoxic cells. Instead of indirectly aiding antiviral processes as CD4+ helper T cells do, CAR T borrows the cytotoxic power of CD8+ killer T cells to destroy infected or abnormal host cells, thus transforming into a “living drug.” A typical cytotoxic T cell eliminates threats using the following process:

WIKIPEDIA Link Added

The process (as illustrated in Figure 1) begins with the differentiation of an inactive T cell—in essence, any T cell without a specified purpose. As if waiting for the right key, a T cell does not activate unless it encounters an antigen presenting cell (APC) with its corresponding antigen. In order for an interaction between the two cells to occur, several steps must occur.

Firstly, the antigen presenting cell must process the antigen, the enemy components, into smaller peptides. Then, these peptides must be carried to the antigen presenting cell’s surface by major histocompatibility complexes (MHC). Immature CD8+ T cells require MHC Class I molecules to facilitate this translocation. Around this time, a secondary signal such as CD80 or CD86 must also be received by the T cell. In the final step, the antigen presenting cell releases a protein signal called CD40 and cooperates with helper T cells to finalize the differentiation process.

How Killer T Cells Kill 

DANANGUYEN DERIVATIVE: NAGUALDESIGN

Killer T cells destroy infected and abnormal cells by inducing apoptosis, a form of controlled cell death which does not spark inflammation. Pockets of enzyme within the T cell must make contact with the target cell to trigger its death.

When a cytotoxic T cell recognizes its target, it binds to the class I MHC molecule on the surface of the target cell (see Figure 3) to create a bridge. With the bridge completed, the T cell can then release the enzymes. One enzyme drills pores in the target cell’s membrane, thus ruining its integrity. The other travels through these newly made tunnels, tipping an enzyme cascade inside the target cell which accelerates its degradation.

The crumbling target cell mimics the imagery of bricks falling from castle walls. Nearby phagocytes recognize the “crash of bricks”—more accurately, sense a change in membrane—and begin ingesting the target cell. The target cell breaks down to nothing inside the phagocyte without stimulating inflammation or other side effects.

Construction of a Chimeric Antigen Receptor 

Killer T cells are clearly useful in clearing irregular host cells. Researchers recognized this and sought to harness this natural design to eliminate cancer cells through CAR T. Chimeric antigen receptors are engineered to detect a specific antigen and trigger the destruction of a target cell. The most basic CAR T design accomplishes this by manipulating antigen binding sites normally intrinsic to antibodies—single chain variable fragments (scFV)—to lend cytotoxic T cells higher antigen specificity. The CAR T cell recognizes specific antigens thanks to this domain.

Next comes the flexible hinge region. This region simultaneously stabilizes the CAR while its length provides grants easier access to specific antigens. The transmembrane domain anchors the antibody and hinge structure.

The intracellular domain describes receptors lying within the T cell. Basic CAR T design employs CD3 here, a T cell receptor needed for T cell differentiation (see Figure 4). Second and third generation CAR models included secondary signal receptors such as CD28 to improve target cell elimination and cell signaling (Figure 5).

More recent research developments in CAR design deviate from this foundational model to finetune precision and function. For example, T cell receptor fusion construct (TRuC) CAR tethers the scFV region to the several intracellular CD3 subunits, thereby reducing secondary signaling hypothesized to be unnecessary.

Universal CAR (uCAR), on the other hand, augments antibody specification by fusing biotin to the transmembrane domain and the endodomain. Other research efforts incorporate cytokines (signaling molecules) and other molecules to improve T cell expansion and persistence, as well as synthetic control switches to minimize the therapy’s toxic side effects. The groundwork model inspires many alternative CAR designs beyond those demonstrated here.

The beauty of this science lies in the melding of two previously separate abilities. CAR T therapy replaces the T cell receptor with an antibody-like structure, all while maintaining the transduction machinery of a T cell. Like this, MHC class I binding becomes irrelevant and a response can be immediately triggered.

The CAR T Therapy Process 

What does the CAR T therapy process look like?

Figure 2 illustrates the progression clearly. For a patient receiving CAR T therapy, the process may begin with a medical professional drawing their blood and separating T cells from that sample using apheresis; this would be an autologous treatment, as the cells used originate from the same patient. T cells can also be isolated from a healthy donor’s blood sample, otherwise known as allogeneic transplantation.

The cells must then be genetically altered to recognize a particular target in a cell processing center. To do this, the cells are “expanded”—a process which stimulates T cell proliferation. The new plethora of T cells must be purified and then genetically modified with a gene that encodes the desired chimeric antigen receptor. CRISPR technology can be used here to accomplish the task.

The cells are now ready for infusion. The cells are frozen and sent back to the treatment center. The patient preps for infusion with a lymphocyte-depleting chemotherapy; the chemotherapy reduces the number of white blood cells in the blood to reduce competition for the CAR T cells, thus helping them multiply. With success, the engineered T cells will recognize the antigen on cancerous cells, bind to it, and mark it for destruction via apoptosis. The infusion takes between 30 to 90 minutes to complete, but the patient will be closely monitored for days, weeks or months to watch for any adverse side effects and to receive additional treatments.

Side effects can occur if the “living drug” multiplies too actively, the most common being cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Also commonly known as “cytokine storm,” CRS occurs when proteins called cytokines flood the immune system and send it into overdrive. Symptoms tend to be mild—fever, nausea, headache, rash, and more—and resolve within a couple of days, but they can also be severe or life threatening. ICANS refers to a neurotoxic condition that appears within one to three weeks after T cell infusion. Early signs, such as tremor and lethargy, can lapse into stupor, seizures or coma if untreated. More on managing side effects to come in later installments in this series.

The long term side effects of CAR T are unknown. As a result, the FDA stipulates that gene editing treatments such as CAR T therapy should be monitored for up to 15 years—five years of annual follow ups, followed by ten years of questionnaires and/or other queries.

What Illnesses Can CAR T Treat?

CAR T therapy is FDA approved to treat B cell-derived lymphomas—cancers caused when B cells (not T cells) grow too rapidly—as well as multiple myeloma, cancer of plasma cells found in the bone marrow. These treatments tailor chimeric antigen receptors to target an antigen called CD19 found only on the tumor cells of lymphoma patients. Another target is BCMA, a B cell maturation antigen specific to multiple myeloma.

CAR T therapies may be federally approved, but they are not used as first or second line cancer treatments; usually CAR T therapy is considered after receiving standard chemotherapy treatment and other alternatives. And as a newer treatment, it may be more expensive than other therapies or may not be fully covered by health insurance.

But this field is ever growing. Several hundred clinical trials are in progress to test the boundaries of this mechanism and enhance its design. The next installations in this series will cover some of the most recent discoveries in the CAR T circuit, such as treatment advances in B cell lymphomas, lupus and heart disease, as well as innovations in CAR T precision.

The post From Lymphoma To Lupus And Beyond: The Remarkable Research Of CAR T Therapy appeared first on Medika Life.

Almost exactly 100 years ago in 1920, hot on the heels of the discovery of x-rays by German scientist Wilhelm Conrad Röntgen, a new machine was introduced into shoe shops across the globe. Called the Fluoroscope or Pedosscope(UK) the device was essentially a portable x-ray machine with a singular and rather ingenious purpose.

The idea was brilliant. Customers could try on a new pair of shoes and pop their freshly shod feet into the Fluoroscope box. The device would then produce an x-ray image of your feet inside the shoes. People were obviously fascinated by the technology and the novelty aspect of the machine made it an overnight winner. After all, no one wants to buy shoes that don’t fit properly. An estimated 10,000 machines were sold in the US, 3,000 in the UK, 1,500 in Switzerland, and 1,000 in Canada before authorities began discouraging their use.

Today we know the dangers of continued exposure to x-rays. In the 1920’s we didn’t. What we had instead, in the 1920s, was a new breakthrough in technology that we bravely (foolishly) embraced with little or no concern for the wider safety implications of the technology. If history is anything to go by, the lessons we should have learned from the Fluoroscope and numerous other then-emergent technologies which now litter scientific literature, were lost. 

Even after the dangers of the Fluoroscope and exposure to radiation were highlighted, the devices persisted in many shoe shops in the US until the mid-1970s, with many choosing to ignore the health warnings associated with prolonged exposure to x-rays. To this day, shoe companies deny any liability for the introduction of the machines.

In reality though, how dangerous was the Fluoroscope? This breakdown of the radiation provided by the devices, courtesy of Wikipedia, offers some insight.

Large variations in dose were possible depending on the machine design, displacement of the shielding materials, and the time and frequency of use. Radiation surveys showed that American machines delivered an average of 13 roentgen (r) (roughly 0.13 sievert (Sv) of equivalent dose in modern units) to the customer’s feet during a typical 20-second viewing, with one capable of delivering 116 r (~1 Sv) in 20 seconds. British Pedoscopes were about ten times less powerful. A customer might try several shoes in a day, or return several times in a year, and radiation dose effects may be cumulative. 

For perspective, a dose of 300 r can cause growth disturbance in a child, and 600 r can cause erythema in an adult. Hands and feet are fortunately relatively resistant to other forms of radiation damage, such as carcinogenesis, but spare a thought for the operators of these devices who were effectively exposed to massive doses of daily radiation.

What does this have to with my DNA?

Great question and if you haven’t joined the dots yet, allow me. Science has been seriously experimenting with DNA-based medications for well over a decade and in many ways, these medicines are seen as a holy grail by the medical community. With good reason. Many diseases stem from gene combinations gone wrong and our ability to deliver treatment at this level will quite literally revolutionize medicine.

Identifying and isolating faulty genes and our ability to turn on or turn off switches in our genetic coding could mean the end of many diseases we have been previously unable to treat effectively. Most promising in the emergent field of DNA-based medicines is the ability of science to produce treatments specific to an individual. No more hit and miss, but something that’s been built and designed just for you. A treatment that can be deployed within a few days, and that, most importantly, is cost-effective. 

In the above scenario, the patient is the clear beneficiary. Covid accelerated the development and deployment of exactly these types of medicine. mRNA vaccines deliver nano-particle encapsulated genetic instructions directly to our cells. For many patients with co-morbidities and the aged, these vaccines were, and remain, a god-send. 

There is however a need to embrace our newfound mastery of the body’s DNA with extreme and urgent caution. Unlike the Fluorscope that may have caused cancerous lesions in a few feet and rendered a few operators barren, DNA is universal and our current understanding of the technology and its encompassing risks rival that of the early x-ray. We are at the dawn of new technology, and if history has taught us anything, circumspection and caution are called for.

Currently, there are no DNA overlords. There is no national or global oversight of the impacts of these medicines on us, no specific guidelines, or rigorous safety mechanisms to ensure that we are not exposed to the devastating side effects of future treatments gone wrong. 

As of now, we are celebrating our initial medical successes and as I write this, new medications are being prepared or have already been released into the market. Medicines that target our cell structures and DNA and as with the Fluoroscope, we are assured the whole process is completely safe. In fact, why not get your child to try it out? 

I for one, would rather my child were barefoot for a while.

The post The Fluoroscope Serves as a Warning for New Medical Technology appeared first on Medika Life.

From evolution to the industrial revolution, this is a recurrent theme for humanity and all life on earth. We receive a kick in the ass and move (sometimes crying and screaming) into the future. Sometimes, it’s a singular event that drives a profound transformation—remember those dinosaurs and that asteroid?  And if you use your imagination, you might even see that horrific sphere in the sky and conger some images of the COVID-19 virus. Sometimes it’s a cluster catastrophic events or a confluence of magical things. 

Change is disruptive.  But adoption is gradual.  And that where people get confused.

The year 2021 was certainly disruptive.  And it was defined by COVID-19 and void of innovation that perfectly reflected the difference between disruption and adoption. Certainly, there were important breakthroughs including therapeutics and vaccinations.  But failure was also a defining aspect of a tumultuous year. Adoption can drag its feet…

Clinical uncertainty was met with the demands of rapid action and resulted in the complexities of innovation, confusion, and adoption. COVID-19 compressed years of science, pharmaceutical development, technological advances and clinical practice into just months—sometimes even days. And then, layered moral imperative of action into this equation. The lessons learned from 2021 are vast. But, in many instances, these lessons were driven by events, or, if I may, singularities that helped shape and drive action.

It seemed that almost every day in the past year provided new data, insights, and guidelines that helped informed clinical practice. Yet, this pushed clinicians away from the “clinical comfort zone” into more a “risk/reward” posture where conformation was either antidotal, pre-published, or driven by societal and political pressures. Consensus—from patient to clinician—was sometimes difficult to find. But bravery, from thought to deed, was frequently at hand.

Today, we are around the corner from another asteroid or spike protein.  But we are also at the center of another confluence that offers the potential to transform and protect humanity from those fireballs in the sky.

Social need, technology, genomics, artificial intelligence and a host of factors are aligned for more than a change, but a tectonic shift of unimaginable proportions. These are coming at us with the jolt of disruptive transformative that can make us cling to a safer and more predictable past. But that’s the nature of transformation.  It’s sudden and shocking.  But the human side of that journey may not always align. 

The traditional vision of our future and of transformation is our desire for  “the same but better.”  From the emergence of the electric car (a transition) to the introduction of a new beta-lactam antibiotic with better tolerability and spectrum of coverage (another transition), we adopt in baby steps.  But technology can often loom larger and step more broadly. 

That’s where we are today.  Look up and you’ll see it.  We are just heartbeats from our next inflection point. The question isn’t only about the wonder of technology to help solve these conflicts, but the bravery of humanity to move forward.

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