Using Existing Drugs in New Ways to Treat & Cure Diseases of Brain & Body | Dr. David Fajgenbaum

Diagnosis with Castleman's Disease

Dr. Fajgenbaum's story begins with a harrowing diagnosis in the prime of his young adulthood. A medical student with a background in athletics, he was abruptly struck by a mysterious illness that rapidly incapacitated him, leading to multi-organ failure and multiple near-death experiences. Initially thought to have lymphoma, his condition was eventually diagnosed as Castleman's disease, a rare and complex lymphoproliferative disorder characterized by excessive immune activation causing systemic damage.

The severity of Dr. Fajgenbaum's condition forced relentless treatments, including aggressive chemotherapies and experimental drugs, but each provided only temporary reprieve. His survival depended on an extraordinary inner resolve—a drive cultivated through years of athletic discipline and deeply motivating personal experiences—especially the loss of his mother to brain cancer. That resilience powered his quest to understand and ultimately help others with similar devastating diseases.

The Challenge of Drug Repurposing

Central to Dr. Fajgenbaum's mission is the idea that the solutions to many diseases already exist within the thousands of drugs currently approved for various conditions. The fundamental problem, however, is that the medical and pharmaceutical systems are not structured to systematically explore or validate these alternative uses. Instead, the traditional focus remains on developing new drugs, often with prohibitively high costs and long timelines.

Dr. Fajgenbaum argues that millions of patients are potentially missing out on treatments because approved drugs, which may influence multiple biological pathways, are limited in their "official" uses due to patent issues, lack of incentives, or fragmented scientific knowledge. He advocates for a comprehensive, data-driven approach to matching existing medications to diseases beyond their original indications, effectively accelerating new therapeutic options without the need for entirely new drug development.

Multi-Pathway Effects of Drugs

An illuminating facet of the conversation reveals how many drugs affect a wide array of biological targets—far beyond the singular function for which they were approved and marketed. A typical small molecule drug can bind two to three dozen proteins in the human body, producing a variety of effects, some beneficial and others traditionally considered side effects.

Dr. Fajgenbaum highlights the inconsistencies in how drug effects are categorized. Unexpected positive impacts (formerly considered side effects) remain under-explored, whereas adverse effects receive much more attention. Recognizing and harnessing these multi-pathway effects could revolutionize treatment strategies. For instance, aspirin, while long known as a pain reliever, also reduces the risk of heart attacks and colon cancer recurrence due to its multiple effects on blood flow and inflammation.

The Role of AI

To address the immense complexity of connecting thousands of drugs to thousands of diseases, Dr. Fajgenbaum employs advanced artificial intelligence (AI) technologies, particularly biomedical knowledge graphs. These AI tools aggregate vast amounts of public and proprietary data—scientific publications, clinical trial results, molecular pathways—to identify promising drug-disease matches.

This AI-driven approach allows prioritization of which drugs might be effective for which conditions based on patterns in biology and clinical data, guiding laboratory and clinical validation. This systematic, "everything versus everything" strategy represents a significant departure from the traditional, slow, and siloed drug development process, offering hope that previously overlooked therapies may become accessible to patients who need them.

The Pharmaceutical Patent System

The discussion delves into how economics and intellectual property laws shape the trajectory of drug development and approval. Pharmaceutical companies have incentives to extend patents by finding new uses for drugs within their existing disease spaces rather than exploring entirely new disease indications due to the financial risks involved.

Once a drug becomes generic and inexpensive, interest in repurposing or re-evaluating its potential drastically diminishes because the economic return on investment is limited. This situation contributes to therapeutic stagnation despite scientific opportunities. Dr. Fajgenbaum stresses that this reality explains why many inexpensive, generic drugs with great potential remain underutilized or ignored in clinical practice.

Patient and Physician Agency

A recurring theme in the conversation is the necessity of empowering patients and doctors alike with knowledge and collaborative networks. Doctors, while highly trained and well-intentioned, often lack the time, resources, or incentives to continuously survey emerging science broadly across all diseases and drugs. Consequently, patients often remain unaware of alternative treatment possibilities.

Dr. Fajgenbaum urges patients to engage proactively: identifying and connecting with disease advocacy organizations, seeking out medical experts specializing in their condition, asking persistent and informed questions, and becoming collaborators in their care. This heightened agency may open doors to novel treatments and foster more dynamic dialogues between patients and healthcare providers.

Drug Repurposing Success Stories

Throughout the discussion, multiple compelling cases illustrate the power of repurposed drugs. For example, lidocaine—a common local anesthetic used in dental and surgical procedures—has been shown in a large randomized trial to reduce mortality by nearly 30% when administered before breast cancer surgery. Despite the low cost and broad safety profile, its widespread adoption remains limited.

Similarly, the immunotherapy drug pembrolizumab, initially developed for melanoma, was successfully used to induce durable remission in angiosarcoma, a rare and fatal cancer, long before it became a standard treatment for that condition. Other examples involve TNF inhibitors in rare stroke-causing diseases and drugs designed for multiple myeloma helping patients with related cancers. These cases exemplify the untapped potential of existing drugs when viewed through the correct scientific lens.

Off-Label Drug Use

A nuanced discussion emerges around the risks and ethical considerations inherent in using existing drugs for new indications before wide clinical validation. While desperate patients may pursue "Hail Mary" treatments with off-label applications, such use carries uncertainty, potential side effects, and liability risks.

Dr. Fajgenbaum advocates for rigorous, stepwise processes involving laboratory studies, observational data analyses, and clinical trials to validate new uses responsibly. Collaboration with prescribing physicians and clear patient education are vital to minimize harm. This framework helps balance hope and safety, ensuring that novel applications are more than anecdotal and can become part of reliable medical practice.

Supplements, and Natural Products

The conversation explores the blurry divide between pharmaceuticals and natural supplements, highlighting how many drugs originate from naturally occurring molecules found in plants, soil, or microbial sources—a process known as bioprospecting. Rapamycin, for example, a powerful immunosuppressant drug that Dr. Fajgenbaum takes, was discovered from bacteria found in soil from Easter Island.

He stresses that many substances with perceived "natural" origins or supplements—like nicotine or creatine—also have clinically recognized biological effects, which may be beneficial or harmful. The key lies in rigorous investigation and dosage control. This underscores the importance of scientific validation for both medicinal and supplemental compounds in supporting health or mitigating disease.

Resilience, and Hope

Beyond the scientific and medical content, the podcast touches on neurobiological underpinnings of resilience and motivation using the example of the anterior midcingulate cortex. Research shows that this brain area is a critical hub for sustaining effort and perseverance in the face of challenges by driving the will to "lean into" difficulty.

This mechanism resonates profoundly with Dr. Fajgenbaum's personal story—his capacity to endure repeated life-threatening episodes and maintain focus on recovery reflects this neural circuitry. Clinically, fostering hope and actionable goals can activate such brain networks, underpinning psychological strength crucial for patients navigating serious illness.

Access to Knowledge and Treatments

A major insight is the existing randomness and inequity in how patients access cutting-edge treatments. Only a fortunate few with the right connections, resources, or knowledge gain access to novel therapies or off-label uses. Dr. Fajgenbaum calls for the creation of comprehensive, accessible, and dynamic databases that integrate patient symptoms, familial history, drug data, clinical trial results, and expert networks.

Such platforms, potentially powered by AI and linked directly to patient and physician users, could transform healthcare by standardizing and democratizing access to state-of-the-art treatment options. This would reduce the lottery nature of healthcare outcomes and ensure that promising therapies reach those who need them most, independent of geography or socioeconomic status.

Future Directions

Dr. Fajgenbaum's work culminates in the establishment of Every Cure, a nonprofit organization dedicated to discovering and validating drug repurposing opportunities. By combining AI-driven data mining, laboratory science, clinical research, and community engagement, Every Cure strives to systematically open new therapeutic avenues for a broad spectrum of diseases.

The organization invites participation not only from patients and families seeking hope but also from medical experts, researchers, and donors. Contributing to this collaborative ecosystem is positioned as a critical step toward transforming the paradigm of medicine from isolated efforts to a truly integrated drug repurposing movement with the potential to save millions of lives.