Using Existing Drugs in New Ways to Treat & Cure Diseases of Brain & Body | Dr. David Fajgenbaum
In this episode of the Huberman Lab podcast, Dr. David Fajgenbaum of the University of Pennsylvania discusses how existing FDA-approved drugs can be repurposed to treat rare and seemingly untreatable diseases. Drawing from his personal experience with Castleman's disease, Fajgenbaum explains the challenges of investigating new uses for generic drugs and describes how his organizations work to identify alternative applications for existing medications.
Through his work with the Castleman's Disease Collaborative Network and EveryCure, Fajgenbaum shares how AI technology is being used to analyze thousands of FDA-approved drugs against human diseases. The discussion covers specific examples of successful drug repurposing, including treatments for Castleman's disease and DADA2, while exploring the potential of various medications to prevent or treat conditions like heart disease, cancer, and neurodegenerative disorders.
This is a preview of the Shortform summary of the Nov 3, 2025 episode of the Huberman Lab
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1-Page Summary
Repurposing Existing Drugs to Treat "Untreatable" Diseases
David Fajgenbaum, a professor at the University of Pennsylvania, discusses how existing FDA-approved drugs can be repurposed to treat rare and seemingly untreatable diseases. Drawing from his personal battle with Castleman's disease, Fajgenbaum emphasizes that patients should actively seek out disease organizations and expert physicians who might know about off-label drug applications, as the medical system isn't structured to discover new uses for existing medications.
Systematic Approach to Drug Repurposing
Through his organizations, the Castleman's Disease Collaborative Network and EveryCure, Fajgenbaum has identified 14 drugs that can treat diseases they weren't originally intended for. Notable examples include [restricted term] for Castleman's disease and TNF inhibitors for children with DADA2. Fajgenbaum advocates for a more collaborative medical research model, suggesting that labs should be named after the issues they aim to solve rather than individual investigators.
The Challenge of Generic Drugs
Fajgenbaum and Huberman explain that once drugs become generic, companies have little financial incentive to research new applications, despite their potential. For instance, [restricted term] shows promise in reducing heart disease risk, and lidocaine could reduce mortality during breast cancer surgery, but their adoption for these uses has been limited due to lack of commercial interest. In response, Fajgenbaum's nonprofit EveryCure works to identify and promote new applications for existing medicines without profit motives.
Preventative Health Applications
Many drugs have untapped potential beyond their original uses. Fajgenbaum shares his success with [restricted term], while Huberman relays insights about nicotine's potential protective effects against neurodegenerative diseases. They also discuss emerging evidence about GLP-1 agonists showing promise in treating Parkinson's and reducing Alzheimer's risk.
AI-Driven Drug Repurposing
Through EveryCure, Fajgenbaum is leveraging AI to analyze 4,000 FDA-approved drugs against 18,000 human diseases. This systematic approach has already yielded success, such as identifying a TNF inhibitor for Castleman's disease. The organization continues to use AI to accelerate the discovery of new applications for existing drugs, potentially offering hope for patients with urgent medical needs.
1-Page Summary
Additional Materials
Clarifications
- Off-label drug applications involve using medications for purposes other than those approved by regulatory agencies like the FDA. This practice is legal and common in medicine but requires careful consideration of risks and benefits by healthcare providers. Patients may benefit from off-label use when traditional treatments are ineffective or unavailable. Healthcare providers must stay informed about emerging research and guidelines to make informed decisions about off-label drug use.
- TNF inhibitors are pharmaceutical drugs that target tumor necrosis factor, a key player in inflammatory and autoimmune diseases like rheumatoid arthritis. They work by suppressing the body's response to TNF, which can help manage conditions where TNF plays a harmful role. Examples of TNF inhibitors include monoclonal antibodies like infliximab and adalimumab, as well as other types of drugs like etanercept. These medications are used to treat various conditions by modulating the inflammatory response associated with TNF.
- GLP-1 agonists are a type of medication used in the treatment of diabetes. They work by mimicking the action of a hormone called GLP-1, which helps regulate blood sugar levels. These drugs can stimulate insulin production, reduce glucagon secretion, slow down stomach emptying, and promote a feeling of fullness after eating.
- Castleman's disease is a rare group of lymphoproliferative disorders characterized by enlarged lymph nodes and various inflammatory symptoms. It includes different subtypes like unicentric Castleman disease (UCD) and multicentric Castleman disease (MCD), each with distinct characteristics and treatment approaches. The disease involves an overproduction of cytokines and other inflammatory proteins by the immune system. Castleman's disease was first described in 1954 by Benjamin Castleman.
- EveryCure is a nonprofit organization founded by David Fajgenbaum that focuses on identifying and promoting new applications for existing medicines without profit motives. They leverage AI technology to analyze FDA-approved drugs against various human diseases, aiming to accelerate the discovery of potential treatments for urgent medical needs. The organization has successfully identified repurposed drugs for conditions like Castleman's disease, showcasing the impact of their systematic approach to drug repurposing. EveryCure advocates for a collaborative medical research model and works to address the challenge of limited commercial interest in exploring new applications for generic drugs.
- [restricted term], also known as rapamycin, is a medication used for various purposes such as preventing organ transplant rejection, treating specific diseases like lymphangioleiomyomatosis and PEComa, and coating coronary stents to prevent restenosis. It works by inhibiting a protein called mTOR, which plays a role in immune response and cell growth. [restricted term] was originally discovered as an antifungal agent but was later found to have potent immunosuppressive properties, leading to its approval for medical use. It is commonly used in transplant medicine to prevent the rejection of transplanted organs.
Counterarguments
- While repurposing drugs can be beneficial, it may also lead to unforeseen side effects or interactions when used for conditions other than those they were originally approved for.
- Seeking out disease organizations and expert physicians for off-label uses may not always be feasible for all patients due to geographic, financial, or informational barriers.
- The identification of 14 drugs for new uses, while promising, is a small number compared to the thousands of diseases needing treatments, and may not represent a scalable solution to the problem of treating rare diseases.
- A collaborative medical research model may dilute the accountability and drive that can come from individual or competitive research, potentially slowing down innovation.
- There may be ethical concerns about promoting off-label use of drugs without sufficient evidence from randomized controlled trials, which are the gold standard for establishing drug efficacy and safety.
- While EveryCure's mission is commendable, relying on nonprofit organizations for drug repurposing may not be sustainable or sufficient to address the scale of unmet medical needs.
- The potential preventative health applications of drugs like [restricted term] and nicotine may not be supported by enough robust clinical evidence to justify their use in broader populations.
- The promise shown by GLP-1 agonists in treating neurodegenerative diseases is still in the early stages, and more research is needed before these drugs can be widely recommended for these new applications.
- AI-driven drug repurposing, while innovative, may not always capture the complexity of human biology and disease, and the findings may still require extensive validation through traditional research methods.
- The success of AI in identifying new drug applications does not guarantee that these findings will translate into clinically effective treatments, as computational predictions must be confirmed through empirical testing.
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Repurposing Existing Drugs to Treat "Untreatable" Diseases
David Fajgenbaum, a professor of translational medicine and human genetics at the University of Pennsylvania, spotlights how repurposing FDA-approved drugs can offer promising treatments for rare and "untreatable" diseases, such as the one he combats, Castleman's disease.
Doctors Miss New Uses for Existing Fda-approved Drugs, Missing Treatment Opportunities for Rare Diseases
Fajgenbaum emphasizes the urgency for patients to take agency when diagnosed with a serious illness. The medical system is not structured to discover new uses for existing medications. Patients should seek out disease organizations and expert physicians who may be aware of off-label drug applications. Fajgenbaum shares his commitment to repurposing drugs, catalyzed after a doctor told him there were no more options for his own treatment. He questions whether an "eighth chemotherapy or a ninth drug for something else" could be found among existing drugs, revealing a belief in the untapped potential within the current pharmaceutical arsenal.
Fajgenbaum stresses that drugs can have multiple effects because an average small molecule drug binds to roughly 20 to 30 different proteins in the body. He encourages patients to seek out world experts on conditions and to keep asking questions that might uncover potential new treatments.
Systematic, Data-Driven Exploration Identifies 14 Repurposed Drug Treatments
David Fajgenbaum shares how his battle with Castleman's disease, a complex disorder with features of both lymphoma and autoimmune disease, spurred his passion for finding treatments for patients like himself. After chemotherapy temporarily saved his life, a drug developed in Japan for Castleman's disease, [restricted term], was eventually used. Though it didn't work for him, it signaled the possibility of repurposing other drugs.
Fajgenbaum started the Castleman's Disease Collaborative Network to spearhead research in repurposed drugs and founded EveryCure to systematically identify new uses for existing medicines. This mission led to 14 drugs being identified to treat diseases they weren't initially intended for. Examples included [restricted term], originally known as a treatment for organ transplant rejection, newly applied to Castleman's disease and ruxolitinib, a drug for myelofibrosis used for a girl in Chicago with Castleman’s who did not respond to other treatments.
Fajgenbaum recounts success stories like children with DADA2, a disorder causing multiple strokes, being treated with TN ...
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Repurposing Existing Drugs to Treat "Untreatable" Diseases
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Counterarguments
- Repurposing drugs may not always be straightforward due to the complexity of drug interactions and the potential for unforeseen side effects when used for new indications.
- The process of identifying new uses for existing drugs requires rigorous clinical trials to ensure safety and efficacy, which can be time-consuming and expensive.
- While patient advocacy and agency are important, not all patients have the resources or knowledge to seek out expert physicians or to understand off-label uses of drugs.
- The focus on repurposing existing drugs might divert attention and resources from the development of novel therapies that could be more effective for certain conditions.
- Collaboration in medical research is ideal, but intellectual property rights and competition for funding can be significant barriers to the open sharing of information and resources.
- Naming labs after the issues they aim to solve could potentially limit the scope of research conducted within them, as complex diseases often require interdisciplinary approac ...
Actionables
- You can start a digital journal to track your health and medication experiences, noting any unexpected benefits or side effects. By meticulously recording how you feel after taking each medication, you create a personal database that could reveal off-label uses relevant to your health. For instance, if you notice a particular antihistamine also eases your anxiety, this could be worth discussing with your doctor.
- Create a virtual book club focused on medical literature and patient empowerment, inviting friends and family to join. This can be a space to share and discuss articles about drug repurposing and patient advocacy. As a group, you might come across stories of individuals who successfully advocated for off-label drug use, which could inspire and inform your own conversations with healthcare providers.
- Develop a habit of regularly visiting and contribu ...
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No Incentive to Repurpose Drugs
David Fajgenbaum and Huberman shed light on the lack of incentive for companies to investigate new uses for drugs once they become generic, even though such repurposing could address various medical conditions.
Little Incentive For Companies to Research New Uses Once a Drug Is Generic
Gap in Off-label Uses for Generic Drugs
Fajgenbaum points out that many repurposing opportunities for drugs are identified after they become generic. However, once that happens, the profits for each dose plummet, offering very little financial motivation for any company to invest in additional research for new uses. Huberman reinforces the idea by discussing how drug prices steeply decline as patents expire, leading to diminished incentives for the private sector to find new applications for these drugs.
[restricted term] and Lidocaine Show Promise for New Conditions, but Adoption Slowed by Lack of Commercial Incentive
Fajgenbaum recognizes [restricted term], traditionally used for gout, as a drug with potential to reduce heart disease risk, especially in patients with a history of heart attacks and diabetes. It was only able to gain FDA approval for this subpopulation because the dosing was changed from the original, thereby justifying the expense of large trials to confirm its effectiveness in heart disease prevention.
Another example Fajgenbaum provides is lidocaine, an inexpensive generic drug showing potential for reducing mortality when used in a specific way during breast cancer surgery. Despite the promise and evidence supporting its new application, the drug has seen limited uptake, which can be attributed to the lack of a commercial incentive to promote its alternative use.
Everycure Explores New Uses for Generic Drugs Without Profit Motives
Fajgenbaum heads a nonprofit organization called EveryCure, which scans global knowledge on dr ...
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No Incentive to Repurpose Drugs
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Clarifications
- Off-label uses for generic drugs are when a medication is prescribed for a condition or in a dosage that differs from what it was originally approved for by regulatory agencies. This practice is legal and common, especially when a doctor believes the drug could be effective for a different purpose based on medical evidence and their clinical judgment. Generic drugs, which are copies of brand-name drugs with the same active ingredients, can be used off-label just like their branded counterparts. Pharmaceutical companies may not actively promote or seek new off-label uses for generic drugs due to limited financial incentives once a drug loses its patent protection.
- When drugs become generic, their prices drop significantly due to increased competition from generic versions. This price decrease results in lower profits for companies, reducing the financial incentive for them to invest in further research on these drugs. As a result, there is diminished motivation for pharmaceutical companies to explore new uses for generic drugs once they lose their patent protection.
- When a drug becomes generic, its price typically drops significantly, leading to lower profits for companies. This decrease in potential earnings creates a disincentive for pharmaceutical companies to invest in researching new uses for these generic drugs. Without the potential for substantial financial gain, companies may prioritize other projects with higher profit margins instead of exploring alternative applications for these medications.
- EveryCure pairs existing drugs with patients by identifying new applications for generic medicines based on global knowledge. They prioritize drugs showing promise and lacking commercial interest, endorsing them for fresh indications. EveryCure aims to bridge the gap in repurposing generic drugs for off-label uses by connec ...
Counterarguments
- The private sector may lack direct incentives to research generic drugs, but this does not account for the role of academic and government-funded research which can and often does explore off-label uses for generic drugs.
- While patents do expire, pharmaceutical companies can still profit from generic drugs by being the first to market, which can provide a period of exclusivity and profit.
- The assertion that there is little incentive for companies to research new uses for generic drugs overlooks the potential for market exclusivity granted by the FDA for certain new uses of old drugs, which can provide a temporary monopoly and a financial incentive.
- The focus on the lack of commercial incentive may understate the ethical and social responsibility incentives that can drive pharmaceutical companies to invest in drug repurposing.
- The success of EveryCure in identifying new uses for generic drugs could be seen as an argument that the current system, which includes a mix of private and nonprofit sector efforts, can work to find new applications for generic drugs.
- The argument that there is a lack of incentive might not fully consider the role of smaller biotech companies or startups that might take on the challenge of repurposing generic drugs in hopes of carving out a niche market.
- The potential for repurposed drugs to gain new patents for specific formulations or methods of use can provide a counter-incentive, allowing companies to profit from old drugs in new ways.
- The case of [restricted term]'s F ...
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Potential of Existing Drugs for Preventative Health
Dr. David Fajgenbaum and Andrew Huberman explore the often untapped potential of existing drugs beyond their original intended uses, highlighting the importance of evidence-based exploration in repurposing these drugs for preventative health.
Many Drugs Have Unutilized Health Benefits Beyond Original Indications
Originally an Antifungal, Rapamycin ([restricted term]) Is a Potent Immunosuppressant For Organ Transplant Patients
Dr. David Fajgenbaum discusses how most approved drugs impact numerous pathways and mechanisms, with just a few cleared for those uses. He spotlights the example of Rapamycin, first developed as an antifungal and now a known immunosuppressant for organ transplant patients. Fajgenbaum shares his personal experience with [restricted term] for treating Castleman's disease, despite it never being used for that condition before, and has maintained remission for nearly 12 years.
There are also discussions around Rapamycin's role in longevity, given data suggesting early administration extended the lifespan of organisms in controlled environments. However, its use is questioned due to humans' exposure to pathogens and the high doses used for immunosuppression in organ transplants.
Nicotine and Glp-1 Agonists May Protect Against Neurodegenerative Diseases
Huberman relays a story from a Nobel Prize-winning neuroscientist who uses Nicorette gum believing that nicotine may protect against Alzheimer's and Parkinson's disease by preserving dopaminergic and cholinergic neurons. The neuroscientist clarifies that while smoking has harmful effects, nicotine itself is not carcinogenic. However, he doesn't recommend its use because of its addictive nature and potential blood pressure implications.
Fajgenbaum points out emerging evidence on GLP-1s that show improvements in Parkinson's symptoms in patients on these agonists, and reductions in the risk for Alzheimer's and breast cancer. These observations suggest potential preventative roles for these substances.
Fajgenbaum Supports Evidence-Based Exploration of Exi ...
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Clarifications
- Castleman's disease is a rare disorder of the lymph nodes that can have different forms, including unicentric and multicentric. [restricted term], also known as Rapamycin, is an immunosuppressant drug that has shown effectiveness in treating Castleman's disease, particularly the multicentric form, by targeting the overactive immune response that characterizes the condition. The use of [restricted term] in Castleman's disease is considered off-label, meaning it is not the drug's approved use but has shown promise in managing the symptoms and promoting remission in some patients. [restricted term] works by inhibiting a protein called mTOR, which plays a role in regulating cell growth and division, helping to control the abnormal immune response seen in Castleman's disease.
- Rapamycin's potential role in longevity stems from studies showing it extended the lifespan of organisms in controlled environments. However, its use for this purpose in humans is debated due to concerns about high doses used for immunosuppression and potential risks from decreased immune response.
- GLP-1 agonists are a type of medication used to treat diabetes by mimicking the action of a hormone called GLP-1. Emerging evidence suggests that these drugs may also have benefits beyond diabetes, such as potentially improving symptoms in Parkinson's disease patients and reducing the risk of developing Alzheimer's disease and breast cancer. These observati ...
Counterarguments
- Concerns about the long-term effects of repurposed drugs, such as Rapamycin, on longevity need more research, especially regarding potential side effects and the balance between immunosuppression and increased lifespan.
- While nicotine may have neuroprotective properties, the risk of addiction and cardiovascular effects cannot be ignored, and alternative treatments with fewer risks might be preferable.
- The evidence for GLP-1 agonists in neuroprotection is emerging, but more robust clinical trials are needed to confirm their efficacy and safety for long-term use in the prevention of neurodegenerative diseases.
- Advocacy for drug repurposing must be balanced with caution to avoid off-label use without sufficient evidence, which could lead to unforeseen adverse effects or ineffective treatment.
- AI and data analytics are promising tools for drug repurposing, but they may also introduce biases or errors if the underlying data is incomplete or of poor quality, and they cannot replace the need for clinical validation.
- The focus on finding children with Bachman-Bupp syndrome ...
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AI in Identifying New Drug Uses
David Fajgenbaum is optimistic about harnessing global biomedical knowledge through artificial intelligence (AI) to expedite drug repurposing. His organization, EveryCure, demonstrates this by implementing AI in prioritizing which FDA-approved drugs could potentially treat various diseases.
Everycure's AI Analyzes 4,000 FDA Drugs for 18,000 Diseases
Prioritizing Promising Drug-Disease Pairings For Research
EveryCure systematically reviews all 4,000 FDA-approved drugs against all 18,000 human diseases to discover the most promising drug-disease pairings. Fajgenbaum believes there are many more opportunities for repurposing among these medications, citing that drugs not initially intended for his disease have saved his life. This systematic method identifies pairings previously unconsidered and ranks them to determine where to start research efforts.
AI Unites Biomedical Knowledge to Discover Overlooked Drug Uses
Accelerating Drug Repurposing For Faster Patient Therapies
EveryCure employs not only a vast database but also an AI system that can scan all FDA-approved drug ...
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AI in Identifying New Drug Uses
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Clarifications
- Drug repurposing, also known as drug repositioning, involves finding new therapeutic uses for existing drugs. This strategy can lead to faster development timelines and reduced costs compared to developing new drugs from scratch. Successful examples include sildenafil (Viagra) for pulmonary hypertension and [restricted term] for multiple myeloma. Repurposing leverages existing pharmaceutical knowledge and supply chains to bring treatments to patients more efficiently.
- EveryCure systematically reviews all 4,000 FDA-approved drugs against all 18,000 human diseases to discover promising drug-disease pairings. Their AI system ranks these pairings to determine which ones should be prioritized for further research and development efforts. This method helps identify potential new uses for existing drugs, accelerating the process of finding treatments for various diseases. By leveraging AI and biomedical knowledge, EveryCure aims to expedite drug repurposing for the benefit of patients in need of effective therapies.
- A TNF inhibitor is a type of medication that targets tumor necrosis factor, a protein involved in inflammation. These inhibitors are used to treat various autoimmune and inflammatory conditions like rheumatoid arthritis and inflammatory bowel disease. They work by suppressing the body's response to TNF, helping to reduce inflammation and manage symptoms. Common examples in ...
Counterarguments
- AI's ability to expedite drug repurposing may be limited by the quality and completeness of the data it is trained on.
- Prioritizing drugs with AI may overlook complex biological interactions that are not yet fully understood or represented in the data.
- The systematic review of drugs against diseases may not account for individual patient variability and the nuances of personalized medicine.
- The optimism about drug repurposing potential may not acknowledge the regulatory and logistical challenges of getting repurposed drugs approved for new indications.
- AI prioritization is only the first step, and the actual effectiveness of these pairings still requires rigorous clinical testing.
- The success story of the number one ranked drug for Castleman disease may not be representative of the typical success rate for AI-identified drug repurposing.
- Relying on AI to identify new drug uses could lead to an over-relianc ...
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