Using Existing Drugs in New Ways to Treat & Cure Diseases of Brain & Body | Dr. David Fajgenbaum
Dr. David Fajgenbaum, MD, professor at UPenn, discusses how many approved drugs can treat other diseases, often unknown to doctors. He shares his story of curing his Castleman's disease using repurposed drugs, emphasizing self-agency, mindset, and the Every Cure initiative to find novel treatments for all.
Deep Dive Analysis
15 Topic Outline
Empowering Patients: New Uses for Existing Medicines
Drug Repurposing: Incentives, Patents, and Examples
Finding Reliable Health Information and Disease Organizations
Need for Integrated Medical Databases and Connections
Every Cure's Approach: Repurposing Examples and Database
David's Personal Journey: Glioblastoma, Castleman Disease
Stress, Immune System, and Autoimmune Disease
Castleman Disease Treatment and Chemotherapy
Physician Education and the 'Santa Claus Theory'
Personal Discovery of Rapamycin Treatment
Athletic Background and Resilience in Illness
Leveraging AI for Drug Repurposing
Repurposing for POEMS Syndrome and Risk Mitigation
Preventive Health, Bioprospecting, and AI's Role
Parenting Healthcare and the Hope-Action-Impact Circuit
6 Key Concepts
Drug Repurposing
The process of finding new uses for existing, approved medications to treat diseases other than their originally intended purpose. Many drugs impact multiple biological pathways, making them potentially useful for a wider range of conditions, but the current system often doesn't incentivize discovering these new applications.
Santa Claus Theory of Civilization
An initial belief that scientists and doctors are constantly collaborating in a systematic, efficient manner to quickly find and deliver treatments. This theory often gives way to the realization that biomedical research and healthcare progress can be piecemeal, random, and not always as swift or coordinated as one might hope.
Castleman Disease
A rare and deadly atypical lymphoproliferative disorder that shares features with both lymphoma and autoimmune diseases. In this condition, the immune system becomes highly activated, producing excessive cytokines that attack and cause the shutdown of vital organs throughout the body.
Biomedical Knowledge Graphs
A sophisticated mapping system that organizes and connects all known information about human biology, including drugs, diseases, genes, and pathways. These graphs, often powered by AI, are used to quantify the likelihood of every drug treating every disease, helping to identify promising repurposing opportunities.
Hope, Action, Impact Circuit
A psychological and potentially neurological feedback loop where an initial sense of hope for a future outcome drives a person to take action. This action then leads to an impact, which in turn reinforces and generates more hope, perpetuating a cycle of engagement, perseverance, and resilience.
Bioprospecting
The process by which pharmaceutical companies and researchers explore natural sources, such as plants, fungi, or soil samples, to discover new compounds or molecules that can be developed into drugs or treatments for various conditions.
7 Questions Answered
Yes, many approved medications impact at least 20-30 different pathways in the body and can successfully treat or even cure diseases other than the ones they are typically used for, but the medical system is not well-structured to discover or promote these new applications.
Patients should connect with disease-specific advocacy groups, seek out world experts for their condition, and actively ask questions to their physicians about alternative or repurposed treatments, even if initially told there are no other options.
Castleman disease is a rare and severe atypical lymphoproliferative disorder where the immune system becomes overactive, producing inflammatory cytokines that cause vital organs to shut down, leading to multi-organ failure.
Once a drug becomes generic, its profitability significantly decreases, removing the financial incentive for pharmaceutical companies to invest in expensive research and development to find and prove new applications for these medicines.
While not definitively proven to cause autoimmune diseases, stress and lack of sleep are strongly associated with exacerbating flares in individuals who already have autoimmune conditions, potentially due to their impact on immune system balance and cytokine production.
AI platforms and machine learning models can analyze vast biomedical knowledge graphs to quantify the likelihood of every drug treating every disease, helping researchers prioritize and identify the most promising connections for further investigation and clinical trials.
The 'Hope, Action, Impact' circuit describes a self-reinforcing cycle where hope for a future outcome drives an individual to take action, which then leads to a positive impact, further strengthening their hope and motivating continued action.
21 Actionable Insights
1. Cultivate Hope-Action-Impact Circuit
To overcome challenges, foster a ‘hope, action, impact’ circuit: envision a hopeful future, take action, observe the impact, which then reinforces hope and drives further action. This provides sustained motivation and resilience, helping navigate difficult periods by focusing on incremental progress.
2. Actively Search Repurposed Drugs
When facing a disease, actively search for existing drugs approved for other conditions that might treat your specific ailment. Many approved drugs impact multiple biological pathways, and the current system often overlooks these alternative uses, necessitating personal advocacy.
3. Consult Disease Advocacy Groups
Connect with disease-specific advocacy groups for your condition, as they are often well-connected with global physicians and may have information about treatments or drugs being used elsewhere that your local doctor might not know.
4. Identify World’s Leading Experts
Seek out and consult with the world’s leading experts for your specific medical condition, as they often possess unique insights into novel or less-known treatments and can provide valuable guidance beyond standard protocols.
5. Question Doctor for Alternatives
After receiving a treatment recommendation, actively question your doctor about alternative or additional treatment options, including drugs repurposed from other conditions. This encourages a comprehensive exploration of possibilities and ensures you are aware of all potential avenues.
6. Endure in Short Increments
When experiencing overwhelming, prolonged pain or suffering, focus on enduring for very short, manageable periods (e.g., one minute, one hour, one day) rather than the entire duration. This strategy makes seemingly insurmountable challenges feel more achievable and helps maintain the will to continue.
7. Leverage Social Support
During times of severe illness or challenge, lean on the social support of family and loved ones, as their strength and presence can provide crucial emotional and psychological support to help you persevere. Feeling their strength can literally help you keep going.
8. Lidocaine for Breast Cancer Surgery
For localized breast cancer, discuss with your surgeon the injection of lidocaine around the tumor 8-10 minutes before surgery. A large trial showed a 29% reduction in five-year mortality for women who received this inexpensive treatment.
9. Sirolimus for Castleman Disease
For Castleman disease, especially if other treatments fail, discuss with your doctor the possibility of using Sirolimus (Rapamycin), an mTOR inhibitor approved for organ transplant rejection. This drug has shown to induce long-term remission in patients with the disease.
10. PD-1 Inhibitor for Angiosarcoma
For metastatic angiosarcoma, discuss with your doctor the potential use of a PD-1 inhibitor (like Pembrolizumab), particularly if PD-L1 expression is high in the tumor. This drug, initially for melanoma/lung cancer, has shown transformative results in some angiosarcoma patients.
11. Colchicine for Heart Attack Risk
If you have had a prior heart attack, especially with diabetes, discuss with your doctor the use of colchicine (at a slightly different dose than for gout treatment) to reduce heart disease risk. This drug has shown a substantial reduction in heart disease risk in this population.
12. DFMO for Bachman-Bopp Syndrome
For children diagnosed with Bachman-Bopp syndrome, explore the use of DFMO (a drug for African sleeping sickness) as early as possible. DFMO binds to and inhibits the overactive OCE1 enzyme, which can reverse severe symptoms and improve quality of life.
13. Ruxolitinib for Castleman Disease
For Castleman disease, particularly if unresponsive to other treatments, discuss with your doctor the potential use of Ruxolitinib, a drug typically used for myelofibrosis. This drug has been successfully repurposed to treat Castleman disease patients.
14. TNF Inhibitor for Castleman Disease
For Castleman disease, discuss with your doctor the potential use of a TNF inhibitor (like Adalimumab). AI-identified and lab-supported evidence suggests this drug, initially for other inflammatory conditions, can induce remission in Castleman disease patients.
15. Myeloma Drugs for Poem Syndrome
For Poem Syndrome, especially in severe, life-threatening cases, discuss with your doctor the use of drugs typically prescribed for multiple myeloma. Myeloma and Poem Syndrome share similar mechanisms, and these drugs have shown to induce remission in Poem Syndrome patients.
16. Proactively Seek Health-Extending Drugs
Even if healthy, proactively seek information about existing prescription or over-the-counter medications and molecules that could potentially extend your life or offset disease risk. This allows for informed decisions about potential prophylactic treatments, filling gaps in readily available health information.
17. Aspirin for Colon Cancer Recurrence
Consider discussing with your doctor the use of aspirin to reduce the risk of colon cancer recurrence, especially if you have a mutation in the mTOR pathway. Aspirin has been shown to reduce recurrence risk, but is underutilized for this purpose.
18. Understand Multi-Pathway Drug Effects
Recognize that most approved drugs impact multiple biological pathways and mechanisms across the human brain and body, often far beyond their primary intended use. This understanding highlights the vast potential for drug repurposing.
19. Contribute to EveryCure Research
Contribute to drug repurposing efforts by submitting ideas for off-label drug uses or volunteering your medical/scientific expertise at everycure.org/ideas or everycure.org/experts. This helps EveryCure identify potential new uses for existing drugs and gather expert guidance.
20. Spread EveryCure Awareness
Help raise awareness about the potential of drug repurposing and the work of EveryCure by following them on social media (at everycure.org and beyond) and sharing their content, such as their TED Talk. Increased awareness can help more patients and doctors discover existing treatments.
21. Donate to EveryCure
Support the non-profit EveryCure financially by donating at everycure.org/donate to help fund clinical trials and research into drug repurposing. Financial contributions enable the organization to conduct the necessary work to prove and disseminate new uses for existing medicines.
6 Key Quotes
I'm going to dedicate the rest of my life, however long that's going to be... to trying to find out, is there a drug out there that could help me and other patients with my disease that's made for another condition?
David Fajgenbaum
No one should suffer if there's a drug at your CVS that could help you.
David Fajgenbaum
It's one thing if you have a horrible disease and everyone dies from it and there's nothing out there. But I think it's so much more heartbreaking when you think that, oh my gosh, there was something there. We as a system hadn't done the work to make sure people get the medicine.
David Fajgenbaum
We call a drug, you know, we say it does one thing, but actually it's doing a lot of other things in the body.
David Fajgenbaum
The answers may already be here.
Andrew Huberman
You can do anything for like one minute or one hour or one day, but you can't do, like I, if you told me at the beginning, David, you're going to be in the worst pain of your life for six months, it's going to be horrible. You're going to suffer. Your organs will be failing. No way I would have the strength to survive that, but I could survive for one minute and one hour and one day.
David Fajgenbaum
1 Protocols
Navigating a Health Journey for New Treatment Options
David Fajgenbaum- Connect with the disease organization or advocacy group specific to your condition to gather information and connect with physicians.
- Identify and seek consultation with the world's leading expert(s) for your specific medical condition.
- Actively ask questions to your physicians, even if told there are no more options, inquiring about other potential treatments or drugs being used elsewhere in the world.