Sirolimus, Aging, and RUNX1-FPD: What We Can Learn from Anti-Aging Research
By Dr. Katrin Ericson
Key Points
Sirolimus (rapamycin) and aging: Originally used in organ transplants and cancer treatment, sirolimus is now being studied for its ability to slow aging and enhance immune function by targeting the mTOR pathway.
Why it matters for RUNX1-FPD: Aging and cancer are closely linked. Sirolimus may help reduce inflammation, boost immune function, and lower leukemia risk in people with RUNX1-FPD.
Ongoing clinical trial: RRP is currently sponsoring a pilot clinical trial testing a low dose of sirolimus in RUNX1-FPD patients.
At the RUNX1 Research Program, we are dedicated to finding ways to prevent blood cancer in individuals with RUNX1-FPD.
One promising avenue we are exploring is sirolimus (also known as rapamycin), a drug long used in organ transplantation and cancer treatment. Interestingly, sirolimus was discovered in a bacterium in the soil on Easter Island (Rapa Nui) over 50 years ago. Today sirolimus is gaining attention in the field of aging research.
What if there was a way to slow down aging and delay the onset of age-related diseases like cancer, heart disease, and immune dysfunction?
Scientists studying the biology of aging believe that sirolimus may hold the key to extending healthspan, the number of years we live in good health, alongside lifespan itself.
The Science Behind Sirolimus and Aging
Cancer is the leading cause of death in aging laboratory mice, and sirolimus has been shown to extend these animals lifespan, suggesting it may help delay cancer onset. Sirolimus does this by targeting a central cellular pathway called mTOR (mechanistic Target of Rapamycin), which plays a major role in how cells grow, respond to stress, and regulate energy.
Dr. Matt Kaeberlein, a researcher at the University of Washington, has been studying how aging happens and how we might slow it down. He is one of the lead scientists of a large, national study testing sirolimus in older dogs, called the Dog Aging Project.
The study has enrolled over 50,000 dogs and is designed to test whether sirolimus can extend the lives of companion dogs. A previous, smaller study in older dogs showed that sirolimus treatment resulted in remarkable benefits in improving heart function.
A recent study looked at healthy older adults taking low doses of everolimus, a medicine that works like sirolimus by targeting mTOR, and found that they had better immune function compared to those who didn't take it.
As we age, our immune system gets weaker and doesn’t respond as well to things like viruses and bacteria, but it also becomes more likely to attack the body’s own tissues, leading to autoimmune issues.
One consistent feature of aging is this rise in autoimmune activity, and research shows that sirolimus can help reduce this kind of inflammation. These findings match what has been seen in mice and suggest that sirolimus and other mTOR inhibitors could help prevent or slow down age-related diseases.
What This Means for RUNX1-FPD
We are particularly excited about this research because aging and cancer are deeply connected. As we age, our bodies accumulate genetic mutations, and our immune systems become less effective at detecting and eliminating pre-cancerous cells.
In individuals with RUNX1-FPD, this process is even more concerning, as the inherited RUNX1 mutation makes blood cells more vulnerable to transformation into pre-cancerous cells (clonal hematopoiesis) and leukemia. Additionally, Dr. Anupriya Agarwal and colleagues recently discovered that blood stem cells in RUNX1-FPD have markedly elevated levels of mTORC1.
Therefore, it makes sense to think that sirolimus might help delay or even prevent blood cancers in people with RUNX1-FPD by:
Helping the immune system spot and clear out pre-cancerous cells before they become a bigger problem
Reducing inflammation, which is known to contribute to the development of pre-cancerous cells (clonal hematopoiesis) and the progression of blood cancers
Decreasing cellular stress, which could lower the long-term effects of DNA damage
We also know that sirolimus has been successful in treating autoimmune diseases, and research from the natural history study has shown that autoimmune diseases are more common in people with RUNX1-FPD than in the general population.
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Why This Matters for Our Community
To explore these possibilities, RRP is sponsoring a pilot clinical trial testing a low dose of sirolimus (2mg/day for 6 months) in RUNX1-FPD patients. The goal of this study is to assess tolerability and collect data on potential efficacy endpoints that could support a larger Phase 2 trial.
This study has been open for six months, and while early data is promising, we need more information to fully understand whether sirolimus can play a role in preventing blood cancer in RUNX1-FPD.
By participating, patients can contribute to groundbreaking research that could help inform future studies and potential new treatment strategies.
Want to learn more or see if you qualify for the study? Contact us today. Every step we take brings us closer to a future where RUNX1-FPD patients can live longer, healthier lives without the looming risk of blood cancer.
