Empowered Patient Podcast Using TKIs to Remove Toxic Proteins in the Brain with Chris Hoyt KeifeRx
Chris Hoyt, CEO of KeifeRx, talks about the oral medication being developed that uses tyrosine kinase inhibitors (TKIs) and autophagy to remove unwanted proteins. Research done by Georgetown University on leukemia, led by Dr. Charbel Moussa, found that lower doses of drugs like nilotinib and bosutinib could cross the blood-brain barrier and remove toxic proteins on an intracellular basis. This research has been used to develop treatments for neurodegenerative conditions with promising results in reducing cognitive decline.
Chris explains, "Essentially, the way TKIs work in the body, and particularly in the case of the neurodegenerative conditions that we're using them to treat at KeifeRx, is they trigger a mechanism called autophagy, which essentially is the cell's garbage disposal mechanism. What we're doing with TKIs is using that mechanism to remove toxic proteins. TKIs have mostly been used historically in cancer, and particularly in leukemia. The classic use would be in cancer to try to remove as much of the tumors as you can in leukemia. In that environment, use a fairly high dose of TKIs to trigger that effect. What KeifeRx has done through work at Georgetown University is find ways to utilize that same mechanism of action in the brain."
"So over the course of a few years of initial work, we came to the conclusion that these drugs, in the case of specifically nilotinib and bosutinib, which are the two drugs where we have the use patent in neurodegeneration, that at much lower doses than what you see in cancer, these drugs can cross the blood-brain barrier and look to remove toxic proteins on an intracellular basis. So, it was a classic hunch, for lack of a better term, that Dr. Moussa had that he then carried out rigorous work over three years to first prove in animal models and then eventually through a series of small phase I and phase II trials at Georgetown."
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