The major risk factor for both cancer and Alzheimer's disease is aging. Changes in our biology that happen as we age contribute to the development of both diseases. Better understanding the biology of aging will help us develop drugs to treat Alzheimer's. It will also help us identify drugs currently used to treat cancer that could also be "repurposed" to treat Alzheimer's patients.
Large population studies have shown that people who get cancer are less likely to get Alzheimer's disease, and vice versa. But researchers don't yet know why this happens. Does cancer or the drugs used to treat it offer protection against Alzheimer's? Or do cancer patients have shorter life spans and thus a lower likelihood of living to the age when Alzheimer's generally develops?
The Alzheimer's Drug Discovery Foundation (ADDF), where I serve as Executive Director, is investing in studies to test cancer medications for Alzheimer's patients. We know that while the two diseases share some underlying biological processes, the goals of treatment differ. So drugs used to treat cancer may be used--albeit in different ways--for Alzheimer's patients.
Among the most promising types of cancer drugs being tested for Alzheimer's are tyrosine kinase inhibitors. These drugs block the action of factors involved in cancer cell signaling, growth, and division. They have been found effective in treating some forms of cancer by keeping cancer cells from growing. Nilotinib (Tasigna™), an FDA-approved tyrosine kinase inhibitor used to treat leukemia, is thought to promote the removal of Alzheimer's-associated proteins, such as beta-amyloid and tau. Activating this removal process prevents the formation of toxic plaques and tangles that lead to the death of neurons and the development of Alzheimer's. In preclinical studies, Raymond Scott Turner, MD, PhD, and colleagues at Georgetown University found that nilotinib reverses cognitive impairment and reduces toxic protein buildup in animal models of Alzheimer's.
Another area researchers are pursuing involves epigenetic-targeted drugs. Epigenetic processes can turn genes on and off and increase or decrease how much they are expressed. Therefore, an epigenetic drug that influences genes involved in learning and memory might help Alzheimer's patients. Epigenetic treatments were first created for cancer, but researchers are now using that technology for Alzheimer's. Tamara Maes, PhD, at Oryzon Genomics in Spain developed an epigenetic treatment for cancer that is in clinical trials. In 2010, with funding from the ADDF, they took the knowledge they gained and began developing ORY-2001, the first epigenetic treatment for Alzheimer's. After successful preclinical testing, that drug entered a Phase 1 clinical trial in April. Berkley Lynch, PhD, and the team at Massachusetts-based Rodin Therapeutics are developing a different epigenetic treatment for Alzheimer's disease to "turn down" genes that affect our brains' synapses and impair learning and memory.
The folding of proteins into their proper three dimensional configurations is essential for normal function; however, stabilizing the conformations of disease-causing proteins can have detrimental consequences. Molecular chaperones aid in proper protein folding and maintain protein stabilization. One of these molecular chaperones, Hsp90, stabilizes many of the proteins that drive tumor growth. Several drugs that inhibit Hsp90 are now being tested in clinical trials for cancer to halt this action in tumor cells. In nerve cells of Alzheimer's patients, Hsp90 becomes overactive, a process that is thought to stabilize toxic forms of tau leading to the formation of tangles that kill neurons. With ADDF funding, researchers at Yuma Therapeutics are developing a drug to inhibit Hsp90 and reduce levels of toxic tau proteins in neurons. Yuma is now doing preclinical testing on its drug.
Many other areas of cancer drug repurposing are being explored by researchers at universities and biopharmaceutical companies worldwide. The ADDF is on the forefront of efforts to advance these programs. We have convened two think tanks to encourage leading neuroscience and oncology researchers to share knowledge and consider new opportunities for drug development. And the ADDF continues to find and fund the most promising drug repurposing programs. To prevent and treat Alzheimer's disease, we have to learn from the successes in other fields and continue to test promising ideas.