Grantee Carmela Abraham, PhD, a professor at Boston University School of Medicine, is developing a new class of drugs to combat Alzheimer’s disease. Dr. Abraham discovered that levels of Klotho, a large protein produced in the kidney and brain, are low in aging brains and in patients with Alzheimer’s disease and multiple sclerosis. Humans and animals with higher levels of Klotho demonstrate better cognitive abilities. Studies have also shown that mice with higher levels of Klotho live up to 30 percent longer than normal mice and have better memory.
With five years of support from the Alzheimer’s Drug Discovery Foundation (ADDF), Dr. Abraham was able to develop small molecule compounds that boost the amount of Klotho protein in the brain. Within the central nervous system, Klotho appears to protect neurons from the damage and degeneration that lead to Alzheimer’s disease. While most treatments in development for Alzheimer’s try to remove amyloid plaques from the brain, Dr. Abraham’s takes a different approach. By increasing Klotho, she aims to protect neurons from the damage caused not only by amyloid plaques but also misfolded tau proteins and inflammation. Her latest grant from the ADDF, awarded in 2015, supports preclinical testing of the most promising of the Klotho-enhancing compounds.
Now, Dr. Abraham and the team at Klogene plan to develop their most promising compounds into oral drugs, which can then be tested in human clinical trials.