A team of researchers at the Thomas J. Long School of Pharmacy and Health Sciences has discovered a potential drug to prevent an inherited rare form of heart failure which affects nearly 4% of African Americans. This therapy could provide first potential drug therapy for Familial amyloid cardiomyopathy (FAC), for which the only currently available cure is a combination of heart and liver transplant.

Transthyretin (TTR) is a protein that is synthesized by the liver and secreted into the blood, where it acts as the primary carrier of vitamin A. A number of genetic mutations decrease the stability TTR causing (FAC), the abnormal deposition of insoluble proteins called amyloid in the heart tissue. The TTR mutations causing (FAC) occur when the protein mutation causes the protein to unravel, as a result allowing the protein to aggregate. The aggregation of the proteins attacks the normal tissues of the heart thus causing heart failure.

RS37226_Mamoun Lab7AG10, is a small molecule drug that effectively stabilized mutant TTR when tested in serum samples obtained from patients with FAC. Discovered by Mamoun M. Alhamadsheh, B.Pharm., Ph.D. and his team, which included University of the Pacific graduate students Sravan C. Penchala ’15, Yu Wang ’13 and faculty Dr. Miki S. Park and Dr. William K. Chan, researchers at the Scripps Research Institute and Dr. Isabella Graef at Stanford School of Medicine, they also found AG10 to be orally available and nontoxic in animals, making it attractive for pre-clinical evaluation.

Currently, there are no Food and Drug Administration (FDA)-approved drugs available for treatment of these diseases. Tafamidis, which was rejected by the FDA due to the lack of efficacy, is the only drug in clinical trials for a similar disease called familial amyloid polyneuropathy.

“This discovery will be critical in furthering the potential for better treatment of cardiac patients. Cardiac health conditions are one of the leading causes of death in adults in the U.S. I’m hopeful that Dr. Alhamadsheh and his team’s research efforts will result in improved patient outcomes,” said Dean Phillip Oppenheimer.

To learn more about Dr. Alhamadsheh, visit his faculty profile.

The research was published in the Proceedings of the National Academy of Sciences of the United States of America in June.

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