Rare Disease Gene Identified; May Lead to Progress on Devasting Genetic Disease and Also Cancer

The discovery of a gene mutation that causes a rare premature aging disease could lead to the development of drugs that block the rapid, unstoppable cell division that makes cancer so deadly. Scientists at the University of Michigan (U-M) and the U-M Health System recently discovered a protein mutation that causes the devastating Hoyeraal-Hreidarsson syndrome, a specific form of dyskeratosis congenital (DC), in which precious hematopoietic stem cells can't regenerate and make new blood. People with DC age prematurely and are prone to cancer and bone marrow failure. But the study findings reach far beyond the roughly one in 1 million known DC patients, and could ultimately lead to developing new drugs that prevent cancer from spreading, said Dr. Jayakrishnan Nandakumar, assistant professor in the U-M Department of Molecular, Cellular, and Developmental Biology. The DC-causing mutation occurs in a protein called TPP1 (image). The mutation inhibits TPP1's ability to bind the enzyme telomerase to the ends of chromosomes, which ultimately results in reduced hematopoietic stem cell division. While telomerase is underproduced in DC patients, the opposite is true for cells in cancer patients. "Telomerase overproduction in cancer cells helps them divide uncontrollably, which is a hallmark of all cancers," Dr. Nandakumar said. "Inhibiting telomerase will be an effective way to kill cancer cells." The findings could lead to the development of gene therapies to repair the mutation and start cell division in DC patients, or drugs to inhibit telomerase and cell division in cancer patients. Both would amount to huge treatment breakthroughs for DC and cancer patients, Dr. Nandakumar said.
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