Peter Hiesinger, associate professor at the University of Texas Southwestern Medical Center in Dallas, was awarded an MDA research grant totaling $300,000 over a period of three years to investigate the causes of type 2B Charcot-Marie-Tooth disease (CMT2B).
CMT2B is caused by mutations in a gene called rab7. The protein made from the gene performs a critical function in the degradation of debris in all cells. “Even though the gene is known, it is unclear how the mutations found in patients affect the gene’s function,” Hiesinger says. Without knowing how the mutation causes disease, it is difficult to design a therapy to treat it. He has developed models of the disease that suggest the mutation causes the protein to no longer be active, and that this loss of function affects nerve cells before other cells in the body.
“Our findings explain the genetic dominance [only one mutant copy of the gene, from either parent, is needed to develop the disease] and reveal a particular sensitivity of nerve cells for a defect in debris removal,” says Hiesinger. “This discovery opens the door for an understanding and a potential therapy of CMT2B based on the molecular manipulation of the underlying cause.
“Importantly,” he adds, “we suggest an increase of rab7 function as a therapeutic opportunity, in contrast to the currently suggested reduction of mutant gene function.”
In this project, Hiesinger will test this hypothesis of disease in a fly model of CMT2B and investigate rab7 function in detail.
Funding for this MDA grant began August 1, 2013.