Scientists identify factors contributing to dwarfism

Published: December 21, 2018 by Rob Cahill

New research from The University of Texas Health Science Center at Houston (UTHealth) could open up novel ways to treat a severe inherited dwarfing condition called pseudoachondroplasia (PSACH). Findings appeared in the American Journal of Pathology.

PSACH is characterized by disproportionate short stature, joint laxity, pain, and early onset osteoarthritis. The research team identified molecular mechanisms that disrupt bone growth in people with pseudoachondroplasia. In a mouse model of dwarfism, the investigators dampened the malfunctioning mechanisms by administering either aspirin or a dietary supplement called resveratrol.

As for the next step, the group will begin a clinical trial for resveratrol in coming months to address the severe joint pain.

“This is the first study to define cellular mechanisms that preserve cellular viability at the same time preventing clearance of misfolded proteins. These results identify new therapeutic targets for this pathologic process in a wide spectrum of misfolded protein disorders such as Type 2 diabetes, Alzheimer’s disease, and tuberous sclerosis,” explained Karen L. Posey, PhD, first author and associate professor of pediatrics at McGovern Medical School at UTHealth

In 1995, a team led by McGovern Medical School professor Jacqueline T. Hecht, PhD, identified COMP as the gene that causes PSACH. In particular, COMP mutations cause misfolding of the protein. Misfolded proteins are proteins that do not have the correct 3D shape and are toxic to the cell.

Posey’s UTHealth coauthors include senior author Hecht; Francoise Coustry, PhD; Alka Veerisetty; and Mohammad Golber Hossain, PhD.

The study, titled “Novel mTORC1 mechanism suggests therapeutic targets for COMPopathies,” was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number RO1-AR057117-05 and the Leah Lewis Family Foundation. 

Hecht has appointments at two UTHealth schools. At McGovern Medical School, Hecht is vice chair for research in the Department of Pediatrics, where she holds the Leah L. Lewis Distinguished Chair, and serves as division head of the Pediatric Research Center. At UTHealth School of Dentistry, Hecht is associate dean for research, director of the Center for Craniofacial Research, and distinguished teaching professor in the Department of Oral and Maxillofacial Surgery.

-Based on a news release from the American Journal of Pathology