Researchers have identified a signaling pathway that switches on scleroderma, a rare and sometimes fatal disease that causes skin and other tissue to thicken. There is currently no cure for the condition.
The team also says they have found the chemical compounds that can turn the switch off.
“Our findings provide a new approach to developing better treatment options where few have existed,” says Richard Neubig, chairperson of the department of pharmacology and toxicology in the College of Osteopathic Medicine at Michigan State.
“There are two kinds of scleroderma, localized and systemic, with the latter often proving to be life threatening,” Neubig says. “This research shows that by inhibiting this main signaling pathway, we can block fibrosis—the thickening of tissue that occurs with the disease.”
Localized scleroderma affects the skin and causes a loss of flexibility. Systemic sclerosis can spread throughout the body, hardening organs such as the lungs, heart, gut, and kidneys.
Scleroderma is an autoimmune disorder. It’s estimated 300,000 Americans suffer from the disease with about one-third of those having the systemic form. Localized scleroderma patients usually live normal lifespans. Yet about half of systemic patients, especially with widespread skin involvement and internal organ fibrosis, will see their lives cut short.
Scleroderma’s many pathways
“The majority of drug treatments that exist today for fibrosis basically look at reducing just the inflammation,” says Dinesh Khanna, associate professor of internal medicine at the University of Michigan. “There are other drugs that block one or two of the signaling pathways that cause the disease, but scleroderma has many of these pathways.”
Published in the Journal of Pharmacology and Experimental Therapeutics, the new research could significantly change the quality of life for scleroderma patients and greatly increase the lifespan of systemic patients, Neubig says.
“Our research shows promise for the development of a new drug that can reverse the fibrosis process by flipping the main switch on all of the signaling pathways. By validating this core switch as a viable drug target, we can now continue our work to improve the chemical compounds so they will work with doses that are appropriate for people. It’s definitely promising.”
A donation from Jon and Lisa Rye, a Michigan family who has experienced the effects of scleroderma, and the family’s crowdfunding site, the Scleroderma Cure Fund, helped support the research.
Source: Michigan State