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U-M, MSU researchers find "off" switch for scleroderma

U-M, MSU discovery brings researchers one step closer to unraveling devastating disease

An original version of this article was published by Michigan State University

ANN ARBOR, Mich. — U-M researchers are in the news for their role in identifying a signaling pathway that switches on scleroderma, a rare and sometimes fatal disease that causes skin and other tissue to thicken and has no cure.

The findings also identify chemical compounds that can turn the switch off, according to the research that appears in The Journal of Pharmacology and Experimental Therapeutics.” 

“The majority of drug treatments that exist today for fibrosis basically look at reducing just the inflammation,” says Dinesh Khanna, M.D., M.S., the Marvin and Betty Danto Research Professor of Internal Medicine at the U-M Medical School and director of the U-M Scleroderma Program.

“There are other drugs that block one or two of the signaling pathways that cause the disease, but scleroderma has many of these pathways.”

The work originated in the lab of former U-M pharmacology professor Richard Neubig, M.D., Ph.D., who is now chairperson of the Department of Pharmacology and Toxicology in MSU’s College of Osteopathic Medicine. 

Medicinal chemistry support for the project is being provided by the Vahlteich Medicinal Chemistry Core, directed by Scott Larsen, Ph.D., Research Professor of Medicinal Chemistry in the College of Pharmacy. 

Larsen said the initial lead compound needed to be improved with regard to both potency and safety.  Over 100 new chemical compounds had to be made before the team had one suitable for in vivo studies, he said.

The research was supported by 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. Fran Sargent also contributed to the research.

Read more:

The Search for Scleroderma’s “Off Switch”
http://www.med.umich.edu/scleroderma/pdf/scleroderma_research_brief.pdf

UMHS partners with local philanthropists to crowdfund the search for scleroderma’s cure
http://www.uofmhealth.org/news/archive/201304/scleroderma

Flipping the switch on scleroderma, Michigan State University
http://msutoday.msu.edu/news/2014/flipping-the-switch-on-scleroderma/

More about the Scleroderma Cure Fund:www.facebook.com/sclerodermafund

More about the U-M Scleroderma program: http://www.med.umich.edu/scleroderma/

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