UNIVERSITY OF MICHIGAN & MICHIGAN STATE UNIVERSITY SCIENTISTS BELIEVE THEY MAY HAVE FOUND SCLERODERMA’S ‘OFF SWITCH’
Scientists at the University of Michigan Health System & Michigan State University are optimistic that newly discovered compounds hold the key to treating and possibly even reversing the devastating effects of scleroderma, as well as other deadly fibrotic diseases. ANN ARBOR, MI
CHIGAN — March 21, 2013 — Researchers have just begun the initial stages of animal testing, but already believe that innovative new compounds hold promise for shutting down the progression of scleroderma in humans, right at its source. Scleroderma is a crippling autoimmune disorder that affects more than 300,000 people in the U.S. alone. It is characterized by a thickening and hardening of the skin that is so severe, it literally steals away the use of patients’ fingers, hands and limbs. As it advances across its victims bodies, the uncontrolled growth of fibrous tissue can also severely damage patients’ hearts, lungs and other organs, often leading to a prolonged and painful death. Scleroderma is one of most deadly disorders treated by rheumatologists.
“Currently there are no good treatments for scleroderma and no cure,” says Dinesh Khanna, M.D., M.S. Associate Professor of Internal Medicine and Director of the U-M Scleroderma Program. “But the promise of this research makes me very hopeful. It could mean a huge improvement in the quality of life and function for scleroderma patients here at the University of Michigan and around the world.”
The breakthrough originated in the lab of Rick Neubig, M.D., Ph.D., Professor of Pharmacology and Associate Professor of Internal Medicine in the U-M Medical School. Neubig also heads the U-M Center for the Discovery of New Medicines. What Neubig and his team did was develop a fundamentally unique approach to stopping the reaction that leads to the disease in the first place. “Most of the ways researchers have tried to treat scleroderma in the past, have revolved around blocking the initial inflammation,” says Neubig. “But just cutting off the inflammation does not stop the progression of the associated fibrosis, the aspect of scleroderma which is caused by overproduction of collagen. Our compounds target a genetic switch that controls the formation of myofibroblasts — which are the cells that produce too much collagen leading to the thickening of the skin and damage to other organs.” Neubig’s approach effectively blocks scleroderma by starving it of what it requires to exist in the first place — an overproduction of collagen.
“If we’re successful, scleroderma may not be the only disease to be affected by this discovery. Other conditions, like idiopathic pulmonary fibrosis and Crohn’s disease, also have the potential to be slowed, stopped or even reversed by this approach”, Neubig adds. Oftentimes, revolutionary new developments in medicine emerge out of unrelated research, as was the case with this discovery. Neubig’s compounds were initially identified in a high-throughput screening process focused on
cancer treatment, then optimized and tested in a lab environment. “We have begun testing those compounds in fibroblasts from scleroderma patients, and are very enthusiastic about their potential to treat and possibly to reverse scleroderma based on the results we’ve seen so far.”
The next steps, says Neubig, will be to expand testing in patient cells, continue to improve and refine the compounds, and most importantly demonstrate success in rodent models (in vivo). “Showing that they really work in vivo is the critical next step toward translating it for use in human patients,” he says. David Fox, M.D., who heads U-M’s Division of Rheumatology, agrees that Neubig’s initial efforts are very promising, and hopes for widespread support of the University’s fundraising efforts to help fund continued success in the laboratory and critical in vivo studies for Neubig’s compounds. “Given the difficult environment for federal research funding, we are seeking philanthropic support from the scleroderma community to accelerate the completion of the laboratory and in vivo research and, hopefully, speed a treatment to patients in desperate need of a cure.” says Fox. To support fundraising efforts, U-M has created a special Scleroderma Cure Fund and online giving page to accept donations to directly support the next stage of research and development for Neubig’s important compounds. “Over $500,000 will be required to take our research to the next level” says Fox, “we’re hoping that individuals who have been impacted by this terrible disease will rally in support of our research by donating to the Scleroderma Cure Fund online.”
Online donations can be made through either university at the following links:
U of M: http://ow.ly/n5Idi
MSU: http://ow.ly/ncDjj
“We need to expand the cell culture studies, greatly expand the research in animal models, including looking at the ability of these compounds to target fibrosis in the lungs — the most deadly aspect of the disease — and also refine the delivery method to ensure it will be well-tolerated,” Fox says. Fox cautions that even if Neubig’s compounds are successful in in vivo trials and are able to move forward to the next stage, human trials could still be a ways away. “A few years may sound like a long time,” he adds, “but when you’re talking about something that has the potential to dramatically improve the quality of life for hundreds of thousands of patients who may suffer and die because of scleroderma, it’s important to take the time to get the science right.”
The University of Michigan has filed for patent protection for the discovery and is currently looking for a licensing partner to help bring it to market.

U-M Scleroderma Program: http://med.umich.edu/scleroderma
Support the research:
U of M: http://ow.ly/n5Idi
MSU: http://ow.ly/ncDjj
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