Published April 26, 2013
A potential new treatment strategy for patients with Charcot-Marie-Tooth disease is on the horizon, thanks to research by neuroscientists now at the University at Buffalo’s Hunter James Kelly Research Institute and their colleagues in Italy and England.
The institute is the research arm of the Hunter's Hope Foundation, established in 1997 by Jim Kelly, Buffalo Bills Hall of Fame quarterback, and his wife, Jill, after their infant son Hunter was diagnosed with Krabbe Leukodystrophy, an inherited fatal disorder of the nervous system. Hunter died in 2005 at the age of eight. The institute conducts research on myelin and its related diseases with the goal of developing new ways of understanding and treating conditions such as Krabbe disease and other leukodystrophies.
Charcot-Marie-Tooth or CMT disease, which affects the peripheral nerves, is among the most common of hereditary neurological disorders; it is a disease of myelin and it results from misfolded proteins in cells that produce myelin.
The new findings were published online earlier this month in The Journal of Experimental Medicine.
They may have relevance for other diseases that result from misfolded proteins, including Alzheimer’s disease, Parkinson’s, multiple sclerosis, Type 1 diabetes, cancer and mad cow disease.
The paper shows that missteps in translational homeostasis, the process of regulating new protein production so that cells maintain a precise balance between lipids and proteins, may be how some genetic mutations in CMT cause neuropathy.
CMT neuropathies are common, hereditary and progressive; in severe cases, patients end up in wheelchairs. These diseases significantly affect quality of life but not longevity, taking a major toll on patients, families and society, the researchers note.
“It’s possible that our finding could lead to the development of an effective treatment not just for CMT neuropathies but also for other diseases related to misfolded proteins,” says Lawrence Wrabetz, MD, director of the institute and professor of neurology and biochemistry in UB’s School of Medicine and Biomedical Sciences and senior author on the paper. Maurizio D’Antonio, of the Division of Genetics and Cell Biology of the San Raffaele Scientific Institute in Milan is first author; Wrabetz did most of this research while he was at San Raffaele, prior to coming to UB.
When cells recognize that the misfolded proteins are being synthesized, cells respond by severely reducing protein production in an effort to correct the problem, Wrabetz explains. The cells commence protein synthesis again when a protein called Gadd34 gets involved.
And while CMT is the focus of this particular research, the work is helping scientists at the Hunter James Kelly Research Institute enrich their understanding of myelin disorders in general.
“What we learn in one disease, such as CMT, may inform how we think about toxins for others, such as Krabbe’s,” Wrabetz says. “We’d like to build a foundation and answer basic questions about where and when toxicity in diseases begin.”
Funding was provided by the National Institutes of Health, the European Community and an award to D’Antonio from the Italian Ministry of Health.
Thank you so much for the hard work! My husband is 74 and my son is 50. Both have CMT and my son has a lot of pain with his -- had a surgery to reconstruct his entire foot and ankle, and it was a terrible mistake. He has had severe pain every since, so he didn't get the other foot done. My husband is getting in a terrible shape -- lost motor skills, hearing and can't walk very good with walker. I live with hope of a breakthrough and LOTS OF PRAYERS.