Jeffrey Rothstein, professor of neurology and neuroscience at Johns Hopkins University in Baltimore, Md., was awarded an MDA research grant totaling $392,706 over a period of three years to study the most common genetic cause of amyotrophic lateral sclerosis (ALS), using cells derived from patient skin samples.
“Understanding the pathophysiology of and developing new therapeutics for ALS and dementias such as Alzheimer’s disease and frontotemporal dementia has been an enormous challenge,” Rothstein says. Among the biggest roadblocks has been the difficulty of developing appropriate models of the disease — ones that closely parallel the human condition.
A new technique to overcome this barrier is the use of induced pluripotent stem cells (iPS cells). These cells can be taken from the skin of an individual with ALS and treated with growth factors to return them to a less differentiated state. From this stem-cell-like condition, they can then be induced to develop into any cell type, including muscle-controlling nerve cells called motor neurons or other cells of the central nervous system.
Rothstein plans to use iPS cells from people whose ALS is caused by a mutation in the C9ORF72 gene, the most common genetic cause of ALS. By comparing these cells to cells from unaffected individuals, Rothstein hopes to find a molecular signature for the disease-causing effects of the mutant gene. That signature, or biomarker, can then be used to quickly assess the effects of potential therapies on the cells. “The use of these human cells may allow us to efficiently and quickly develop a drug therapy for the C9ORF72 form of ALS,” he says.
Funding for this MDA grant began Feb. 1, 2013.