The projects will investigate ALS mechanisms of disease, genetic causes, and pinpoint new therapy targets that can be used to develop better treatments. The funding also will support the discovery of new biomarkers that are necessary to conduct successful clinical trials.
Other than the U.S. government, MDA is the largest funding source for neuromuscular disease research. MDA supports a large network of more than 150 top national medical institutions and has invested more than $165 million dollars in ALS research.
One project, led by Thomas Gaj, PhD at the University of Illinois, will evaluate the potential of a new gene-editing technique to correct mutations in the superoxide dismutase 1 gene (SOD1), the cause of about 2% of all ALS cases.
Tania Gendron, PhD, at the Mayo Clinic, will investigate the potential of protein biomarkers in ALS patients’ blood and cerebrospinal fluid (the liquid bathing the brain and spinal cord) to identify patients at higher risk for developing cognitive impairments. This information may help tailor treatment and help design more effective clinical trials.
Csaba Konrad, PhD, at Weill Cornell Medical College also will try to identify new biomarkers for predicting disease progression and response to therapy. Konrad will analyze a large biobank of skin cells from non-familial ALS patients for cells’ size and shape, and whether these parameters can identify clusters of patients based on progression and therapy response.
Jonathan Glass, MD, at Emory University, will expand the Northeast ALS Consortium’s (NEALS) biobank for tissues and fluids from ALS patients available to the research ALS community. The NEALS Consortium is an international organization of 125 research sites collaborating to enhance clinical research in ALS and other motor neuron diseases.
The researcher will investigate how the mutation in this gene affects the metabolism of RNA (the chemical cousin of DNA) specifically how it may promote the accumulation of toxic RNA aggregates, culminating in the death of motor neurons in an ALS animal model.
Marka Van Blitterswijk, MD, PhD, in collaboration with Mark Ebbert, PhD, both at the Mayo Clinic will evaluate how the size of the repeats in the C9ORF72 gene and whether interruptions in the repeats affect disease progression. Using a novel technique, the researchers will evaluate how the repeat parameters can help identify patients at higher risks for death and impaired cognition.
The project led by John Landers, PhD, at the University of Massachusetts Medical School, will use a genetic approach to identify new gene targets for ALS therapies. Researchers will perform an RNA interference (RNAi) screen — the RNA molecules will “silence” one gene at a time — and look at which gene targets are the best candidates for future ALS-targeted therapies.
Ze’ev Melamed, PhD, of the Ludwig Institute for Cancer Research, will investigate further the role of stathmin-2 (STMN2) protein in non-familial ALS. A recent study showed that the levels of STMN2 — which is necessary for neuron growth and regeneration — are decreased in ALS, strengthening its potential as a new therapeutic target.
“These new grants show MDA’s commitment to fund groundbreaking research that will one day lead to treatments and cures for ALS,” Amanda Haidet-Phillips, MDA director, said in a press release.
“Every grant will have an impact on therapy development, from improving understanding of disease mechanisms to discovering new therapeutic targets and moving these into clinical trials,” Haidet-Phillips said.
Latest results in ALS research, including the ones funded by MDA, will be shared this month by more than 1,000 neuromuscular disease scientists, clinicians, regulators and advocates, at the Annual MDA Clinical and Scientific Conference “Progress in Motion,” April 14-17, Orlando, Florida.