Giovanni Manfredi, professor of neurology and neuroscience at Weill Medical College of Cornell University in New York, N.Y., was awarded an MDA research grant totaling $355,317 over a period of three years to study whether calcium imbalance in nervous system support cells called astrocytes contributes to amyotrophic lateral sclerosis (ALS).
The death of muscle-controlling nerve cells called motor neurons cause the symptoms of ALS, but in recent years it has become clear that astrocytes contribute to the death of motor neurons. Astrocytes normally help motor neurons; and how and why they harm them in ALS is unknown.
“We have developed a novel hypothesis to explain the mechanisms of astrocyte toxicity in familial ALS, which involves intracellular calcium signaling,” Manfredi says. Calcium serves as an internal sensor for regulating many cellular functions. “All cells, including astrocytes, have to keep calcium levels in check at all times.”
His work has suggested that changes within the astrocyte lead to impaired calcium regulation and secretion of toxic molecules, which in turn cause motor neuron death. He plans to further test this hypothesis by manipulating the amount of oxidative stress to which astrocytes are exposed, both in cell culture and in animal models, and studying how they handle calcium in response. His preliminary work has identified a protein that may be centrally involved in regulating calcium in astrocytes, and he will further study this protein to determine if it is a potential target for therapy.
“Numerous exciting reports have emerged in ALS research in the past few years, strongly suggesting that ALS is the product of the combined action of multiple cell types in the nervous systems, including neurons and glial cells,” Manfredi says. (Astrocytes are a type of glial cell.) “These new developments in ALS research will accelerate the understanding of the disease and the development of effective therapies.”
Funding for this MDA grant began Feb. 1, 2013.