Grant supports animal testing of RNA molecules in familial ALS
Work in sporadic ALS model suggested therapy protects neurons, motor skills
A grant given to a researcher at the University of Albany in New York will support further work into specific RNA molecules, called RNA aptamers, that have shown early promise in treating amyotrophic lateral sclerosis (ALS).
The $768,825 U.S. Department of Defense award to Li Niu, PhD, a chemistry professor and researcher at the university’s RNA Institute, will advance studies into molecules that target excessive glutamate signaling, which has been implicated in the disease.
Niu plans to test RNA aptamers in animal models of familial ALS. Previous studies by his lab in mice models of sporadic ALS showed a potential to protect motor neurons and improve the animals’ motor function.
“Because the hallmark of the disease is the death of motor neurons in the spinal cord and lower brain stem, the hope for more effective treatment, or even a cure, depends on finding a way to halt the death of those motor neurons — something that our lab has been working on for more than a decade with encouraging results,” Niu said in a university press release.
ALS research into RNA aptamers to prevent glutamate damage to motor neurons
ALS is caused by the progressive loss of motor neurons, the nerve cells that control movement, leading to such disease symptoms as muscle weakness and shrinkage.
While the mechanisms leading to the death of motor nerve cells remain largely elusive, research has identified the accumulation of glutamate, a chemical messenger, in the brain and spinal cord as a potential contributor.
Glutamate is a neurotransmitter, or a signaling molecule that nerve cells use to communicate with other cells. It works by binding to specific receptors — called glutamate receptors — that are uniquely found in the brain and spinal cord.
Glutamate’s binding to its receptors unleashes a calcium flow that activates nerve cells. However, elevated glutamate leads to overexcitation and calcium overload in motor neurons, which can be toxic.
Niu and his team have been developing RNA aptamers — short RNA molecules that bind to their target with high affinity and specificity, much like antibodies — that can bind to glutamate receptors and prevent their overactivation in motor neurons.
Supported by funds from the National Institutes of Health, and other funding agencies, the team has developed and tested several RNA aptamers.
In the sporadic ALS mouse model, they showed an ability to halt nerve cell death and promote the repair of damaged neurons when injected directly into the animals’ spinal canal. Mice given the aptamer treatment also showed better motor function.
With the recent grant, researchers will conduct similar experiments in mice carrying a familial ALS mutation, helping them understand if their RNA aptamers are able to slow disease progression in both forms of the disease.
“For many years, our lab has worked to identify these special RNA molecules or RNA aptamers from a large RNA library and test them in cells that express glutamate receptors. This new funding will allow us to extend our work,” Niu said.
“If we can demonstrate that these RNA molecules are effective in preventing motor neuron death without inducing significant side effects in these ALS animal models, we hope to next bring these RNA molecules to a clinical trial,” he added. “I am optimistic that our research could make a positive impact on patients.”
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