Investigational RNA Molecule May Slow ALS Progression

An investigational RNA molecule called an RNA aptamer halted the death of motor neurons and helped preserve motor function in a mouse model of amyotrophic lateral sclerosis (ALS).

Further research is ongoing to confirm the findings in additional ALS models before testing it in humans, “but I’m optimistic that this could provide a real impact on patients [living] with ALS,” Li Niu, PhD, chemistry professor and researcher at the University of Albany’s RNA Institute, said in a press release.

ALS is characterized by the progressive loss of motor neurons, the specialized nerve cells that send electrical signals from the central nervous system (CNS) — the brain and spinal cord — to muscles, controlling their function.

While the underlying causes of motor neuron death remain elusive, it is likely that a group of factors contribute to damaging these cells, leading to their death. One such factor is the accumulation of the chemical messenger glutamate in the brain and spinal cord, which produces an overwhelming activation of nerve cells that is toxic.

Glutamate exerts its effects by binding to specific receptors — called glutamate receptors — that are uniquely produced by nerve cells in the brain and spinal cord and activate them by allowing calcium to flow.

Initially funded by the U.S. Department of Defense and the Muscular Dystrophy Association, Niu and his team developed specific RNA molecules — RNA aptamers — that bind to glutamate receptors and prevent calcium overload within motor neurons, potentially slowing ALS progression.

“We’re focusing on a particular group of receptors that are uniquely expressed in the brain and spinal cord, called glutamate receptors, which are responsible for things like memory, learning and are indispensable for brain development,” said Niu. “If anything goes wrong with these receptors, it causes so many problems — which is why we want to focus on those receptors specifically.”

With additional funding from the National Institutes of Health, Niu now is working in partnership with an ALS physician and a researcher at the University of Tokyo School of Medicine, in Japan, who are testing the RNA aptamers in a mouse model of ALS. The RNA therapy is injected directly into the animals’ spinal cords.

Early results are promising. One of the RNA aptamers developed in Niu’s lab effectively halted the death of motor neurons and rescued dying nerve cells, leading to improved motor function. Notably, no side effects were registered following the spinal cord injection.

Preclinical research in additional ALS models is ongoing to confirm the promising results before any testing is conducted in humans.

“Before we bring the drug candidate forward for human trials, we have to do more testing,” said Li. “If we can confirm these are safe and do not induce side effects, we are hoping to receive funding to launch clinical trials to see whether we can bring this treatment forward.”