ALS Research Partnership Showing Promising Results

ALBANY, N.Y. (May 27, 2021) – Research on a potential therapy for amyotrophic lateral sclerosis (ALS) that’s taking place in a UAlbany chemistry lab on campus is showing promising results.

ALS, also known as Lou Gehrig’s Disease, is a progressive neuromuscular disease that slowly robs patients of their ability to walk, talk, move and even breathe independently, explains Li Niu, chemistry professor and researcher who is also affiliated with the University’s RNA Institute. Approximately 90 percent of cases have no known genetic link or family history, leaving the disease as baffling to experts as it is devastating to victims. May is designated as ALS month, to raise awareness of the disease and the research into treatment options.

ALS currently has no cure and there are only two drugs approved by the FDA to potentially slow the progression, though their level of success is low, said Niu. Because the hallmark of the disease is the death of motor neurons in the spinal cord and lower brain stem, the hope for a more effective treatment or even a cure is dependent on the success of halting the death of those motor neurons – something that Niu’s lab has been working on for more than a decade and is reporting encouraging results.

Inspired by a mentor who was afflicted with ALS, Niu has used his expertise as a bio- and neurochemist to work on a National Institutes of Health funded project aimed at developing a class of RNA molecules or RNA aptamers (molecules that bind to a specific target molecule) as potential drug candidates designed to block the death of the motor neurons that connect the brain to muscles. His earlier work was funded by the Department of Defense and the Muscular Dystrophy Association. 

“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.”

There are several theories regarding glutamate receptors in ALS that are helping to guide the research, said Niu. Some have to do with the amount or a higher activity level of the receptors, while another theory is that an abnormal receptor form is generated in these motor neurons and these receptors, which are channel proteins, allow more calcium to get into the cells. This is a problem, said Niu, because too much calcium in a neurological context causes neurodegeneration and cell death; this is the theory that his lab primarily works from.

Working with many current and past graduate [HMB1] and undergraduate students in his lab as well as an ALS physician and researcher at the University of Tokyo School of Medicine, Li is developing RNA aptamers that aims to regulate the glutamate receptor activities and prevent calcium from getting into and accumulating inside the cells. His partner lab in Japan has been testing these RNA aptamers on an ALS mouse model, and the results thus far are promising. One of the RNA aptamers Li developed is shown to be effective in stopping motor neuron cell death and rescuing dying neurons - and the animals are showing improved motor function following the aptamer treatment. The aptamer is not only effective, but also does not cause any side effects when it is injected directly into the spinal cord. 

Li stressed that while this is incredibly promising, the drug is being tested in ALS models and more research is needed before the testing can be done on humans with ALS.

“Before we bring the drug candidate forward for human trials, we have to do more testing,” he said. “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. But I’m optimistic that this could provide a real impact on patients suffering with ALS.”