‘Remarkable’ ALS Drug May Also Work on Alzheimer’s – ryan

A drug originally developed to treat a rare neurological disease that weakens nerve cells in the brain and spinal cord may also hold promise for combating Alzheimer’s, according to new research from Illinois’s Northwestern University.

The compound, NU-9, has been approved by the U.S. Food and Drug Administration (FDA) for clinical trials in the treatment of amyotrophic lateral sclerosis (ALS), also known as “Lou Gehrig’s disease”.

Now, however, NU-9 has shown the ability to improve neuron health and memory in animal models of Alzheimer’s disease.

According to the Alzheimer’s Association, there are some seven million Americans living with the brain disorder, which slowly destroys memory and thinking skills, eventually leading to the inability to perform simple tasks.

By 2050, this number is projected to rise to nearly 13 million.

“This drug is quite remarkable that it works in these multiple systems,” said Richard B. Silverman, the Northwestern chemist who invented NU-9, in a statement.

“We need to test it in humans before we know how effective it is in treating Alzheimer’s disease. But how well upper motor neurons function in mice is similar to how well they function in humans. So, it seems to me, NU-9 really should work.”

Unlike drugs that focus on symptoms, NU-9 appears to treat the underlying mechanisms common to multiple brain diseases: the buildup of misfolded proteins that lose their normal shape and start to stick together, harming brain cells.

Promising Results in Lab and Animal Studies

In their study, the team found that NU-9 improved memory performance in Alzheimer’s mouse models and helped neurons clear toxic protein clusters in both cell cultures (cells grown in the lab) and animal experiments.

“What our study demonstrates is that the same mechanism affects two totally different proteins in two totally different diseases,” said paper co-author William Klein in statement.

“In both diseases, cells suffer from toxic protein buildup. It appears there is a common mechanism that gets rid of these proteins to prevent them from clustering. NU-9 is rescuing the pathway that saves the cell. It’s very exciting.”

Inventors With a Proven Track Record

Silverman, who previously invented pregabalin (Lyrica)—a widely used drug for nerve pain, seizures and fibromyalgia—is the Patrick G. Ryan/Aon Professor of Chemistry at Northwestern and founder of Akava Therapeutics, which is commercializing NU-9.

Klein, an expert on Alzheimer’s disease, is a professor of neurobiology and cofounder of Acumen Pharmaceuticals, which has a therapeutic antibody for Alzheimer’s currently in clinical trials.

Clearing Protein Clumps and Reducing Inflammation

With Alzheimer’s, amyloid beta oligomers—small clusters of a brain protein called amyloid beta that become sticky and toxic—build up and attach to brain cells, interfering with how the brain works and eventually killing cells.

“These are good proteins gone bad,” said Klein. “They are good proteins, but when they clump together, they play a role in their own build up. They stick to the cells, to the nearby cells and to the synapses. That causes brain dysfunction and, ultimately, brain cell death.”

In lab tests, NU-9 was shown to reduce this buildup inside cells and along neuron branches, called dendrites, which are structures that help cells receive messages from other brain cells. Even after the drug was removed, the protective effect remained.

The study also found that brain inflammation—the body’s immune response in the brain that can cause further damage—was significantly reduced.

“Inflammation of the brain was prevented or greatly reduced by the treatment of NU-9,” Klein said. “It stops the amyloid beta oligomer buildup, and also stops the consequences of neuroinflammation, which causes a lot of damage in the brain. So, the drug is very powerful on two levels: cellular and whole animal.”

Unlocking the Cell’s Cleanup Crew

Further research showed NU-9 may work by activating lysosomes, which are small structures inside cells that act like recycling centers, breaking down and disposing of waste. It also uses the help of an enzyme called cathepsin B, which helps digest unwanted proteins.

“Cells have two important ‘junk compartments’: the lysosome and the proteasome,” Silverman said. “They collect junk and other components that are not useful to the cell, chew them up and get rid of them.

“We found the proteasome wasn’t involved at all. It’s the lysosome that plays a role in how NU-9 works. But we’re still trying to figure out exactly what NU-9 binds to in order to trigger the lysosome.”

“It’s a black box phenomenon,” added Klein. “It’s like a relay race for moving these toxic clustered proteins around the cell. The proteins are clustered in one vesicle and then another vesicle and then finally handed off to the lysosome. We think NU-9 targets something in the early stage of that relay, but we don’t know exactly what the target is.”

The Road Ahead

While the early results are encouraging, researchers emphasize that more testing is needed. Klein noted the need for more rigorous memory tests, and Silverman hopes to further optimize the compound. The team also plans to test NU-9 on other diseases like Parkinson’s, which affects movement, and Huntington’s, a genetic disorder that causes the breakdown of brain cells.

“It has long been thought that every neurodegenerative disease is a completely separate disease, but our findings suggest that common mechanisms might connect them,” said Silverman.

“This discovery opens the door to a new family of therapeutic compounds that, like NU-9, could control multiple degenerative diseases at a point before major damage to cells begins.”

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Correction 09/04/25, 10:02 a.m. ET: This article has been updated to reflect the fact that the NU-9 is not in clinical trials, but has been approved for trials by the FDA.

Reference

Johnson, E. A., Nowar, R., Viola, K. L., Huang, W., Zhou, S., Bicca, M. A., Zhu, W., Kranz, D. L., Klein, W. L., & Silverman, R. B. (2025). Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases. Proceedings of the National Academy of Sciences, 122(10).