A small molecule drug originally developed for ALS is now showing remarkable promise for Alzheimer’s disease, potentially revolutionizing treatment approaches for multiple neurodegenerative conditions.
At a Glance
- NU-9, developed at Northwestern University, targets underlying mechanisms of neurodegeneration rather than just disease symptoms
- The drug has received an additional $7.3 million grant from the National Institute on Aging to explore its potential for Alzheimer’s disease
- NU-9 works by reducing protein aggregates in brain cells, effectively “cleaning house” to restore neuron health
- The FDA has granted Investigational New Drug status, allowing Phase I clinical trials to begin
- Researchers believe NU-9 may benefit multiple neurodegenerative diseases due to their shared cellular problems
A Novel Approach to Neurodegenerative Disease
Northwestern University researchers have developed an experimental drug called NU-9 that is garnering significant attention in the field of neurodegenerative diseases. Originally designed to target amyotrophic lateral sclerosis (ALS), the drug has demonstrated promising results in animal models of Alzheimer’s disease. The National Institute on Aging recently invested an additional $7.3 million to further explore NU-9’s potential beyond ALS, recognizing its unique approach to treating the fundamental mechanisms of neurodegeneration rather than just addressing symptoms.
NU-9, a small molecule compound, was developed through the collaborative efforts of Northwestern chemist Richard B. Silverman and neurologist P. Hande Ozdinler. What makes this drug particularly noteworthy is its focus on improving neuron health by addressing common cellular problems across multiple neurodegenerative conditions. The drug has shown effectiveness in improving mitochondrial function, reducing endoplasmic reticulum stress, decreasing brain inflammation, and enhancing axon transport – issues that are prevalent in ALS, frontotemporal degeneration (FTD), and Alzheimer’s disease.
Richard Silverman’s newest #ALS drug, NU-9, has been found to effectively treat Alzheimer’s disease in a new animal study — offering hope for broad neurodegenerative therapies. #Alzheimers #ALS #Neurosciencehttps://t.co/3yVq6bG1jz
— Northwestern Chemistry (@NUChemistry) April 9, 2025
Clearing Cellular “Garbage”
The mechanism behind NU-9’s effectiveness is particularly intriguing. The drug targets protein aggregates – abnormal clumps of proteins that accumulate inside neurons and contribute significantly to their deterioration and death. These aggregates are common in various neurodegenerative diseases, including ALS, FTD, and Alzheimer’s disease. By reducing these harmful protein accumulations, NU-9 essentially helps neurons regain their health and functionality within brain circuitry.
Recent studies have revealed that NU-9 works by preventing the buildup of amyloid beta oligomers inside cells – a hallmark of Alzheimer’s disease. The drug appears to utilize lysosomes and the enzyme cathepsin B to break down these protein clumps effectively. Interestingly, NU-9 does not prevent protein formation outside cells, indicating that it primarily acts on intracellular processes. In cellular cultures and small mouse studies, NU-9 has demonstrated efficacy in reducing toxic protein buildup and improving performance in memory tests.
From Laboratory to Clinical Trials
The progress of NU-9 from laboratory discovery to potential clinical application has been remarkably swift. The drug has already received Investigational New Drug status from the FDA, allowing Phase I clinical trials to evaluate its safety and tolerability in humans. This represents a significant milestone in the drug development process and brings hope to millions affected by neurodegenerative diseases. The research team has expanded to include experts like William Klein, who specializes in Alzheimer’s disease, to further explore NU-9’s potential applications.
The promising results from NU-9 studies suggest a paradigm shift in how we approach neurodegenerative diseases. Rather than developing separate treatments for each condition, researchers are now exploring the possibility that shared mechanisms may link different neurodegenerative diseases. This approach could potentially allow drugs like NU-9 to treat multiple conditions, streamlining treatment development and improving outcomes for a broader range of patients. Researchers are already planning to explore NU-9’s effectiveness in other neurodegenerative conditions like Parkinson’s and Huntington’s disease.
