Northwestern University's experimental drug NU-9, initially recognized for its potential in reversing amyotrophic lateral sclerosis (ALS), is now under investigation for its effectiveness in treating other neurodegenerative diseases such as Alzheimer's disease and frontotemporal degeneration (FTD). The National Institute on Aging (NIA) has committed an additional $7.3 million to further explore the drug's capabilities.
Targeting Shared Mechanisms of Neurodegeneration
NU-9's mechanism of action targets the underlying causes of neurodegeneration, such as misfolded proteins, rather than addressing specific disease symptoms. P. Hande Ozdinler, principal investigator of the NIA grant and an associate professor of neurology at Northwestern University Feinberg School of Medicine, explained that ALS, FTD, and Alzheimer's share common cellular problems, including mitochondrial dysfunction, endoplasmic reticulum stress, brain inflammation, and axon transport issues. "If NU-9 is effective against those problems in ALS, it makes sense that it would also be effective in similar diseases," Ozdinler stated.
Preclinical Success in Animal Models
Previous studies have demonstrated NU-9's ability to improve the health of diseased neurons in animal models of ALS. After 60 days of treatment, the health of diseased neurons in mice treated with NU-9 became comparable to that of healthy controls. A study published in Scientific Reports in 2022 showed that NU-9 lengthened the axons of diseased upper motor neurons in an ALS mouse model. Earlier research in Clinical and Translational Medicine in 2021 highlighted NU-9's ability to improve the health of mitochondria and the endoplasmic reticulum in neurons.
Clinical Development and Future Trials
Richard B. Silverman, the Northwestern University chemist who invented NU-9, founded Akava Therapeutics to advance the drug's clinical development. NU-9, now called AKV9, has received Investigational New Drug status from the FDA, paving the way for Phase I trials to evaluate its safety and tolerability in healthy human subjects. Pending the FDA's review of Phase I results, a Phase II trial to assess the drug's efficacy in ALS patients is planned.
Addressing Protein Aggregation
Protein aggregation, a common feature in ALS, FTD, and Alzheimer's disease, leads to toxicity and eventual cell death. Ozdinler likened protein aggregates to "garbage inside a house," explaining that NU-9 works by "cleaning the house" and restoring neuronal health within the brain circuitry.
William Klein, a Northwestern University professor of neurobiology and expert on Alzheimer's disease, has joined the research team to further investigate NU-9's potential. Silverman noted the lengthy process of drug discovery and development, estimating it could take 10 to 12 years to bring a new drug to market. "But this drug has us very excited and hopeful about its potential to improve the lives of ALS and other neurodegenerative disease patients who have been without hope for so long," he said.
