An experimental drug called NU-9 has shown promise as an early intervention for Alzheimer’s disease. The corresponding study was published in Alzheimer’s & Dementia.
"Alzheimer's disease begins decades before its symptoms appear, with early events like toxic amyloid beta oligomers accumulating inside neurons and glial cells becoming reactive long before memory loss is apparent," said first author of the study, Daniel Kranz, a recent PhD graduate from the Department of Neurobiology at Northwestern University, in a press release.
"By the time symptoms emerge, the underlying pathology is already advanced. This is likely a major reason many clinical trials have failed. They start far too late. In our study, we administered NU-9 before symptom onset, modeling this early, pre-symptomatic window,” he added.
NU-9 was first conceived around 15 years ago as a molecule that could prevent the buildup of toxic protein aggregates in neurodegenerative diseases. The drug was found effective in animal models of amyotrophic lateral sclerosis (ALS) by 2021, and in 2024, received clearance from the US FDA to begin human trials for the condition.
Studies have also shown that NU-9 can effectively clear amyloid beta oligomers in lab-grown brain cells from the hippocampus, pointing towards the drug’s efficacy against Alzheimer’s disease.
In the current study, researchers investigated whether NU-9 could halt the progression of Alzheimer's disease when administered at its earliest stages. To do so, they administered the drug to a pre-symptomatic mouse model of the condition. Mice received a daily oral dose for 60 days.
Ultimately, NU-9 significantly reduced early reactive astrogliosis, an inflammatory reaction linked to early stages of the disease. Levels of toxic amyloid beta oligomers bound to astrocytes also decreased, alongside an abnormal form of the protein TDP-43, a marker of neurodegenerative diseases associated with cognitive impairment.
During the study, the researchers also identified a distinct amyloid beta oligomer subtype called ACU193+ which potentially instigates early Alzheimer's pathology. NU-9 targeted and reduced this subtype, suggesting the drug may be effective during the earliest stages of Alzheimer’s.
"If you have high cholesterol, it doesn't mean that you will have a heart attack soon. But it's time to take drugs to lower your cholesterol levels to prevent that heart attack from happening down the road. NU-9 could play a similar role. If someone has a biomarker signaling Alzheimer's disease, then they could start taking NU-9 before symptoms appear,” said co-author of the study, Richard Silverman, Professor at the Department of Chemistry at Northwestern University and inventor of NU-9, in a press release.
The researchers are testing NU-9 on additional models of Alzheimer’s disease, including an animal model of late-onset disease. They also intend to follow animals for longer periods of time to understand longer-term effects.
Sources: Science Daily, Alzheimer’s & Dementia
