New drug for Alzheimer’s ‘highly promising’ when given early

(CN) — For more than a hundred years and before the diseases were fully understood, Alzheimer’s and dementia were, and continue to be, harrowing prospects for aging adults.

A new study published on Thursday in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association provides new evidence for a lasting treatment to Alzheimer’s, pinpointing early-onset symptoms and intervention through a medication regimen.

A research team at Northwestern University conducted medical trials on mice and the experimental drug NU-9 looked promising as a potential treatment. The drug decreased toxic clusters of peptides that tend to start early changes in the brain of an Alzheimer’s patient, such as inflammation and an immune cell response.

“As an orally administered drug capable of blocking the earliest pathological events in an animal model by a new mechanism, it represents a highly promising therapeutic candidate,” Northwestern University doctoral graduate and lead author of the study Daniel Kranz said in an email about NU-9’s ability to treat Alzheimer’s.

“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,” Kranz said in a statement

“In our study, we administered NU-9 before symptom onset, modeling this early, pre-symptomatic window.”

Along with his adviser William Klein, an expert on Alzheimer’s disease and a professor of neurobiology at the Weinberg College of Arts and Sciences at Northwestern, Kranz and a group of researchers evaluated the efficacy of NU-9 with pre-symptomatic mice. He found that, if given an oral dose of NU-9 for 60 days, the drug reduced an inflammatory reaction that presents before symptoms.

Also, it decreased the numbers of toxic clumps of protein that bind with astrocytes — star-shaped brain cells that curb inflammation and protect neurons.

Furthermore, the protein TDP-43 — in its abnormal form it is a sign of neurodegenerative diseases that often cause cognitive damage — was also greatly reduced.

“These results are stunning,” Klein said in a statement accompanying the study. “NU-9 had an outstanding effect on reactive astrogliosis, which is the essence of neuroinflammation and linked to the early stage of the disease.”

Klein is a co-founder of Acumen Pharmaceuticals, a company currently conducting clinical trials and in development for an antibody that targets the proteins, called amyloid beta oligomers, found in the study.

According to the researchers, the improvements from NU-9 cover different sections of the brain, having a widespread anti-inflammatory effect.

While collecting data, Kranz and his colleagues found a particular subtype of the proteins that are often more toxic than those that form plaques — another kind of protein clump that builds up between neurons, disrupting cell communication, and generally found in the later stages of Alzheimer’s.

The subtype, called ACU193 for the antibody that detected it, is typically found inside agitated neurons, the scientists said. When attached to astrocytes, they begin to spread inflammation throughout the brain, far earlier than when memory loss generally starts in a patient.

Overall, Kranz said, NU-9 is a “well-suited” medication for daily use and rids the brain of harmful neurotoxins.

A co-author of the study, Richard Silverman, is also a founder of Akava Therapeutics, a startup bringing NU-9 to the pharmaceutical market. Silverman invented NU-9 and previously invented a medication to treat fibromyalgia, epilepsy and nerve pain.

Cases of Americans over 65 years old diagnosed with Alzheimer’s are expected to surge in the next few decades, almost doubling from current estimates of 6.7 million people to 14 million by 2060, according to the U.S. Centers of Disease Control and Prevention.

For Kranz, his future work regarding NU-9 is clear.

“The next steps are to extend the treatment period to assess long-term outcomes and evaluate the behavioral effects of NU-9, as well as to test the compound in a rabbit model of late-onset Alzheimer’s disease.”