New treatment stops progression of Alzheimer’s disease in monkey brains – sciencedaily

Led by researchers at NYU Grossman School of Medicine, the survey showed that aged monkeys had up to 59% less plaque deposits in their brains after treatment with CpG oligodeoxynucleotides (CpG ODN), compared to untreated animals. These beta-amyloid plaques are fragments of proteins that clump together and block the junctions between nerve cells (neurons).

The brains of the treated animals also showed decreased levels of toxic tau. This nerve fiber protein can destroy nearby tissue when disease-related changes in its chemical structure cause it to cling to other cells.

“Our results show that this therapy is an effective way to manipulate the immune system to slow down neurodegeneration,” says Akash Patel, MS, assistant researcher at the Center for Cognitive Neurology at NYU Langone Health.

Investigators say the treatment also resulted in cognitive benefits. When presented with a series of puzzles, the elderly monkeys given the drug performed similarly to young adult animals and much better than their untreated age group. The treated monkeys also learned new puzzle-solving skills faster than their untreated peers.

Previous treatment efforts targeting the immune system have failed because the drugs overstimulated the system, causing dangerous levels of inflammation that can kill brain cells, the researchers say.

“Our new treatment avoids the pitfalls of previous attempts because it is administered in cycles, giving the immune system a chance to rest between doses,” says study co-lead author Thomas Wisniewski, MD. He notes that no additional inflammation was observed in the treated monkeys. Wisniewski is Professor Gerald J. and Dorothy R. Friedman in the Department of Neurology and Director of the Center for Cognitive Neurology at NYU Langone.

Alzheimer’s disease is the sixth leading cause of death in the United States and has no known cure. Drug therapies designed to slow or manage symptoms have failed, says Wisniewski, also director of the Alzheimer’s Research Center at NYU Langone. A growing body of evidence has implicated the immune system, the set of cells and proteins that defend the body against invading bacteria and viruses, as a contributor to Alzheimer’s disease. A subset of immune cells, those of the innate immune system, swallow and remove debris and toxins from body tissue as well as invading microbes. Studies have shown that these immune gatekeepers become sluggish as a person ages and fail to remove the toxins that cause neurodegeneration.

The new survey, published on the cover on June 15 in the journal Brain, is the first to target the innate immune system with potential therapy for the disorder in monkeys, according to Wisniewski. CpG ODN drugs are part of a class of innate immune regulators that accelerate these depleted immune guardians. He says the research team is also the first to use the “pulse” drug delivery technique to prevent excessive inflammation, immune responses such as swelling and pain that result from immune cell testing. sites of injury or infection. Although necessary for immune defenses and healing, too much inflammation contributes to many disease mechanisms.

For the investigation, the research team studied 15 female squirrel monkeys between the ages of 17 and 19. Eight received a single dose of the drug once a month for two years, while the rest were given saline instead. The researchers observed the behavior of the two groups and compared samples of brain tissue and blood for plaque deposits, tau protein levels, and signs of inflammation.

Wisniewski notes that as they age, virtually all squirrel monkeys naturally develop a form of neurodegeneration that mimics Alzheimer’s disease in humans, making them ideal for studying the disease.

“The aging similarities between the animals studied and our own species give us hope that this therapy will also work in human patients,” said study co-author Henrieta Scholtzova, MD, PhD.

Scholtzova, an associate professor in the NYU Langone department of neurology, warns that the researchers only evaluated aged monkeys that already showed significant signs of neurodegeneration. Further testing on younger animals, she notes, would allow them to assess the effectiveness of treatment in the early stages of the disease.

Scholtzova says the team next plans to start testing CpG ODN therapy on human patients with mild cognitive impairment or in the early stages of dementia. They also intend to study this treatment in associated neurodegenerative diseases.

Funding for the study was provided by grants from the National Institutes of Health NS102845, NS079676, AG066512, and OD01 093840; grant from the Alzheimer’s Association AARG 16440596; and a Cattleman for Cancer Research grant. Wisniewski and Scholtzova were granted a patent for therapies developed from this therapeutic approach, from which the researchers and NYU Langone could benefit financially. The patents were licensed to Empriver of Southborough, Mass. All of these relationships are managed in accordance with NYU Langone policies and procedures.