• A drug doctors use to treat multiple sclerosis may be effective in treating Alzheimer’s symptoms, including memory loss.
• In mice, memory improved after 8 weeks of treatment with the drug.
• The treated mice also showed a reduction in amyloid plaques.
• Clinical trials are needed to show whether the drug, glatiramer acetate, can slow the development of Alzheimer’s disease.

Alzheimer’s disease (AD) affects 1 in 9 people aged 65 and older in the United States and 1 in 14 people in this age group in the United Kingdom. Memory loss is one of the most troubling symptoms of AD. A study published in Frontiers in Neuroscience has found that a drug used to treat multiple sclerosis (MS) may help alleviate this symptom.

Researchers from the Del Monte Institute for Neuroscience at the University of Rochester, NY, carried out the study in mice. The scientists gave the drug, glatiramer acetate (GA), to transgenic 3xTg-AD mice for 8 weeks, then assessed their memory skills.

The mice that researchers used in the trial were 15-month-old females. These transgenic mice have three mutations associated with AD. They develop the characteristic plaque and tangle pathology of AD by around 12 months of age.

Researchers gave the trial mice subcutaneous injections of GA for 8 weeks. One control group received injections of phosphate-buffered saline (PBS). Wild-type mice made up two other control groups, one receiving GA, the other PBS.

“GA has been used for many years to treat MS. It appears to modify T cell responses, so the immune response is less aggressive, but we don’t really understand the mechanism,” said Dr. Michael O’Banion, M.D., Ph.D., professor of neuroscience, and senior author of the study.

“This is an interesting study exploring the use of a drug developed for another condition as a possible treatment for Alzheimer’s. The work done here by Dr. O’Banion and others is a promising first step.”

– Dr. Heather Snyder, Ph.D., vice president of medical and scientific relations at the Alzheimer’s Association

After 8 weeks, researchers assessed memory skills in the mice. They also analyzed their brain tissue to look for changes in the microglia, amyloid plaques, and tau tangles.

Improved memory

Researchers tested the memory skills of the mice using Novel Object Recognition (NOR). They first allowed the mice to investigate two objects in a box, then removed the mice from the box. The scientists left one object, the “familiar object,” inside the box and changed the other, the “novel object.”

They returned the mice to the box 2 hours later and scored them on how much time they spent exploring each object. The researchers saw a preference for the novel object as an indication of memory.

After 8 weeks, performance in NOR was markedly improved in the transgenic mice that the researchers had given GA compared with those on PBS. The performance of the GA-treated mice was comparable to the performance of the wild-type mice.

“Rodents are naturally curious. One interpretation is that [the GA-treated mice] have recovered a normal mouse behavior, which is to investigate a novel object,” Dr. O’Banion said.

Subtle changes

The study saw some changes in brain morphology, which might indicate why memory improved after GA treatment.

“In transgenic mice [with AD], the microglia show morphologies consistent with being more activated, responding to something that’s not right. In the GA mice, we saw subtle changes. The microglia were less activated,” Dr. O’Banion said.

“We also found modest changes in gene expression that suggested the GA was altering the immune activation,” he added. “A caveat is that if you improve the pathology, you should see less microglia activation — it’s an association, not a cause and effect.”

First steps

These findings in mice genetically engineered to have AD could be a step towards using GA as a treatment for the condition in people.

Dr. Verna R. Porter, M.D., a neurologist and director of programs for dementia, Alzheimer’s disease, and neurocognitive disorders at the Pacific Neuroscience Institute, an affiliate of Providence Saint John’s Health Center in Santa Monica, CA, commented: “This is a preliminary study in a murine [or] mouse model. This study does lend credence to the notion that therapies that effectively modulate the immune system could be effective in our fight against Alzheimer’s disease.”

This study replicated earlier work showing the benefits of GA in Alzheimer’s mouse models, but Dr. O’Banion urged caution in interpreting their findings: “It is important to recognize that there was an association of benefits in a cognitive test and Alzheimer’s pathological hallmarks. The question remains whether the glatiramer affecting microglia led to the improvement.”

“It’s going to take a lot more research to dig into the mechanism of why this might have a benefit.”

— Dr. O’Banion

Call for clinical trials

The researchers plan to conduct more mouse studies to see whether they can replicate these findings but would like the drug to go into clinical trials.

“Here we have a drug that has been used in people for over 15 years, so maybe it is something that should be tried in a clinical trial,” Dr. O’Banion said.

Dr. Snyder echoed this sentiment: “Since scientists are building on previous research, much is already known about the drug’s potential side effects. It may take less time for the drugs to be tested, and the clinical trials may be less expensive.”

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