- A medicine doctors use to treat multiple sclerosis may be beneficial in treating Alzheimer’s symptoms, including memory loss.
- In mice, memory improved after 8 weeks of therapy with the medication.
The treated animals also demonstrated a decrease in amyloid plaques. - Clinical trials are needed to prove if the drug, glatiramer acetate, can halt the onset 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 range in the United Kingdom. Memory loss is one of the most troublesome symptoms of AD. A research published in Frontiers in Neuroscience has discovered that a medicine used to treat multiple sclerosis (MS) may help ease this discomfort.
Researchers from the Del Monte Institute for Neuroscience at the University of Rochester, NY, carried out the investigation in mice. The scientists gave the medication, glatiramer acetate (GA, to transgenic 3xTg-AD mice for 8 weeks, then examined their memory skills.
The mice that researchers utilized in the study were 15-month-old females. These transgenic mice exhibit three mutations linked with AD. They acquire the characteristic plaque and tangle pathology of AD by roughly 12 months of age.
Researchers gave the experimental mice subcutaneous doses of GA for 8 weeks. One control group got injections of phosphate-buffered saline (PBS) (PBS). Wild-type mice made up two other control groups, one getting GA, the other PBS.
“GA has been used for many years to treat MS. It appears to modulate T cell responses, so the immune response is less aggressive, but we don’t fully understand the mechanism,” said Dr. Michael O’Banion, M.D., Ph.D., professor of neurology, 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 tested memory skills in the mice. They also studied their brain tissue to search for alterations in the microglia, amyloid plaques, and tau tangles.
Improved memory
Researchers examined the memory capacities of the mice using Novel Object Recognition (NOR). They initially let the mice to study two things in a box, then withdrew the mice from the box. The scientists left one object, the “familiar object,” inside the box and altered the other, the “novel thing.”
They brought the mice to the box 2 hours later and rated them on how much time they spent examining each thing. The researchers perceived a preference for the unfamiliar object as an evidence of memory.
After 8 weeks, performance in NOR was considerably enhanced in the transgenic mice that the researchers had given GA compared with those on PBS. The performance of the GA-treated mice was equivalent to the performance of the wild-type mice.
“Rodents are inherently curious. One view is that [the GA-treated mice] have restored a typical mouse behavior, which is to examine a novel object,” Dr. O’Banion added.
Subtle modifications
The research detected some changes in brain shape, which could reflect why memory improved following GA therapy.
“In transgenic mice [with AD], the microglia display morphologies consistent with being more active, reacting to something that’s not right. In the GA mice, we noticed minor differences. The microglia were less activated,” Dr. O’Banion remarked.
“We also discovered small changes in gene expression that showed the GA was modifying the immunological activation,” he said. “A caveat is that if you ameliorate the pathology, you should observe less microglia activation – it’s a connection, not a cause and effect.”
First steps
These discoveries in mice genetically altered to have AD might be a step towards utilizing GA as a therapy 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 data does lend support to the hypothesis that medicines that successfully control the immune system might be beneficial in our battle against Alzheimer’s disease.”
This study repeated past work showing the advantages of GA in Alzheimer’s mice models, but Dr. O’Banion recommended caution in interpreting their findings: “It is crucial to understand that there was a connection between improvements in a cognitive test and Alzheimer’s pathology markers. The issue remains whether the glatiramer impacting 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 aim to do further mice tests to determine whether they can duplicate these findings but would like the medicine to proceed 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 reiterated this sentiment: “Since scientists are building on earlier studies, much is already known about the drug’s possible negative effects. It may take less time for the treatments to be examined, and the clinical trials may be less expensive.”
