Scientists examine a potential drug to improve memory in people with Alzheimer’s disease. yacobchuk/Getty Images A small clinical trial suggests that a drug that stimulates the innate immune system might improve the memory of individuals with mild or moderate Alzheimer’s disease.
A 3-week course of injections of the drug, which is a natural protein, also led to improvements in markers of the condition in the participants’ bloodstreams.
A larger clinical trial, which will treat the condition in more people over a longer period of time, is already underway.
Alzheimer’s disease is a brain condition in which an individual’s memory and thinking skills progressively decline.
In the United States, more than 5.5 million people may have this condition, most of whom are over the age of 65 years.
Scientists know that immune-driven inflammation plays a prominent role in Alzheimer’s progression. However, a new study adds to the evidence that the immune system may also help repair some of the nerve damage that is associated with the condition.
A small clinical trial found that stimulating the production of certain immune cells and signaling molecules can boost memory and improve some markers of the condition in people’s blood.
The immune cells and molecules in question are part of the innate immune system , which is the first line of defense against pathogens.
The study now appears in the journal Translational Research & Clinical Interventions .
Around 2 decades ago, researchers noticed that people with the autoimmune condition rheumatoid arthritis were 40–50% less likely to develop Alzheimer’s disease.
At first, they attributed this protective effect to the drugs that people with rheumatoid arthritis take to ease the painful inflammation in their joints.
However, subsequent clinical trials of nonsteroidal anti-inflammatory drugs (NSAIDs) in people with Alzheimer’s or mild cognitive impairment did not show any benefits.
Dr. Huntington Potter, Ph.D., and colleagues at the University of Colorado Alzheimer’s and Cognition Center in Aurora wondered if there was something about the condition itself that shields people with rheumatoid arthritis from Alzheimer’s.
People with rheumatoid arthritis have raised levels of a protein called granulocyte-macrophage colony-stimulating factor (GM-CSF) in their blood. Conversely, a recent study found that people with Alzheimer’s have reduced levels of GM-CSF in their cerebrospinal fluid.
“Thus, naturally increased levels of GM-CSF in people with rheumatoid arthritis may be one reason that they are protected from Alzheimer’s disease,” says Dr. Potter.
Doctors prescribe a genetically engineered form of GM-CSF known as sargramostim to accelerate the regeneration of white blood cells following chemotherapy for cancer or a bone marrow transplant.
GM-CSF stimulates bone marrow to produce two types of white blood cell: macrophages and granulocytes. These are part of the body’s innate immune defenses.
The protein promotes inflammation, but it also protects nerve cells after injury and spurs the growth of new nerves.
In laboratory-based research , Dr. Potter and team found that GM-CSF reversed cognitive impairment and restored spatial memory in a mouse model of Alzheimer’s.
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For their clinical trial, they recruited 40 people with mild or moderate Alzheimer’s and randomly assigned them to receive a 3-week course of either sargramostim injections or saline injections (the placebo control).
By the end of the treatment, those who received sargramostim performed significantly better on a standard test of memory known as the mini mental state examination .
There were also improvements in biomarkers of Alzheimer’s in their blood, which suggests that sargramostim had alleviated some of the characteristic features of the condition in their brains.
These features include the accumulation of beta-amyloid plaques, tangles of a protein called tau, and neurodegeneration. “These results suggest that short-term sargramostim treatment leads to innate immune system activation, cognition and memory improvement, and partial normalization of blood measures of amyloid and tau pathology and neuronal damage in participants with mild-to-moderate Alzheimer’s disease.”
– Dr. Huntington Potter Importantly, the treatment also appeared to be safe, and the participants tolerated it well.
Indeed, the primary purpose of the study was to assess safety. The small sample size and short duration of treatment meant that it lacked the statistical power to gauge possible improvements in cognition other than memory.However, the team has now started a larger clinical trial with more participants and a longer treatment period.