No drug available today can prevent or slow the progression of Alzheimer’s disease, which afflicts an estimated 5.7 million people in the United States alone. A new type of treatment developed by researchers at the University of Florida provides a potential path to an effective treatment.
The study examines a modified version of a protein found on the surface of immune cells. When tested in mice, it reduced the buildup of amyloid plaques in the brain, a characteristic feature of Alzheimer’s disease. It also blocked the toxic effects of the peptides that form these plaques, preventing them from killing neurons. While the treatment is far from being available for people, researchers are optimistic that it could be safe and have fewer side-effects than pharmacological alternatives.
We spoke with Paramita Chakrabarty, a researcher at the University of Florida who co-led the study, to learn more.
ResearchGate: What treatments are currently available for Alzheimer’s disease?
Paramita Chakrabarty: There are multiple drugs that can allay the symptoms in Alzheimer’s disease patients but these do not treat the underlying cause of the disease or slow disease progression. There are no drugs that can cure or even delay the inexorable cognitive decline and neurodegeneration in these patients.
There are several ongoing clinical trials targeting some of the underlying pathologies in Alzheimer’s diseases, with the hope that these drugs can one day be used as treatments to stop, slow or prevent Alzheimer’s disease. These include immunotherapies against amyloid β and tau as well as inhibitors against enzymes that produce amyloid β.
RG: How does the treatment you identified in this study work?
Chakrabarty: Most scientists agree that inflammation in the brain can play a role in Alzheimer’s disease. Microglia and astrocytes, the immune cells of the brain, respond to the build-up of toxic proteins (amyloid β and tau) using specialized receptors called Toll-like receptors (TLR). Experiments done in animal models show these immune cells can help clear some of these pathologies when TLRs are stimulated. However, while doing so, these cells often secrete products that cause bystander damage, such as cell death. In our experiments, we created a version of the TLR that would recognize and bind to toxic amyloid β but would not stimulate the immune cells. We reasoned that this would clear amyloid β by scavenging these toxic molecules without causing bystander damage.
RG: How likely is it that this treatment could work for humans?
Chakrabarty: New drugs typically take years to advance from conceptualization to actual patient availability. As with other current drugs being used in clinical trials and preclinical testing, we are a long way from taking this immune biotherapy to the clinic. However, it is possible to envisage a concept of an immune biotherapy, such as this, in combination with other medications to have a successful disease modifying outcome in Alzheimer’s patients.
RG: Would it be safe?
Chakrabarty: Natural variants of TLRs, similar to our biologic therapy, have been discovered in mammals, including humans. This suggests that such a biotherapy may be potentially safe and preferable to use rather than pharmacologic interventions that can have potential unwanted side-effects. Such naturally-occurring decoy TLRs have been shown to have a role in limiting runaway inflammation and bystander toxicity in other experimental systems.
RG: What are the next steps?
Chakrabarty: The next steps for our research is to examine whether this decoy receptor can target and clear other types of proteinaceous aggregates linked to Alzheimer’s disease.
We would like to thank our partners and colleagues at the Mayo Clinic and Institute for Systems Biology and funding from the National Institutes of Health that supports grants under the AMP-AD consortium, the 1Florida Alzheimer’s Disease Research Center and from the BrightFocus Foundation.