Health
Analysis shows new therapeutic goals for the disease-ScienceDaily
Although new treatments for Alzheimer’s disease are urgently needed, many clinical trials of investigational drugs have failed to create promising options. Currently, a team at Massachusetts General Hospital (MGH) and Harvard Medical School (HMS) has developed an artificial intelligence-based method for screening currently available medications for possible treatments for Alzheimer’s disease. This method may represent a fast and inexpensive way to reuse existing therapies for new treatments for this progressive debilitating neurodegenerative condition. Importantly, it may also help uncover new unexplored targets for treatment by pointing out the mechanism of drug action.
“Diverting FDA-approved drugs for Alzheimer’s disease is a fascinating idea that can help accelerate the arrival of effective treatments, but unfortunately, even previously approved drugs Clinical trials require significant resources and it is not possible to evaluate all drugs in patients with Alzheimer’s disease. Diseases, “said Dr. Artem Sokolov, director of informatics and modeling at the HMS Institute for Systems Pharmacology. Explains. “Therefore, we have built a framework for prioritizing drugs and helped clinical research focus on the most promising ones.”
In the article published in Nature Communications, Sokolov and his colleagues describe a framework called DRIAD (Drug Repurposed In Alzheimer’s Disease) that relies on machine learning. This is an area of artificial intelligence where systems are “trained” with vast amounts of data and “learned” to identify telltales. Create patterns to enhance the decision-making of researchers and clinicians.
DRIAD works by measuring what happens to human brain nerve cells when treated with drugs. This method then determines whether drug-induced changes correlate with molecular markers of disease severity.
This approach also allowed researchers to identify drugs that had protective and damaging effects on brain cells.
“It also helps to estimate the direction of such correlations and identify and rule out neurotoxic drugs that accelerate rather than prevent neuronal cell death,” said a researcher at MGH’s Department of Neurology. Dr. Steve Rodriguez, co-lead author and instructor, said. With HMS.
With DRIAD, researchers can find out which proteins are the targets of the most promising drugs. If there is a common tendency for targets, the approach was designed by Dr. Clements Hug, a researcher and co-lead author at the Institute of Systems Pharmacology.
The team applied screening methods to 80 FDA-approved and clinically tested drugs under a variety of conditions. The analysis provides a ranked list of candidates, and several anti-inflammatory drugs used to treat rheumatoid arthritis and hematological malignancies have emerged as potential candidates. These drugs belong to a class of drugs known as Janus kinase inhibitors. These drugs work by blocking the action of the Janus kinase protein, which is suspected to play a role in Alzheimer’s disease and is known for its role in autoimmune conditions, which promotes inflammation. The team’s analysis also pointed to other potential therapeutic goals for further investigation.
“We are pleased to share these results with the academic and pharmaceutical research communities, and we hope that further validation by other researchers will improve the priority of these drugs in clinical research,” Frank Wilkins said. Jr. Mark Albers, MD, said. He is a family-donated scholar, deputy director of the MGH Massachusetts Alzheimer’s Center for Therapeutic Science, and a faculty member of the HMS Institute for Systems Pharmacology. One of these drugs, baricitinib, was investigated by Alberth in clinical trials in patients with subjective cognitive impairment, mild cognitive impairment, and Alzheimer’s disease, and was investigated by MGH in Boston and Holy Cross in Fort Lauderdale, Florida. It will be released soon in Health. “In addition, independent validation of designated drug discovery targets may provide new insights into the mechanisms behind Alzheimer’s disease and lead to new therapies,” says Albers.
This work was supported by the National Institute on Aging, the CART Foundation, and the Harvard University Catalytic Program for Capacity Development and Diversity Inclusion.
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