Research Roundup: AI Helps ID Alzheimer’s Treatments and More

BioSpace

 

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.

AI Helps Identify Possible Alzheimer’s Treatments

Researchers at Massachusetts General Hospital developed an artificial intelligence (AI) that quickly identifies drugs currently available that might treat Alzheimer’s disease. It also can point to potential new drug targets. The framework is called Drug Repurposing In Alzheimer’s Disease (DRIAD), and depends upon machine learning, where systems are trained on huge amounts of data to learn to identify patterns. They published their research in Nature Communications.

“Repurposing FDA-approved drugs for Alzheimer’s disease is an attractive idea that can help accelerate the arrival of effective treatment—but unfortunately, even for previously approved drugs, clinical trials require substantial resources, making it impossible to evaluate every drug in patients with Alzheimer’s disease,” said Artem Sokolov, director of Informatics and Modeling at the Laboratory of Systems Pharmacology at Harvard Medical School (HMS). “We therefore built a framework for prioritizing drugs, helping clinical studies to focus on the most promising ones.”

DRIAD measures what happens to human brain neural cells when treated with a drug. The AI determined if the changes caused by the drug are associated with molecular markers of disease severity. It can also examine which proteins are targeted by the most promising molecules and determine common trends among the targets. The researchers applied the AI to 80 FDA-approved and clinically tested drugs across a broad range of indications. The AI came up with a ranked list of candidates, with the top spots anti-inflammatory drugs used to treat rheumatoid arthritis and blood cancers. They all are JAK inhibitors (Janus kinase inhibitors), which block the action of inflammation-driving Janus kinase proteins, which are known to be associated with autoimmune disease, and are suspected of playing a role in Alzheimer’s.

Biomarkers Associated with Severe Forms of COVID-19

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Researchers from the University of Montreal Hospital Research Centre (CRCHUM) identified new biomarkers that are linked to the severity of COVID-19. They noted that a group of immune changes are specifically linked to SARS-CoV-2 virus, as well as to its severity, its 30-day evolution and 60-day mortality. They used a blood test to screen 50 patients with COVID-19 and compared them to those of 22 patients with similar gender and age that were hospitalized for other acute diseases, and those of 49 healthy controls. They identified subsets of dysregulated immune cells specific to the COVID-19 patients, and some of those immune changes were associated with patients on ventilators and at greatest risk of death. They also confirmed what other studies have suggested, that disturbances in the immune system like neutrophilia or lymphopenia are associated to the severity of the disease in hospitalized patients, but are not necessarily specific to COVID-19.

Astronauts Infected Human Cells with Salmonella

Scientists at Arizona State University designed a study aboard Space Shuttle mission STS-131, where human intestinal epithelial cells were cultured, and a subset of the cultures was infected with either Salmonella typhimurium or were controls. Their research demonstrated how the microgravity environment in spaceflight changed the molecular profile of human intestinal cells and how those expression patterns changed even more in response to infection. One of the bottom-line findings was that spaceflight and the microgravity environment increases the potential of infectious disease.

High Doses of CBD May Improve Cognition in Familial Alzheimer’s

A study out of the Medical College of Georgia at Augusta University found that a two-week treatment of high doses of CBD restored the function of two proteins that appeared to decrease the accumulation of beta-amyloid plaque, a key component of Alzheimer’s disease. In this experimental model of early onset familial Alzheimer’s, the treatment appeared to improve cognition. The proteins TREM2 and IL-33 help the brain’s immune cells to consume dead cells and other debris such as the beta-amyloid plaque that builds up in Alzheimer’s brains. The study suggested that CBD normalizes levels and functions, improving cognition as it decreased levels of the immune protein IL-6, which is linked to high inflammation levels in Alzheimer’s. CBD appears to normalize IL-33 levels. IL-33 is a protein whose highest expression in humans is typically in the brain. Its job is to alert the immune system that there is an invader, such as beta-amyloid. CBD also improved expression of TREM2, which is expressed on microglial cells, immune cells only found in the brain. The research was conducted on mice models, and the CBD was placed in the belly of the mice. They are working on both animal and human inhalers.

New Organelle Associated with Cancer Metastasis

Although it doesn’t yet have a name, researchers at Princeton University discovered a previously unknown organelle that plays a role in bone metastasis. It is created by way of a liquid-liquid phase separation, when liquid “blobs” of living materials merge. The team was investigating metastasis and weren’t specifically looking at liquid-liquid phase separations, and believe it is the first time the phenomenon has been implicated in cancer metastasis. They described it as the “merging blobs turned out to create more than the sum of their parts, self-assembling into a previously unknown organelle.” The organelle is associated with the Wnt signaling pathway, which plays several roles in healthy bone growth as well as in cancer metastasizing to bones. They were studying the interplay between Wnt, a signaling molecule called TGF-b, and the DACT1 gene when they discovered the new organelle. Bone tumors initially induce Wnt signaling. Then TGF-b, common in bones, suppresses Wnt signaling. Then tumors then stimulate the growth of osteoclasts, which clean away old bone tissue. This decreases the TGF-b concentrating, stimulating even more DACT1 hoarding and subsequent Wnt suppression.

Study Suggests UK, South African and Brazilian COVID-19 Variants Can Evade Antibodies

Investigators at Washington University School of Medicine in St. Louis conducted laboratory studies that suggest that the COVID-19 variants from South Africa, the UK and Brazil might be able to evade antibodies created by vaccines or natural infections. All the variants carry multiple mutations in their spike genes, which appear to decrease the effectiveness of spike-targeted drugs and vaccines. To date, it does not appear that the new variants completely evade the antibodies, but the vaccines, therapeutic antibodies and convalescent antibodies may be less effective on these variants.

“We don’t exactly know what the consequences of these new variants are going to be yet,” said Michael S. Diamond, the Herbert S. Gasser Professor of Medicine at WU School of Medicine. “Antibodies are not the only measure of protection; other elements of the immune system may be able to compensate for increased resistance to antibodies. That’s going to be determined over time, epidemiologically, as we see what happens as these variants spread. Will we see reinfections? Will we see vaccines lose efficacy and drug resistance emerge? I hope not. But it’s clear that we will need to continually screen antibodies to make sure they’re still working as new variants arise and spread and potentially adjust our vaccine and antibody-treatment strategies.”

 

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