Research Roundup: Alzheimer’s Protective Gene and More

 

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

A Gene That Protects Against Alzheimer’s Disease

Researchers with Queen Mary University of London discovered a gene that naturally suppresses the signs of Alzheimer’s disease in human brain cells. They have also developed a rapid drug-screening system for treatment that might delay or prevent the disease. The researchers collected hair cells from people with Down syndrome (DS), who have about a 70% chance of developing Alzheimer’s in their lifetime. They reprogrammed them to become stem cells, which were then stimulated to become brain cells in a Petri dish. In the brain-like cells, they identified Alzheimer’s-like pathology. They found this could be used as an early preventative-drug testing platform. They published their research in the journal Molecular Psychiatry.

They then tested two different drugs known to inhibit beta-amyloid production, a hallmark of the disease, and tested them on the cultures. Within six weeks they appeared to prevent the Alzheimer’s-like pathology. The drugs themselves had already failed clinical trials, but they used them as proof-of-concept studies to show it could be used as a screening system. They also identified a naturally functioning Alzheimer’s suppressor gene (BACE2) that behaves like tumor suppressor genes in cancer.

“Although it’s still early days, the system raises a theoretical possibility for further development as a tool to predict who might develop Alzheimer’s,” said Dean Nizetic, lead researcher from Queen Mary University of London. “The same stem cell process could be used on anyone’s hair follicles, the resulting brain cells of which may or may not then develop Alzheimer’s-pathology in the dish. The idea would be to catch the people at higher risk of early disease in a cell-based system, before it starts in a person’s brain, and allow for the possibilities of individualized preventive interventions. We are still a long way from reaching this point.”

Common Antibody Element in Best Response to COVID-19 Virus

Scientists with the The Scripps Research Institute, analyzing various human antibodies that appear to neutralize SARS-CoV-2, the virus that causes COVID-19, found a common molecule in them. They reviewed data from almost 300 anti-COVID-19 antibodies that their laboratories and others have identified in convalescent COVID-19 patients in the last few months. A subset of them were especially effective at neutralizing the virus. And what they had in common was a gene, IGHV3-53. Previous research suggested that antibodies encoded by IGHV3-53 are typically present, sometimes in small numbers, in the blood of healthy people. The gene encoded for about 10% of the 294 antibodies analyzed, and they found that these antibodies contained an unusually short variation of the CDR H3 loop, which is normally a key target-binding element. Nonetheless, they are very potent against SARS-CoV-2 compared to other antibodies that are not encoded by that specific gene. The researchers believe this will provide not only a better understanding of the virus and how antibodies attack them but could guide future vaccine development.

A Cancer Vaccine to Activate the Immune System Against Broad Range of Cancers

Scientists with the Translational Research Institute developed a new vaccine in collaboration with The University of Queensland that appears to activate the immune system against numerous cancers, including leukemia, breast cancer, lung cancer and pancreatic cancers. The vaccine is made up of human antibodies fused with tumor-specific protein. The advantage of this approach over existing cancer vaccines is it can be produced “off the shelf” and the prototype targets the key tumor cells required for initiation of tumor-specific immune responses, which should maximize their potential effectiveness.

Finding the Fountain of Youth

Investigators at the University of Southern California found that the drug mifepristone can extend the lives of two different species in laboratory studies—the fruit fly and roundworms. The drug, also known as RU-486, is used to end early pregnancies and to treat cancer and Cushing disease. The drug appears to affect certain metabolic pathways that involve a juvenile hormone. The researchers believe there may be similar results in humans, although a better understanding of how the drug actually extends lifespan in fruit flies and roundworms would be necessary.

Gene IDed that is Responsible for Glioblastoma Brain Cancer

Researchers at the University of Virginia Health System identified an oncogene that is responsible for glioblastoma, the deadliest form of brain cancer. The gene, AVIL, typically helps cells maintain their size and shape. But under certain conditions, it can shift into overdrive, which causes cancer cells to grow and metastasize. In laboratory mice, they blocked the gene’s activity, which destroyed the glioblastoma cells but did not affect healthy cells. They found that AVIL is overexpressed in 100% of glioblastoma cells and clinical samples but is hardly expressed in normal cells and tissues.

New Technique Could Make CRISPR Even Better

CRISPR gene editing is a biological revolution, but researchers keep finding ways to improve on it. Investigators at Cornell University identified a protein called AcrVIA1, which is found in Listeria bacteria in soil, that can halt the CRISPR-Cas13 editing process. This can be useful in controlling CRISPR-Cas13 editing and has the potential to be applicable to COVID-19 research, because CRISPR-Cas13 can be used to edit RNA and SARS-CoV-2 is an RNA virus.

Large Study Used Umbilical Cord Blood to Successfully Treat Rare Genetic Disorders

Scientists at UPMC Children’s Hospital of Pittsburgh used umbilical cord blood to safely and effectively treat 44 children born with a number of non-cancerous genetic disorders, including sickle cell, thalassemia, Hunter syndrome, Krabbe disease, metachromatic leukodystrophy (MLD) and other immune deficiencies. The goal was to develop a somewhat universal treatment. The research was published in Blood Advances.

“There has been a lot of emphasis placed on cool new technologies that might address these diseases, but—even if they prove effective—those aren’t available to most centers,” said Paul Szabolcs, senior author and division director of bone marrow transplantation and cellular therapies at UPMC Children’s. “The regimen we developed is more robust, readily applicable and will remain significantly less expensive.”