January 25 Research Roundup: Alzheimer’s Memory Recovery and Testing, New Antibiotics, Possible Stem Cell Therapy for Diabetes and More
There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.
It Might Be Possible to Restore Memory Function in Alzheimer’s Disease
A team of researchers at the University at Buffalo published a possible approach to reverse memory loss in Alzheimer’s disease. The study was published in the journal Brain. The work focuses on epigenetic changes in animal models of Alzheimer’s.
“In this paper, we have not only identified the epigenetic factors that contribute to the memory loss, we also found ways to temporarily reverse them in an animal model of AD,” stated senior author Zhen Yan, a SUNY Distinguished Professor in the Department of Physiology and Biophysics in the Jacobs School of Medicine and Biomedical Sciences at UB.
The mice carried a gene mutation for familial AD and work was also conducted on post-mortem brain tissues from AD patients. The disease, they indicate, comes from genetic and environmental risk factors—the primary environmental risk factor being aging. Those combine to create gene expression changes, but not much is known about those changes. The epigenetic changes in the disease mostly occur in the later stages, where patients can’t retain recent information and show the greatest levels of cognitive decline. They found that a key reason for the decline is the loss of glutamate receptors, which are vital to learning and short-term memory.
“We found that in Alzheimer’s disease, many subunits of glutamate receptors in the frontal cortex are downregulated, disrupting the excitatory signals, which impairs working memory,” Yan stated.
The research found that the loss of glutamate receptors is caused by an epigenetic process called repressive histone modification, which is increased in AD. They then injected the animals with chemicals that inhibit the enzyme that controls repressive histone modification. It resulted in rescue of cognitive function. The improvements lasted about a week. Future work will focus on compounds that are better at penetrating the brain and last longer.
How and Why CMV Gets Reactivated as a Life-Threatening Infection
Cytomegalovirus (CMV) is a common virus, and generally not a problem for healthy individuals. But in people with a compromised immune system, the virus can become life-threatening. Researchers with the Fred Hutchinson Cancer Research Center published research in the journal Science describing the roles different immune cells play in this reactivation.
“This is a big deal for the bone marrow transplantation field,” stated Geoffrey Hill, the paper’s senior co-author and director of Hematopoietic Stem Cell Transplantation at Fred Hutchinson. “Our study shows for the first time that antibodies can play a dominant role in controlling CMV reactivation. This is turning dogma on its head.”
CMV infection is the most common complication of bone marrow transplantation. The team found, that instead of T-cells, B-cells played a critical role in controlling CMV.
Possible New Antibiotic for C. diff Infections
Clostridium difficile infections (C. diff or CDI) are potentially fatal and are common in individuals who have had antibiotics over an extended period of time. They are particularly common in aging populations. Researchers at Flinders University in Australia are working with a new antibiotic called Ramizol that seems to be effective against antibiotic-resistant strains of C. diff. The research was published in the journal Scientific Reports.
Ramizol is a first-in-class stryrylbenzene-based antibiotic indicated for CDI. Researchers at Flinders and Boulos & Cooper Pharmaceuticals investigated the antibiotic in hamsters. Ramiz Boulos, adjunct research associate at Flinders and chief executive officer of Boulos & Cooper, stated, “Cases of CDI disease are rising and the strains are becoming more lethal. If there is an imbalance in your intestines it can begin to grow and release toxins that attack the lining of the intestines which leads to symptoms.”
Hamsters with CDI were dosed with Ramizol, a significant group of the hamsters survived the lethal infection. And in repeated exposure to the antibiotic, no rodents experienced serious side effects or changes in weight.
“Our research indicates Ramizol is an extremely well-tolerated antibiotic in rats, with good microbiology and antioxidant properties,” Boulos stated. “It also has high chemical stability and is scalable because of the low cost of manufacturing, which could make it a viable treatment option.”
Possible Breakthrough in Using Stem Cells to Treat Diabetes
Researchers with Washington University School of Medicine in St. Louis published research in the journal Stem Cell Reports, describing how they transplanted insulin-secreting beta cells they developed from human stem cells into mice. Within a few days, the beta cells began creating insulin and continued to control blood sugar in the rodents for months.
“We’ve been able to overcome a major weakness in the way these cells previously had been developed,” stated principal investigator Jeffrey R. Millman. “The new insulin-producing cells react more quickly and appropriately when they encounter glucose. The cells behave much more like beta cells in people who don’t have diabetes.”
Earlier work had beta cells secreting insulin in response to glucose, but it was, Millman said, “more like fire hydrants, either making a lot of insulin or none at all. The new cells are more sensitive and secrete insulin that better corresponds to the glucose levels.”
New Biomarker for Alzheimer’s Disease Identified
Scientists at the German Center for Neurodegenerative Diseases (DZNE), the Hertie Institute for Clinical Brain Research (HIH) and the University Hospital Tuebingen identified a protein in blood that can precisely track Alzheimer’s disease progression before the first symptoms appear. The research was published in the journal Nature Medicine.
The protein is neurofilament light chain (NfL). When brain cells die, the debris left can be detected in the blood. “Normally, however, such proteins are rapidly degraded in the blood and are therefore not very suitable as markers for a neurodegenerative disease,” stated Mathias Jucker, senior researcher at the DZNE and the HIH. “An exception, however, is a small piece of so-called neurofilament that is surprisingly resistant to this degradation.”
The test Jucker and his team developed is based on the NfL filament. NfL accumulates in the blood way ahead of clinical symptoms and appears to be correlated to the progression of the disease. The group monitored NfL concentration in the individuals year after year. They found that up to 16 years before the onset of dementia symptoms, there were changes observed in their blood. “It is not the absolute neurofilament concentration, but its temporal evolution, which is meaningful and allows predictions about the future progression of the disease,” Jucker stated. “We were able to predict loss of brain mass and cognitive changes that actually occurred two years later.”
Stimulating Immune Cells to Eat Cancer
Researchers with the University of Pennsylvania School of Medicine have found a way to fuel macrophages in a way that fuels them to attack and eat cancer cells. The research was published in the journal Nature Immunology.
“It turns out macrophages need to be primed before they can go to work, which explains why solid tumors may resist treatment with CD47 inhibitors alone,” stated the study’s senior author, Gregory L. Beatty.
The group activated macrophages with CpG, a toll-like receptor agonist, finding that it quickly induced tumor shrinkage and prolonged the survival of mice without requiring T-cells. They essentially required macrophage metabolism, which allowed CpG to be effective.
“Cancer does not shrink without the help of macrophages and macrophages need the right fuel to eat cancer cells and shrink tumors,” stated Jason Mingen Liu, an MD and PhD graduate student in Beatty’s lab, and the study’s lead author. “To do this, a shift in metabolism is needed to steer the energy in the right direction. It is the metabolism that ultimately allows macrophages to override signals telling them not to do their job.”