Research Roundup: Gum Disease and Alzheimer’s, a Cancer Vaccine, Cold Plasma and More
There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.
Bacteria Associated With Gum Disease Linked to Alzheimer’s
A bacterium associated with gum disease, Porphyromonas gingivalis, has been found to travel through the body and emit toxins associated with Alzheimer’s disease, rheumatoid arthritis and aspiration pneumonia. Researchers at the University of Louisville School of Dentistry and Jagiellonian University in Krakow, Poland, presented their findings at the American Association of Anatomists annual meeting.
“Oral hygiene is very important throughout our life, not only for having a beautiful smile but also to decrease the risk of many serious diseases,” stated Jan Potempa, professor at U of L School of Dentistry and head of the department of microbiology at Jagiellonian University. “People with genetic risk factors that make them susceptible to rheumatoid arthritis or Alzheimer’s disease should be extremely concerned with preventing gum disease.”
The presence of P. gingivalis in Alzheimer’s patients’ brains has been observed before. Potempa’s group, in collaboration with Cortexyme, compared brain samples from deceased people with and without Alzheimer’s who were about the same age at the time of death. In the samples from Alzheimer’s patients, they found that P. gingivalis was more common, as well as the presence of its primary toxins, known as gingipains. An experimental drug that blocks gingipains, COR388, is presently in Phase I clinical trials for Alzheimer’s disease.
Immune Cells to Predict Cancer Outcomes
Researchers at the University of Edinburgh identified key changes in immune cells associated with tumors. They also found 37 genes that were highly expressed in breast cancer tumor immune cells, known as tumor-associated macrophages (TAMs). The researchers published their work in the journal Cancer Cell.
“These studies are the culmination of eight years’ of experiments and show convincingly that tumor-infiltrating immune cells are vital to understanding cancer spread,” stated Jeff Pollard, Director of the Medical Research Council Centre for Reproductive Health at the University of Edinburgh, who led the study. “Tumor macrophages and monocytes show promise as markers for cancers and may help doctors make a prognosis, as well as opening routes to drug discovery.”
They studied the role of immune cells in the womb lining, or endometrium, and in breast cancers. They found that the white blood cells, monocytes, present in the blood of patients with these types of cancers were different than those in healthy individuals. The genetic signature was particularly strong in aggressive cancers, including triple negative breast cancer. They also identified specific genes that might be targeted with future drugs, specifically the SIGLEC1 and CCL8 genes.
Cancer Vaccine Shows Promise in Early Trial
Researchers with the Icahn School of Medicine at Mount Sinai in New York have had promising results with a cancer vaccine in an early-stage clinical trial. They published their work in the journal Nature Medicine.
Indolent non-Hodgkin’s lymphomas (iNHLs) do not respond to standard cancer therapy and respond poorly to checkpoint inhibitors. The research group, led by Joshua Brody, Director of the Lymphoma Immunotherapy Program at Icahn, showed that lymphoma cells could directly prime T-cells, but that actual immunity required multiple exposures or cross-presentation.
Brody and his team developed a therapy that combined Flt3L, radiotherapy, and a TLR3 agonist, “which recruited, antigen-loaded and activated intratumoral, cross-presenting dendritic cells (DCs),” the authors wrote.
Brody told Live Science, “We’re seeing tumors all throughout the body melting away,” after injecting a single tumor.
The vaccine was tested in 11 patients with NHL. Not all patients responded to the therapy. But some of the patients, three, went into remission for relatively long periods. Because of its promise, the vaccine is now being tested in breast and head-and-neck cancers. The vaccine also appears to increase the effectiveness of checkpoint inhibitors in the disease, what Brody told Live Science “are remarkably synergistic.”
Cold Plasma Kills Almost All Airborne Viruses
Researchers at the University of Michigan have shown that dangerous airborne viruses can be killed “on-the-fly” when exposed to so-called “cold plasma,” or energetic, charged air molecule fragments. They published their work in the Journal of Physics D: Applied Physics.
“The most difficult disease transmission route to guard against is airborne because we have relatively little to protect us when we breathe,” stated Herek Clack, UM research associate professor of civil and environmental engineering.
The researchers evaluated the virus-killing speed and effectiveness of nonthermal plasma, that ionized particles created around electrical discharges, such as sparks. They found the reactor inactivated or removed 99.9% of a test virus, mostly because of inactivation. The reactor had borosilicate glass beads packed into a cylinder. They initiated sparks between the void spaces and passed a model virus via flowing air into the reactor.
The work would seem to have more immediate implications for livestock farmers, who often use air filtration systems to help mitigate the risk of the spread of avian and porcine viruses.
“Allelic Drive” Leads to Even More Precise CRISPR Gene Editing
Since the discovery of CRISPR not so long ago, scientists are consistently finding ways to make it better. Researchers at the University of California, San Diego (UCSD) recently developed a “gene drive” or “allelic drive” that works with a guide RNA to direct CRISPR to cut undesired gene variants and replace it with a preferred version. They published their research in the journal Nature Communications.
The researchers use a word-processing analogy to describe it, saying that typical CRISPR allows scientists to edit sentences of genetic data, but this new allelic drive allows letter-by-letter editing. “If we incorporate such a normalizing gRNA on a gene-drive element, for example, one designed to immunize mosquitoes against malaria, the resulting allelic gene drive will spread through a population,” stated Ethan Bier, the study’s senior author. “When this dual action drive encounters an insecticide-resistant allele, it will cut and repair it using the wild-type susceptible allele. The result being that nearly all emerging progeny will be sensitive to insecticides as well as refractory to malaria transmission.”
They developed two versions of the allelic drive, one that utilizes “copy-cutting,” where using CRISPR, they cut the undesired gene, and “copy-grafting” that promotes transmission of a favored allele next to the site that is selectively protected from gNRA cleavage.
New Drug-Screening Method to ID Oncology Combination Therapies
Scientists with the University of California, San Francisco (UCSF) developed a large-scale screening method that can identify drugs that work in combinations against cancer effectively but aren’t particularly effective on their own. They followed up by identifying a combination of such drugs and tested them in blood cancer and some solid tumor cells. They published their work in the journal Cell Reports.
“Many cancers either fail to respond to a single targeted therapy or acquire resistance after initially responding,” stated Jeroen Roose, professor of anatomy and senior author of the paper. “The notion that combining targeted therapies is a far more effective way to treat cancer than a single-drug approach has long existed. We wanted to perform screens with saturating coverage to understand exactly what combinations should be explored.”
They focused on a drug that targets PI3K, an enzyme that promotes tumor growth, including in T-cell acute lymphoblastic leukemia (T-ALL). Current PI3K inhibitors slow cancer growth, but don’t typically kill cancer cells. The research team was looking for something that could be used with a PI3K inhibitor that would kill the cancer cells.
They decided RNA interference (RNAi) would be the way to go, which can reduce the activity of specific genes. In short, their screening process involved growing two different human T-ALL cell lines exposed to PI3K inhibitors, while simultaneously administering shRNAs to determine which genes, when silenced from exposure to the drugs, actually killed the cancer. From that point, they then focused on 10 gene targets that would likely kill T-ALL cancer cells in combination with PI3K drugs. Once they tested them, they found that nine of the combination therapies could kill T-ALL. They further evaluated drug combinations on mouse models of T-ALL and found that the most effective combination extended survival by 150 percent.