December 7 Research Roundup: Genes for Dementia, Genes for Obesity, Genes for Tissue Regeneration and More

Test Tubes in a row with pipette putting pink liquid in them

There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.

Running Marathons Can Increase the Strain on your Heart

Although running marathons—26.2 miles—requires overall good cardiovascular fitness, a recent study by researchers at Camilo Jose Cela University in Madrid, Spain, published research in Circulation, Journal of the American Heart Association, citing increased cardiac strain biomarkers found in amateurs who run marathons.

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The study notes that the incidence of cardiac arrests in marathoners is about 1 in 50,000, which averages about 3 percent. However, the strain on the heart muscle, as measured by the biomarker levels of troponin I and troponin T in 63 runners was much higher after a full marathon. It went on to point out that a high proportion of all exercise-induced cardiac vents occur during marathons, especially in men 35 years of age and older.

“We typically assume that marathon runners are healthy individuals, without risk factors that might predispose them to a cardiac event during or after a race,” stated Juan Del Coso, lead investigator of the study. “But with the growing popularity of long-endurance races, the exponential increase in the number of participants, and the lack of appropriate training in some cohorts of amateur runners, our findings suggest that running shorter endurance races might reduce the strain imposed on the myocardium during running competition.”

2 Gene Groups Linked to Dementias

Researchers with the University of California, Los Angeles (UCLA) Health Sciences have identified two major groups of genes that, when mutated, results in overproduction of the tau protein, at least in mice. They published their research in the journal Nature Medicine.

The research was primarily conducted on mouse models of dementia. The UCLA team identified MAPT and GRN genes, which when mutated in three different species of mice showed signs of dementia. Their focus, however, was on frontotemporal dementia, which is a type of early-onset dementia. The processes involved are similar to those observed in Alzheimer’s disease and another type of dementia called supranuclear palsy.

They then searched a database of the genetic effects of experimental drugs to try to find ones that might affect the loss of neurons.

“Our study is the most comprehensive published effort to date to identify the source of neurodegeneration across species and provides an important roadmap for the development of potentially effective new drugs for Alzheimer’s disease and other dementia,” stated senior author Daniel Geschwind, professor of neurology and psychiatry at the David Geffen School of Medicine at UCLA.

Genes for Tissue and Organ Regeneration Identified

Working on the genes of the fruit fly, Drosophila melanogaster, researchers from the University of Barcelona, Spain, described the genes and regulatory elements of their expression needed for tissue and organ regeneration. The research was published in the journal Genome Research

The article notes: “The resetting of gene expression patterns during response to injury is governed by coordinated actions of genomic regions that control the activity of multiple sequence-specific DNA binding proteins.”

The scientists analyzed the transcriptome of imaginal disks in the fruit flies’ wing during different regeneration time periods. Then they used massive RNA sequencing to identify the genes that were expressed differentially during the process. More than a third of those genes were located in specific gene clusters. 

“This study shows the growing importance of omics and bioinformatics to understand basic biological processes,” stated Cecilia Klein, a post-doctoral researcher with the Centre for Genomic Regulation (CRG) at the University of Barcelona.

Universal Cancer Detection Test?

Researchers from the University of Queensland’s Australian Institute for Bioengineering and Nanotechnology (AIBN) have identified a nano-scaled DNA signature that seems to be common to all cancers. The researchers’ work was supported by a grant from the National Breast Cancer Foundation. The study was published in the journal Nature Communications.

The scientists looked at epigenetic patterns in cancer cell genomes and in healthy cells, looking specifically for methyl groups. Methyl groups are spread across the genome, but the AIBN team found that cancer cells’ genomes often lack methyl groups except for “intense clusters of methyl groups at very specific locations.” The researchers dubbed this the cancer “methylscape,” and they observed it in every type of breast cancer they studied, as well as in other cancer types, including prostate cancer, colorectal cancer and lymphoma.

“Virtually every piece of cancer DNA we examined had this highly predictable pattern,” stated Trau. “It seems to be a general feature for all cancer. It’s a startling discovery.”

As part of their work, they discovered that when these methylscapes, in a solution, make cancer DNA fragments fold into three-dimensional nanostructures—and these nanostructures like to attach to gold.

With that knowledge, they designed a lab test that uses gold nanoparticles that change color depending on if these 3D nanostructures of cancer DNA are present. It can be performed on a single drop of blood.

Gene Therapy Reverses Sickle Cell Anemia

Researchers with Cincinnati Children's Hospital Medical Center used a gene therapy on two adults and presented data at the American Society of Hematology (ASH)’s annual meeting this week.

“One year after treatment of our first patient, and six months after treatment of our second patient, both have seen a remarkable improvement in the quality of life due to remarkable reduction in disease symptoms,” stated Punam Malik, director of Cincinnati Children’s Comprehensive Sickle Cell Center. “This includes near elimination of chronic pain and sickling events and improved anemia. Although it’s still early post-treatment, these preliminary results are quite promising. If sustained, this therapy will provide a transportable, safe and feasible gene therapy for all SCA patients.”

The gene therapy utilizes a modified gamma globin lentivirus vector to transfer a healthy fetal hemoglobin gene. Cells are collected before the procedure from the patient, genetically reprogramed with the vector. The patient’s bone marrow is preconditioned with a low dose of chemotherapy, then the modified cells are infused into the patient. Within seven to 10 days, the patient’s blood counts recover, and from the chemotherapy they usually recover in about two weeks.

Cincinnati Children’s teamed with Roivant Sciences to create Aruvant Sciences, which is developing the gene therapy.

Eliminating a Single Gene in Mice Controls Obesity

Researchers at Flinders University in Australia, working with mice, removed a single gene known as RCAN1 and then fed them a variety of diets, including a high-fat diet. The mice did not gain weight, even after dramatically overeating high-fat foods over several weeks. The research was published in the journal EMBO Reports.

RCAN1 stands for Regulator of Calcineurin 1. This is a feedback inhibitor of the calcium-activated protein phosphatase calcineurin (CN) and suppresses two different mechanisms of what is called non-shivering thermogenesis (NST). An increase in NST burns calories as heat instead of storing them as fat. The first mechanism involves activating UCP1 expression in white fat. The second is mediated by sarcolipin (SLN) in skeletal muscle.

Basically, the mice whose RCAN1 gene was removed, were better at converting white fat into the healthy energy-burning brown fat. This even happened when the mice were at rest.

“We have already developed a series of drugs that target the protein that this gene makes,” stated Damien Keating, who led the international research group, “and we are now in the process of testing them to see if they inhibit RCAN1 and whether they might represent potential new anti-obesity drugs. In light of our results, the drugs we are developing to target RCAN1 would burn more calories while people are resting. It means the body would store less fat without the need for a person to reduce food consumption or exercise more.”

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