Research Roundup: Huntington’s Mutation Linked to Frontotemporal Dementia and ALS and More
Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.
Mutation for Huntington’s Disease Linked to Frontotemporal Dementia and ALS
Researchers with the National Institutes of Health/National Institute of Neurological Disorders And Stroke found that a mutation known to cause Huntington’s disease is linked to frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Huntington’s disease and several other neurological disorders are associated with repeat expansion, a type of mutation that is kind of a genetic stutter, where certain amino acids in the DNA repeat abnormally. Huntington’s disease is the result of a sequence of three amino acids in the huntingtin gene repeats over and over again. The more repeats, the earlier the disease onset.
In a large international project, researchers screened the complete genomes from large cohorts of FTD/ALS patients and compared them to age-matched healthy individuals. Several patients had a well-established genetic marker for FTD/ALS appeared, but what caught everyone off guard was a small subset that had the same huntingtin mutation. They did not demonstrate classical symptoms of Huntington’s, but did for ALS or FTD.
“None of these patients’ symptoms would have clued their physicians into thinking that the underlying genetic cause was related to the repeat expansion we see in Huntington’s disease,” said Sonja Scholz, investigator, NINDS Intramural Research Program. “Our patients simply don’t match a textbook definition of disease when it comes to which mutation produces which symptoms. Here we have patients carrying a pathogenic huntingtin mutation but who present with FTD or ALS symptoms.”
There is a theory that since a gene therapy for that mutation is currently in advanced clinical trials, it may have applications to FTD or ALS patients with this particular mutation. There are also possible applications for additional genetic screening for FTD and ALS. The research was published in the journal Neuron.
FDA Report Confirms Pfizer-BioNTech’s COVID-19 Vaccine Efficacy
Although not exactly new research, the U.S. Food and Drug Administration (FDA), as part of the first day of its vaccines advisory committee meeting regarding emergency use authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine, released a 53-page report on Tuesday, December 8, 2020, that summarized data from their candidate vaccine trial. The data supports early data indicating the vaccine is safe and has an efficacy of 95%. The data also outlined how various diversity groups, including people over 65, those with pre-existing medical conditions like diabetes, and Black and/or Hispanic populations, were affected. The results show all appeared to be well protected. Approximately a third of the participants met the definition of obesity, which is lower than the general population of the U.S. The average age of volunteers in the trials was 51.
Eye Drop Designed to Deliver Drugs to the Retina and Other Back-of-the-Eye Tissues
Investigators with the Mass Eye and Ear of the Schepens Eye Research Institute developed an eye drop that can effectively deliver drugs to the retina and other tissues at the back of the eye. The experimental treatment is made up of nanoparticles called eNano-Ro5, and in their preclinical studies delivered a small molecule inhibitor of the transcription factor RUNX1 to the back of the eye. The excessive function of RNX1 has been linked by this same team of scientists to abnormal growth of blood vessels in people with proliferative diabetic retinopathy. In preclinical models reported in 2017, injection of the molecule curbed the aberrant vessel growth. In the new study, they packaged the drug into the nanoparticles and tested them in preclinical models of recurrent retinal detachment and proliferative vitreoretinopathy (PVR). eNano-Ro5 was effective in delivering the drug to the back of the eye, which decreased the severity of PVR.
COVID-19 Virus Particularly Well-Suited to Jump from Animals to Humans
Researchers at Duke University Medical Center studying the origin of SARS-CoV-2, the virus that causes COVID-19, found that it was particularly well-suited to jump from animals to humans. Genetic analysis found that its closest relative was a coronavirus that infects bats, but the ability to jump to humans was tied to a gene fragment from a coronavirus that infects the pangolin, a scaly mammal in Asia. The species-to-species ability to jump is caused by the virus’s ability to bind to host cells via changes in its genetic code. However, they found that the typical coronaviruses that infect pangolins are too different from SARS-CoV-2 to have directly caused the pandemic. But they do contain a receptor-binding site that allows the viruses to attach to a cell surface protein common on human respiratory and intestinal epithelial cells, endothelial cell and kidney cells. Although the viral ancestor in the bat is closely related to SARS-CoV-2, its binding site is significantly different, meaning that on its own it can’t efficiently infect human cells. They suggest that SARS-CoV-2 is a hybrid virus between bat and pangolin viruses.
Learning More About Which Immune Cells Offer COVID-19 Protection
With the Pfizer-BioNTech, Moderna and AstraZeneca-University of Oxford COVID-19 vaccines either authorized for emergency use or about to in different countries, researchers are still grappling with the exact types of immune responses needed to protect against the disease. Investigators from Beth Israel Deaconess Medical Center, working with monkeys, found that relatively low levels of antibodies offered protection in monkeys against the SARS-CoV-2 virus that causes COVID-19. They also investigated the role of CD8+ T-cells. They found that while antibodies alone can offer protection, including at relatively low levels, T-cells are also helpful if antibody levels are insufficient.
New Insulin Molecule Better Regulates Blood Sugar in Diabetes
Researchers at the University of Copenhagen and biotech company Gubra developed a new insulin molecule that they believe will eventually be able to better control type 1 diabetes. Currently, insulin on the market cannot tell the difference in type 1 diabetic patients if they need a small or large effect from the insulin. The new insulin molecule has a built-in molecular-binding capability that can sense how much blood sugar is in the body. As blood sugar increases, the molecule becomes more active and releases more insulin. As blood sugar decreases, less insulin is released. To date, it has been tested and been proven effective in rats. They are working to engineer the molecule so that it works more quickly and accurately before they can test it in humans.
New Form of Alzheimer’s Protein in CSF Identified
Investigators with Washington University School of Medicine discovered a novel form of tau, one of two proteins associated with Alzheimer’s disease (the other is beta-amyloid). The new type is MTBR tau, and the researchers believe it can be used to identify what stage of Alzheimer’s the person is in and track the progression of the disease. MTBR stands for microtubule-binding region tau. The disease starts when beta-amyloid begins forming plaques in the brain. This stage can last two decades or more without signs of cognitive decline. But soon afterward, tau tangles start to spread in the neurons, and the cognitive issues begin to appear and progress. The tau tangles can be detected by PET brain scans, but they are time-consuming and expensive. The study was published in the journal Brain.
“The MTBR tau fluid biomarker measures tau that makes up tangles and can confirm the stage of Alzheimer’s disease by indicating how much tau pathology is in the brains of Alzheimer’s disease patients,” said Randall J. Bateman, the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington School of Medicine in St. Louis. “If we can translate this into the clinic, we’d have a way of knowing whether a person’s symptoms are due to tau pathology in Alzheimer’s disease and where they are in the disease course, without needing to do a brain scan.”