Week 2: NSAIDs and C. diff, a new approach to pest control, and why certain dogs breeds can provide a biological model for human genetic diseases

Posted on January 15, 2019 in Drug Development

A New Link Between NSAID use and Clostridium difficile Discovered in Mice

Researchers at Vanderbilt University have uncovered new evidence suggesting the regular use of common NSAIDs may contribute to an increased severity of a Clostridium difficile (C. diff), a bacterium that causes gastrointestinal symptoms and is estimated to cause over 30,000 deaths per year. Commonly a hospital acquired infection, it usually occurs in patients who have been on antibiotics.

The use of antibiotics is said to negatively impact native microbiota populations in the intestines, which allows for the growth of C. diff. Now researchers are saying that NSAID use during an active infection may exacerbate symptoms and increase its severity.

The direct mechanism of action is not known between the two, but there has been evidence to show that NSAIDs cause a shift in the gut microbiota of both seemingly healthy humans and mice, as well as aggravate the gut of those suffering from inflammatory bowel disease. The thought is that NSAIDs block pathways to allow for normal expression of necessary hormones and signals that contribute to the health of intestinal epithelial cells. When these cells are not healthy, the tight junctions that block the transfer of pathogens become compromised and leaves the body vulnerable to infection.

Further studies are being called for to study any changes that can be made to drugs that can help combat this new discovery. Read more from GEN here.

FDA Approves First Inhaled Drug for Parkinson’s

Inbrija (levodopa) has been approved to treat OFF episodes in patients with Parkinson’s Disease (PD), as covered by In-Pharma Technologist. This breakthrough comes after “decades” of research by Acorda.

OFF episodes occur when dopamine levels are low in between doses of levodopa, causing hypomobility and impairing motor function. This inhaled version is said to help combat absorption issues or discrepancies that can occur with oral doses and is designed to be used as needed based off of the individual.

Inbrija is set to hit the US market in the first quarter of 2019.

Cabaletta Bio Closes $50M Series B Funding for CAAR-T Development

The funding will cover establishing translational research and the advancement of manufacturing capabilities, as covered by BioPharma-Reporter.

It will also go to cover funding for their clinical trial and IND submission for DSG3-CAAR-T, designed to help patients with mucosal pemphigus vulgaris, an autoimmune disease that causes painful blistering on the skin and mucous membranes. The trials are slated to start once approved by the FDA.

Working similarly to CAR-T, chimeric autoantibody receptor T-cells (CAAR-T) is designed to emit a chimeric autoantibody receptor on the surface of T-cells and display cytotoxicity to cells associated with antibody-mediated autoimmune diseases.

Cabaletta has raised $88M towards the CAAR-T product since May of 2018.

A New Solution to Controlling Pest Populations?

Scientists from UC Davis have developed a new method to control pest populations that carry disease or destroy crops, reported by GEN. This new method utilizes CRISPR-Cas9 methods of gene editing to produce progeny that are completely sterile.

Sterile insect techniques (SITs) have been used since the 1930s to mass produce sterile males by using DNA-damaging substances or other SIT technologies that can develop resistance through genetic manipulation. This new CRISPR-based method is considered precision-guided (pgSIT) and can deliver sterile male progeny who survive to adulthood, offering a cost-effective and seemingly safe way to control pest populations.

This new method will require less manual sorting of larvae and won’t require multiple production facilities, just that modified eggs are transferred to and hatched in the desired region, being released when ready.

Researchers hope to apply this technology to mosquito populations that transmit diseases like dengue fever, Zika, and yellow fever.

A Genetic Similarities Between Bulldog Breeds and Rare Human Disease Discovered

Researchers form UC Davis’ School of Veterinary Medicine have discovered a common gene in certain dog breeds and those people suffering from a rare genetic disease known as Robinow syndrome.

The gene in question, DISHEVELLED 2 or DVL2, is a variant found in 100% of bulldogs and French bulldogs studied, as well as some Boston terriers. The gene is responsible for giving these dogs their physical characteristics, such as small size, wide face, and their short, kinked tail due to a lack of vertebrae that make up a tail (commonly referred to as a “screwtail”).

These characteristics are similar with those suffering from Robinow syndrome, who typically have short limbs, wide faces, and spinal deformities. Interestingly enough, both species with DVL2 have the potential to suffer from cleft palate.

For dogs, their physical appearance is so tied to the breed that it would be hard to eliminate from future generations- most people love these breeds for their faces and lack of a tail. The wide face and shorter snout are referred to as brachycephalic and comes with other associated diseases such as cleft palate. Other genes have been known to contribute to these physical appearances and may also play a role in chronic diseases associated with bulldogs-like breeds.

The goal of this discovery is to provide a biological mode, and associated insight, to those suffering from Robinow syndrome. Since its discovery in 1969, only a few hundred cases have been reported.

Read more from American Veterinarian here.