Week 34: Circadian rhythm and asthma, how IBM’s Watson is doing with helping treat cancer , and the latest happenings for the Animal Health industry.

Posted on August 31, 2018 in Uncategorized

Body clock breakthrough may result in new asthma drugs

The inflammatory response in asthma, arthritis, and cardiovascular disease is partly controlled by human circadian rhythms according to new research.

The authors say the findings – which were detailed in a study in PNAS last week – may allow developers to create therapies that target proteins involved in inflammation like NRF2, which is known to play a role in the excessive response seen in some diseases.

“Our findings uncover a clear role for the molecular clock in regulating NRF2 in innate immune cells to control the inflammatory response. These findings provide insights into the pathology of inflammatory conditions, in which the molecular clock, oxidative stress, and IL-1β are known to play a role.”

GEN welcomed the findings as important but stressed, after speaking with the researchers, that there is still much more work to be done to turn the data into drugs.

In its coverage NeuroScience News said the results suggest the efficacy of some disease treatments may differ depending on the time of day they are applied.

Likewise the Irish Times said the findings may explain why shift workers are more susceptible to inflammatory diseases than people who work 9 to 5 jobs.

Publication of the study comes days after other research suggested people whose circadian rhythms are disturbed are at greater risk of obesity and heart disease.

Elsewhere this week 

IBM Watson’s super computer has had multiple issues with recommended treatments for cancer patients according to the Wall Street Journal. In some cited cases, Watson was able to make recommendations, but patients had little to no response to the treatments it suggested. IBM is also broadening Watson’s scope to include Genomics and Clinical Trial Matching, stating that healthcare is the “most important target for AI.”

FiercePharma says Louisiana wants a ‘netflix’ model for hepatitis C medicines in which it would pay a fixed fee for unlimited access to drugs to treat Medicaid recipients and prisoners. The state submitted a request for comments on the matter earlier this month and is awaiting reply from drug makers. The hope is to control drug prices and increase access for underserved populations or for those who would otherwise not receive access to treatment.

Forbes reports from the KC Animal Health Corridor annual market insight seminar on the wave of mergers and acquisitions that are reshaping the industry. Other topics covered included the production livestock industry’s goal to listen to consumer demands and cut down or eliminate the use of antibiotics in their products.

Meanwhile, Animal Health industry experts are shifting their focus to creating life-enhancing and extending treatments for animals, echoing the increasing sentiment that pets are family too. Innovation in the industry has even included re-formulating successful human drugs for pet applications. In fact, Kindred Biosciences just released a new drug, Mirataz (mirtazapine transdermal ointment), which is used to manage weight loss in cats—not likely to have been a focus treatment for cats even as much as ten years ago. Kindred is also working on Zimeta, which is a pyrazolone anti-inflammatory drug to help control pyrexia is horses. It is currently submitted to the FDA for final approval, which is expected this year.  

There has been a drastic increase in pet expenditures in the US, with projections for the industry value to rise up to $72 billion this year.

Reuters looks at growing concerns about the regulation of small molecule active pharmaceutical ingredient (API) production in China in the wake of the valsartan crisis. Traces of NDMA, a known carcinogen, were found in the product during the “optimization and evaluation” phase of the manufacturing process back in June as a result of Zhejiang Huahai Pharmaceutical was looking to expand its production of valsartan. This discovery came after production standards were met by Chinese, European, and U.S. regulators.

Research news

According to Wikipedia, bacteria are a type of biological cell that constitute a large domain of prokaryotic microorganisms. Bacteria were among the first life forms to appear on Earth, and are present in most of its habitats.

It is not surprising that researchers remain intrigued by the powers of bacteria for good (and uncovering the mechanisms that lead to the bad) and how they may be applied to optimize human health and treat diseases. Lately we have seen a strong uptick in the interest in gut bacteria and what impact that has on multiple human factors, including overall health, weight, mental capacity, and even their influence on heavy-hitting diseases like cancer.

In a piece re-highlighted by Biotechniques newsletter last week, Scientists at the Center for Cancer Research at the National Cancer Institute (MD, USA) have revealed a connection between depleted levels of gut bacteria in mice and their Natural Killer T (NKT) cell antitumor response in the liver, which could help gain a better understanding of liver cancer and help to develop better therapies to treat it.

And on the viral front, the flu vaccine remains a hot topic as Pfizer announces a deal with BioNTech to develop an mRNA-based vaccine. As reported, this approach may prove easier to produce and more efficacious than existing vaccines but remains in early stages of discovery.

Meanwhile, GEN reported on a possible universal flu vaccine (also mRNA-based), which has long been an industry goal after yearly issues with flu vaccine strains or supply. In fact, University of Pennsylvania (UPenn) researchers hope to start clinical trials of a universal mRNA flu vaccine within the next two years, with the ultimate goal of eliminating the need for reformulation every year.

And finally, costimulatory domains key to CAR-T potency says study

The costimulatory domains in chimeric antigen receptors (CARs) have more of an influence on the efficacy of CAR-T therapies according to a study published in Science.

The study analyzed the differing domains in Kymriah and Yescarta – which are sequences derived from costimulatory proteins 4-1BB and CD28 respectively.

The results showed CAR-T cells engineered with CARs containing CD28 attack tumors more quickly and intensely. However, they also illustrated that – in animal studies – CAR-Ts made with 4-1BB bearing CARs cleared cancer cells more effectively.

The findings have implications for the production of future CAR-T therapies according to the authors who suggest the choice of costimulatory domain could influence characteristics such as side effect profile and duration of therapeutic action.

Phosphoproteomic analysis of chimeric antigen receptor signaling reveals kinetic and quantitative differences that affect cell function

DOI: 10.1126/scisignal.aat6753