The week’s most astounding developments from the neobiological frontier.

August 3, 2023

Your wearable could zap you to release insulin

A crucial step toward the development of wearable electronic devices that could modulate gene expression and ameliorate metabolic diseases such as type 2 diabetes was described this week by researchers at ETH Zurich in Basel, Switzerland. They implanted mice bred in the laboratory to mimic type 1 diabetes with insulin-producing human cells. Then using acupuncture needles energized for 10 seconds once a day with DC batteries that delivered about half the current you would get from a typical 9-volt, they showed they could induce insulin release in the mice and restore normal blood sugar levels. They call their invention direct current-actuated regulation technology (DART), and they write, “We believe [it] will enable wearable electronic devices to directly program metabolic interventions.” Nature Metabolism

Non-opioid pain drugs: Where do we go from here?

Let’s face it: One of the most compelling, defining, and unsolved medical problems of our day is acute human pain. It’s incredibly difficult to design a safe and non-toxic drug that blocks pain, and our inability to do so effectively threw open the doors to the opioid crisis and the massive, ongoing social and human health problems it created. And still so many millions of Americans suffer intractable pain. We have reported how several drug companies have abandoned efforts to develop a promising class of drugs, called Nav1.7 inhibitors, which block that sodium channel protein from transmitting pain signals to the brain. Now a new study from Boston-based Vertex Pharmaceuticals shows promising if mixed results for an experimental drug called VX-548, which blocks a similar receptor called Nav1.8. In two parallel phase 2 clinical trials, they showed the drug was effective for treating post-operative pain—but only at the highest doses tested and often at the cost of side effects like constipation and headaches. NEJM

International collaboration reveals genomics of HIV

One crucial variable influencing clinical outcomes for people with HIV/AIDS is something called “set point viral load.” It’s the amount of HIV in the bloodstream at the end of the initial phase of infection, and for decades we’ve known how profoundly it affects disease progression. People who have lower set points (and less virus) generally fare better later on and may be less likely to transmit the virus to others. Now an international team of scientists at the Public Health Agency of Canada in Winnipeg, Manitoba, Imperial College London, and EPFL in Lausanne, Switzerland, has uncovered how set point viral load is controlled genetically. Looking at the genomes of 3,879 people of African ancestry living with HIV, they identified certain genetic variations in the DNA near a gene called CHD1L in this population that appear to control HIV replication. This work may lead to better treatments, particularly in sub-Saharan Africa, where the majority of new infections occur every year. Nature

The drugs-for-bugs approach to diabetes

Researchers from China’s Peking University, Beijing Chao-Yang Hospital, and the National Cancer Institute in Bethesda, Maryland, have screened the intestinal microbiomes of mice with diabetes-like conditions and discovered the enzyme dipeptidyl peptidase 4 (DPP4) is expressed by specific bacteria in their gut microbiomes. This molecule’s activity appears to disrupt glucose metabolism in the mice, but existing drugs that target human DPP4 had little effect on the bacterial DPP4. So they used high-throughput screening to identify another compound, called daurisoline-d4 (Dau-d4), which they say is a selective inhibitor of microbial DPP4. Administering Dau-d4 improves glucose tolerance in diabetic mice, and they say it could be the basis for a targeted “drugs for bugs” approach to treating diabetes. Science

First clinical trial of kombucha for diabetes

The popularity of naturally fermented, helpful bacteria-rich kombucha has risen in part because of widespread beliefs in its health benefits. However, there is a dearth of actual clinical data showing such benefits—most data comes from animal or test tube studies. Now in a baby step toward better clinical data, a tiny pilot study involving 12 people at Georgetown University Medical Center in Washington, D.C., shows that drinking kombucha for several weeks could reduce blood glucose levels in people with type 2 diabetes. Despite those promising results, the pilot study was small, so it’s not possible to make definitive conclusions about the health effects of kombucha. “Larger follow-up studies are warranted,” the doctors write. Frontiers in Nutrition

Blood sugar levels for individual participants receiving kombucha or placebo. 7-day mean fasting blood sugar levels for subjects collected at baseline (B), week 1 (1), and week 4 (4) for each treatment. Results from each patient are color-coded across each study arm. Frontiers in Nutrition