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

December 1, 2022

HIV vaccine succeeds in phase 1 clinical trial

If there was a spectrum of vaccine target success, COVID-19 would obviously sit on one far end of it. HIV/AIDS, on the other hand, sits at the opposite end of that spectrum—the desperate end. It’s been more than 50 years, and we’re still chasing the first vaccine. New hope this week comes from researchers at National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, Scripps Research Institute in La Jolla, California, and the Fred Hutchinson Cancer Center in Seattle, who report the first human success with a nanoparticle vaccine that uses a novel immunization strategy they call “germline targeting.” In a phase 1 clinical trial involving 48 people, the vaccine proved safe, and it induced broadly neutralizing antibodies—something considered absolutely necessary for any future HIV vaccine. Science

Editor’s note: proto.life editorial director Jason Socrates Bardi was formerly a writer at NIAID and Scripps Research and wrote press releases about HIV vaccine design efforts at both places.

Alzheimer’s drug shows promise, slows disease

The data look promising: In an 18-month, phase 3 trial of 1,795 people with early Alzheimer’s disease, a new monoclonal antibody drug called lecanemab successfully reduced amyloid levels in their brains and appeared to give them the benefit of moderately less cognitive decline—albeit with some concerning side effects. The researchers at Yale who conducted the trial are cautious. “Longer trials are warranted,” they write. That hasn’t stopped some in the media from swooning. And nothing could stop doctors, patients, caregivers, and everyone else who cares about this disease from having hope. Still, we are cautious. Lecanemab is being developed by Boston biotech behemoth Biogen and Tokyo pharma giant Eisai—the same two companies that gave us aducanumab (Aduhelm), winning FDA approval over the objections of its own advisory board in a storm of controversy. That may not happen again, Science magazine is reporting, since apparently the FDA has no plans to convene a panel this time around. NEJM

Senescent neurons in the brains of people with Alzheimer’s disease

Researchers at the Salk Institute for Biological Studies in La Jolla, California, have found evidence of increased senescent neurons in the brains of people with Alzheimer’s disease, possibly indicating these cells are involved in the disease’s pathology. Looking at post-mortem tissue samples of the prefrontal cortex taken from 30 people with Alzheimer’s compared to samples taken from 99 people without the disease, they found molecular signatures indicating people with Alzheimer’s may harbor more of these senescent neurons. They also demonstrated senescent neurons could be targeted and eliminated with drugs—something that “could be a strategy for preventing or treating Alzheimer’s disease,” the researchers write. Cell Stem Cell

Green neurons with blue nuclei from a person with Alzheimer’s disease. Salk Institute

Microbes in your gut control binge eating

Just in time for the holidays, a tantalizing picture of how the gut microbiome controls feeding emerged this week from a study in mice at Caltech. Researchers there showed that when the gut microbiomes of mice are depleted by antibiotics, they overconsume high-sucrose food pellets. But when their microbiotas are replenished with fecal transplants from healthy mice, their binge eating stops. The scientists traced the effect to activity in the “reward” areas of the rodents’ brains—the ventral tegmental area and the nucleus accumbens. They also narrowed the effect to two specific types of gut bacteria, from the family S24-7 and the bacterium Lactobacillus johnsonii, showing their levels alone were sufficient to induce or reduce the antibiotic-induced binge eating. Humans are likely to have similar mechanisms at play in our gut-brain behavioral axis, and some studies have already identified altered gut microbiomes in people with anorexia nervosa and other eating disorders. Current Biology

Poverty, brain structure, and psychological symptoms

A study of 7,569 adolescents aged 9–10 found that poverty is associated with an increase in “externalizing” psychological symptoms, such as aggression and hyperactivity. The association of lower socioeconomic status with those symptoms has been seen before, but the new work maps it to the brain. In part of the Adolescent Brain Cognitive Development Study, researchers at Harvard University have shown the association is partially explained by lower cortical surface areas and volumes among poor children compared with wealthier peers across widespread brain regions—areas of executive function as well as visual, auditory, emotional, and language processing. But the crucial question remains: Why? If such structural differences are associated with poverty, what causes them in the first place? The researchers name the usual suspects: exposure to environmental toxins, neighborhood violence, domestic stress, and/or lack of access to enriching cognitive experiences at home and school. JAMA Network Open

Do Buddhist precepts lower depression?

A study of 644 people surveyed online from late 2019 to September 2022 in Thailand shows that people who adhere more closely to the so-called five precepts in Buddhism (to refrain from killing, stealing, sexual misconduct, malicious lies, and taking alcohol or drugs) were less likely to develop depressive symptoms. Though the study was small in size, relied only on self-reported outcomes, and limited to a single country with a widely dominant Buddhist culture, its authors suggest the work could be broadly applicable. Conducted by researchers at Chiang Mai University in Thailand and Károli Gáspár University of the Reformed Church in Budapest, they suggest it could inform behavioral interventions for mental health wellness in general. Even when stripped of their cultural or religious significance, mindfulness and meditation are increasingly recognized as meaningful tools for psychological resilience outside of their cultural origins. PLOS ONE

The five fingers of the Buddha’s hand representing the five precepts. Shutterstock

The gravity hypothesis of irritable bowel syndrome

A stunning new hypothesis about the origins of the chronic and often debilitating disorder irritable bowel syndrome, which affects as much as 10 percent of the population, suggests that its root cause is… gravity?! A doctor at Cedars-Sinai Medical Center in Los Angeles is proposing in a perspective this week that irritable bowel syndrome results from “ineffective anatomical, physiological, and neuropsychological gravity management systems.” Our intestinal tracts are evolved for form, function, and integrity tradeoffs that help us to survive in a cruel, chaotic world and yet sometimes leave us ill-equipped to deal with that most fundamental physical force in our gravity-bound world. “It is hoped that the ideas in this thought experiment may also help encourage new or different ways of thinking about this common disorder,” he writes. The American Journal of Gastroenterology