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New Alzheimer’s suspect

Dadu ShinTB hideout

The pharmaceutical industry has spent billions of dollars on futile clinical trials directed at treating Alzheimer’s disease by ridding brains of a substance called amyloid plaque. But new findings by School of Medicine researchers have identified another mechanism, involving an entirely different substance, that may lie at the root not only of Alzheimer’s but of many other neurodegenerative disorders — and, perhaps, even the more subtle decline that accompanies normal aging.

Ben Barres, MD, PhD, professor and chair of neurobiology, is the senior author of a study, published in the Journal of Neuroscience, revealing that a protein called C1q steadily accumulates in healthy brains of aging mice and people, possibly predisposing them to disorders including Alzheimer’s and Parkinson’s.

“No other protein has ever been shown to increase nearly so profoundly with normal brain aging,” says Barres. Examinations of mouse and human brain tissue showed as much as a 300-fold buildup of C1q with advancing age.

He found C1q deposits heavily concentrated at synapses, which are the contact points connecting nerve cells in the brain to one another. These deposits don’t necessarily cause much damage themselves, says Barres, but the y may render synapses more prone to destruction by immune cells triggered by a brain injury, infection or other shock.

“The first regions of the brain to show a dramatic increase in C1q are places like the hippocampus and substantia nigra, the precise brain regions most vulnerable to neurodegenerative diseases like Alzheimer’s and Parkinson’s disease, respectively,” says Barres. —Bruce Goldman

Report card

Most of the students who chose to have their genome tested as part of a groundbreaking Stanford course on personalized medicine reported being pleased with their decision, according to a study by researchers at the School of Medicine.

While the sample size was small — 23 students in the class sent their saliva to a commercial genetics testing company; eight did not — 83 percent of those who chose to undergo testing said they were glad they did. Seventy percent said they had a better understanding of genetics as a result of having their own genomes tested.

The course, created in 2010, was one of the first in the country to give students the choice of personal genotyping as part of the curriculum. The study was published in PLOS ONE. — Tracie White

Stemmed cells

Stanford researcher Irving Weissman, MD, and his lab recently went searching for a kind of stem cell touted as an alternative to those derived from human embryos. The tiny cells, called very small embryonic-like, or VSEL, cells, were reported in 2006 as the only naturally occurring pluripotent cells in adult animals and humans. Since that time, the cells amassed some significant proponents, including the Vatican, which believes VSELs could provide all the benefits of embryonic stem cell research with none of the ethical controversy. A U.S.-based company called NeoStem plans to start a clinical trial to examine the cells’ potential to treat periodontal disease.

But there’s a problem: The cells don’t seem to exist.

Weissman published a study in Stem Cell Reports detailing efforts to identify the VSELs through a variety of procedures, including those described by the original researchers. Try as they might, his team was forced to conclude that the tiny “cells” are in fact a mixture of debris, and that the findings of pluripotency are wrong. Although some researchers disagree, it appears that these “very small embryonic-like” cells are nothing more than a cellular Bigfoot. —Krista Conger

Ear whacks

Dadu ShinUpfront

Long-term hearing loss from loud explosions, such as blasts from roadside bombs, may not be as irreversible as previously thought, according to a new study by researchers at the School of Medicine.

Using a mouse model, the study found that loud blasts actually cause hair-cell and nerve-cell damage, rather than structural damage, to the cochlea, which is the auditory portion of the inner ear. This could be good news for the millions of soldiers and civilians who, after surviving these often devastating bombs, suffer long-term hearing damage.

“It means we could potentially try to reduce this damage,” says John Oghalai, associate professor of otolaryngology and senior author of the study, published in PLOS ONE.

If the cochlea, an extremely delicate structure, had been ripped apart by a large blast, as earlier studies have asserted, the damage would be irreversible. “The most common issue we see veterans for is hearing loss,” says Oghalai.

The increasingly common use of improvised explosive devices around the world provided the impetus for the new study. Among veterans with service-connected disabilities, tinnitus — a constant ringing in the ears — is the most prevalent condition. Hearing loss is the second-most-prevalent condition. But the results of the study would prove true for anyone who is exposed to loud blasts from other sources, such as jet engines, car air bags or gunfire. —Tracie White

Nobel week

Nobel lightning struck twice this year at the medical school. On Oct. 7, Thomas Südhof, MD, professor of molecular and cellular physiology, won the 2013 Nobel Prize in Physiology or Medicine. A scant 48 hours later, Michael Levitt, PhD, professor of structural biology, won the Nobel Prize in Chemistry.

Südhof shared the $1.2 million prize with James Rothman, PhD, a former Stanford professor of biochemistry, and Randy Schekman, PhD, who earned his doctorate at Stanford under the late Arthur Kornberg, MD, another laureate.

Südhof and the others were awarded the prize “for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells.”

Rothman is now a professor at Yale, and Schekman is a professor at UC-Berkeley.

Levitt, shared the chemistry prize with Martin Karplus, PhD, of Harvard and the University of Strasbourg in France, and Arieh Warshel, PhD, of USC, “for the development of multiscale models for complex chemical systems.”— Rosanne Spector

Killer robots

Norbert von der GroebenUpfront

Drug-resistant superbugs are a well-known enemy to good health, especially in hospitals, with an annual $30 billion price tag estimated by the Centers for Disease Control and Prevention. Much hand-washing and chemical disinfectant has been thrown at the problem without complete victory.

This spring, Stanford Hospital & Clinics added mechanized assistance: Frost and Dazzle, two waist-high robots that deploy waves of sterilizing radiation to reach where human hands cannot. And, propelled by the same technology that drives strobe lights and lasers, the robots’ disinfection attack takes just a few minutes. — Sara Wykes

Rebuffing rape

Dadu ShinUpfront

In the slums of Nairobi, Kenya, as many as one in four adolescent girls are raped each year. But a recent study shows that a short self-defense course can dramatically reduce the girls’ vulnerability to sexual assault.

“Self-defense training taught these young girls to say ‘no’ with confidence, and empowered them to escalate their own defense to a higher level, if necessary,” says senior author Neville Golden, MD, professor of pediatrics at Stanford and chief of adolescent medicine at Packard Children’s.

The study, published online in the Journal of Adolescent Health, looked at 402 girls who participated in a program developed by a Kenya-based nongovernmental organization that taught them verbal and physical self-defense techniques. The program was designed to combat a culture in which discussing sexual assault is taboo.

In the 10 months after receiving the training, more than half of these girls reported using what they had learned to fend off would-be attackers. The proportion who were raped fell from 24.6 percent in the year before training to 9.2 percent in the 10-month period after.

The self-defense classes were also cost-effective: Providing the training cost $1.75 per student, whereas immediate after-care for rape in Kenya costs $86, a figure that does not account for long-term costs such as new HIV infections or unwanted pregnancies. — Erin Digitale

All squeak, no scamper?

The vast majority of published animal studies that led to clinical trials of treatments for neurological disorders were either poorly designed or biased in their interpretation, say Stanford study-design expert John Ioannidis, MD, DSc, and an international team of researchers.

They assessed more than 4,000 animal studies in 160 meta-analyses of potential treatments for several neurological disorders including Alzheimer’s and Parkinson’s diseases. They found that only eight of the meta-analyses yielded the statistically significant, unbiased data needed to support advancing the treatment to clinical trials. In contrast, 108 of the treatments were deemed at least somewhat effective at the time they were published.

Don’t turn up your whiskers at animal studies, though, says Ioannidis. They can be improved by increasing sample size, being aware of statistical bias, publishing negative results and making all the results of all experiments on the effectiveness of any treatment freely accessible. The study was p ublished in PLOS Biology. — Krista Conger








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