The most common genetic risk factor for Alzheimer’s disease disrupts brain function in healthy, older women but has little impact on brain function in healthy, older men. The findings, revealed in a study published June 13 in the Journal of Neuroscience, may help explain why more women than men develop this disease, says the study’s senior author, Michael Greicius, MD.
For every three women with Alzheimer’s, only about two men have the neurodegenerative disorder, says Greicius, an assistant professor of neurology and neurological sciences and medical director of the Stanford Center for Memory Disorders.
Women with the gene variant, known to be a potent Alzheimer’s risk factor, show brain changes characteristic of the neurodegenerative disorder that can be observed before any outward symptoms manifest.
Both men and women who inherit two copies (one from each parent) of this gene variant, known as ApoE4, are at extremely high risk for Alzheimer’s, a syndrome afflicting about 5 million people in the United States and nearly 30 million worldwide. But the double-barreled ApoE4 combination is uncommon, whereas about 15 percent of people carry a single copy of this version of the gene.
Greicius’ team demonstrated for the first time the existence of a gender distinction among outwardly healthy, older people who carry at least one copy of the ApoE4 variant. In this group, women but not men exhibit two telltale characteristics that have been linked to Alzheimer’s disease: a signature change in their brain activity, and elevated levels of a protein called tau in their cerebrospinal fluid.
Identifying the prominent interaction bet-ween ApoE4 and gender opens a host of new experimental avenues that will allow Greicius’ team and the field generally to better understand how ApoE4 increases risk for Alzheimer’s, he says. —Bruce Goldman
Life with a rare disease can be isolating, but a new film shows how patient-advocacy groups can provide a support network and spur researchers to look for cures.
Rare — directed by Maren Grainger-Monsen, MD, director of the Stanford Program in Bioethics, and Nicole Newnham, a filmmaker and writer in the program — focuses on Donna Appell and her daughter, Ashley, who has Hermansky-Pudlak Syndrome. HPS, a rare genetic disorder, often leads to albinism. Other symptoms can include blindness, bleeding problems, colitis and pulmonary fibrosis.
The film follows the Appells spreading the word about the Hermansky-Pudlak Syndrome Network and seeking enough patients for a drug trial. “It shows why the efforts of patient-advocacy groups really matter,” Grainger-Monsen says.
For information about ordering and viewing the film, Rare, visit http://www.rarefilm.org. — Susan Ipaktchian
Pediatricians at children’s hospitals increasingly treat the sickest of sick kids, with chronic illnesses, cancer, organ failure and congenital defects that would have been fatal just a few years back. To keep pace with the growing numbers and needs of these patients, and the needs of Northern California’s expectant mothers, Lucile Packard Children’s Hospital is growing, too.
On Sept. 6, Packard Children’s broke ground for an expansion to add 521,000 square feet and 104 beds to its 21-year-old pediatric and obstetric care hospital.
The $1.2 billion expansion, which opens in December 2016, is located at Quarry and Welch roads adjacent to Packard Children’s original 257-bed hospital. The construction site, now abuzz with jackhammers, bulldozers and cranes, will become a high-tech, environmentally friendly hospital surrounded by 3.5 acres of peaceful gardens and green space. — Erin Digitale
Opiates are the mainstay medication for easing pain, but because of side effects they don’t work well for everyone. Now a Stanford study shows that susceptibility to the worst of these side effects runs in families.
“One of the most hated side effects of these opiates, nausea, is strongly inherited,” says Martin Angst, MD, professor of anesthesia, who was a leader of the study published in the July issue of Anesthesiology. Slowed breathing, one of the most dangerous side effects, also was inherited, as was dislike for the drug, says Angst, director of the Stanford Human Pain Research Laboratory.
Researchers recruited 121 pairs of twins for the randomized, double-blinded and placebo-controlled study of opiates, a class of drugs that includes morphine, methadone and oxycodone. Heritability accounted for 30 percent of the variability for slowed breathing, 59 percent of the variability for nausea and 36 percent for drug disliking, which the researchers also tied to decreased likelihood for addiction.
“Our findings strongly encourage the use of downstream molecular genetics to identify patients who are more likely or less likely to benefit from these drugs — to help make decisions on how aggressive you want to be with treatment, how carefully you monitor patients and whether certain patients are suitable candidates for prolonged treatment.” — Tracie White
“It took us three years and 750 tries to make it work, but we finally did it,” says postdoctoral researcher Jerome Bonnet, PhD, who helped engineer a genetic equivalent of a binary digit — a “bit” in data parlance.
Bonnet and two co-authors published a paper June 5 in the Proceedings of the National Academy of Sciences describing how they used genetic engineering techniques to repeatedly encode, store and erase digital data within the DNA of Escherichia coli bacteria.
They’ve named their biotech data storage recombinase-mediated DNA inversion, or RAD, after the enzymatic processes used to cut, flip and recombine DNA within the cell.
They used RAD to modify a section of DNA that controls how E. coli fluoresce under ultraviolet light. The microbes glow red or green depending on the section’s orientation. Using RAD, the engineers can flip the section back and forth.
To create the system, the team had to balance the dynamics of two opposing proteins, integrase and excisionase, within the microbes. “Previous work had shown how to flip the genetic sequence irreversibly in one direction through the expression of a single enzyme,” Bonnet says, “but we needed to reliably flip the sequence back and forth.”
“The problem is that the proteins do their own thing. If both are active at the same time, or concentrated in the wrong amounts, you get a mess,” adds co-author Pakpoom Subsoontorn. After years of tinkering and testing, they got the balance right. The next goal is to go from the single bit to eight bits — or a “byte” — of programmable genetic data storage.
“I’m not even really concerned with the ways genetic data storage might be useful down the road, only in creating more scalable and reliable biological bits as soon as possible,” says assistant professor Drew Endy, PhD, the paper’s senior author. “Then we’ll put them in the hands of other scientists to show the world how they might be used.” — Andrew Myers
Government-funded community health centers, which serve low-income and uninsured patients, provide better care than do private practices. That’s the surprising conclusion of a study published in the August American Journal of Preventive Medicine by professor of medicine Randall Stafford, MD, PhD.
Stafford and researchers at UC-San Francisco examined records of 73,074 health-center visits to private practices and to Federally Qualified Health Centers and other government-supported centers where low-income and uninsured people get care. Community health center physicians performed as well as their private-practice colleagues in 13 of 18 measures of care and better in five of those measures.
That’s good news in light of the Affordable Care Act, which depends on community health centers to serve more patients. “If community health centers are going to be taking up some of the new demand, we can be confident that they’re giving relatively good care,” Stafford says. — Mandy Erickson
Doctors routinely give cochlear implants to deaf children as young as 1 year old. But what if children show signs of mental retardation and might never learn to talk? Does it make sense to implant “bionic ears” then?
Doctors usually don’t, but they should seriously consider it, says associate professor of otolaryngology John Oghalai, MD, who with colleagues studied the records of 60 developmentally delayed and 144 cognitively normal children who received cochlear implants.
The researchers found the implants could substantially benefit children’s intellectual development, even if they don’t learn to talk, he says.
The combination of deafness and developmental delay is increasingly common as more children survive extremely premature birth, which often results in both conditions, as well as many other impediments.
“If you can fix one of the sensory problems, it might help to mitigate the effects of the other disabilities,” they say. The research appeared in August in Otology & Neurotology. — Erin Digitale
Norbert von der Groeben
Stanford biochemist James Spudich, PhD, received the 2012 Albert Lasker Basic Medical Research Award for his investigations of the molecular motors that drive our skeletal muscle contractions and heartbeats, enable our cells to divide, and power patrolling immune cells through our tissues.
The prize, widely considered the American equivalent of the Nobel, carries an honorarium of $250,000, which Spudich, the Douglass M. and Nola Leishman Professor of Cardiovascular Disease, will share with two other researchers.
Molecular motors reside inside every cell in our bodies. These motors use the chemical energy of ATP — the small, ubiquitous molecule that serves as the body’s energy currency — to produce forward motion. Much as a car’s engine burns gasoline, these motors “burn” ATP by splitting it in two, liberating chemical energy that is then coupled to mechanical movement.
Clinical trials testing drugs based on Spudich’s understanding of how muscles contract offer hope for people prone to heart failure, amyotrophic lateral sclerosis and perhaps even the frailties of old age. “It would be great if a small-molecule drug that bound to skeletal-muscle myosin could strengthen muscles with minimal side effects and let you get out of a chair, or walk down the street,” he says. — Bruce Goldman