Stanford News

Think of it as the “Rocky” RNA. Researchers here at the School of Medicine have found that a small piece of RNA, called a microRNA, plays a key role in determining when muscle stem cells in mice start to divide. It’s the first time a microRNA has been implicated in the maintenance of the adult stem cell resting state.

According to our news story:

“Although on the surface the quiescent state seems to be relatively static, it’s quite actively maintained,” said Thomas Rando, MD, PhD, professor of neurology and neurological sciences. “We’ve found that changing the levels of just one specific microRNA in resting muscle stem cells, however, causes them to spring into action.”

The findings are potentially important because:

Unlike stem cells in the blood or skin, muscle stem cells spend most of their lives nestled in the surrounding tissue. “They don’t do much most of the time,” said Rando. “They remain in a quiescent state for most of a person’s life. When you injure your muscle, however, they begin dividing to repair the damage.” Like all adult stem cells, each muscle stem cell becomes two daughter cells: one with stem cell properties, and the other that continues dividing to become mature muscle cells and fibers to replenish those that are damaged. Without such “asymmetric” division, the stem cells would quickly be depleted after injury.

Pinpointing exactly what calls the stem cells to begin dividing is an important first step to using them in human therapies. It’s also a key to understanding how muscles age and why they become less able over time to repair normal wear and tear.

Rando and his collaborators have published their findings in Nature.

Engineers at Stanford have developed a tiny wireless chip, driven by magnetic currents, that is small enough to travel inside the human body. In the above video, Ada Poon, PhD, an assistant professor of electrical engineering, and colleagues describe how the device can propel itself though the bloodstream. They also discuss its wide range of potential biomedical applications, including delivering drugs and cleaning arteries.

Via Stanford Report

When Stanford neurosurgeon Gary Steinberg, MD, PhD, injected human stem cells this fall into the damaged spinal cord tissue of specially-selected patients, it was considered a major step forward in moving research discoveries toward clinical application. In November, however, the Menlo Park-based Geron Corp. announced it was ending the trial and its research into stem cells to concentrate on cancer drugs. Steinberg was disappointed, as many were. But, as he explained in a new Q&A on the Stanford Hospital & Clinics website:

We should remember that five of the anticipated eight total patients were successfully transplanted with no adverse effects noted to date. Since this was designed as a safety study, the outcomes are very encouraging. These patients will be followed for 15 years to assess continued safety as well as any signs of neurologic improvement. I don’t believe the early termination of enrollment in this study will significantly set back the stem cell therapy field.

And when asked about his personal motivation to pursue and study embryonic stem cell treatment, he told me:

I was inspired by what I see every day: Patients devastated by neurological disorders and psychiatric disease with no hope or little hope for recovery of function. And it’s been like that for hundreds of years for many neurological diseases or injuries, including stroke, degenerative disorders like Parkinson’s, brain tumors, Alzheimer’s. These patients are disabled and we have no treatment once the injury has occurred to restore or regenerate function. Stem cell therapy offers great hope to change that status for a large number of patients.

Previously: First California patient treated in Geron’s human embryonic stem cell trial and Stanford joins first human embryonic stem cell trial

Gilbert Khalil’s exemplary fitness did not protect him against prostate cancer – after age 60, the risk rises for every man. Khalil, a project manager from Danville, took a very orderly approach to decide how to proceed after his diagnosis. He had watched his mother and brother endure the side effects of their cancer treatments, so he and his wife Stacee read everything they could. “They all had consequences,” he told me. “We decided we wanted to get a second or even a third opinion.” The couple ended up at Stanford, talking with Mark Gonzalgo, MD, PhD, director of robotic-assisted urologic cancer surgery. This video tells their story.

Using a computer model of hepatitis C, Stanford researchers have determined that two new virus-targeting drugs called protease inhibitors are a cost-effective way to treat patients with advanced disease. As my colleague explains in a press release:

The drugs, which came out in the summer of 2011, were designed to be taken in conjunction with the standard treatment, which itself is a combination of two drugs, an interferon and an antiviral called ribavirin. While the new triple therapies increase the chances of kicking the virus, they have more severe side effects — such as full body rash and rectal bleeding — and boost costs. Boceprevir adds $1,100 per week to the cost of treatment, and telaprevir adds $4,100 per week.

…

[The researchers] wanted to know when or if doctors should prescribe the new treatments. Should doctors prescribe them to all hepatitis C patients? Or, should only patients with advanced disease be treated with the new drugs? With such high costs, the answers could have sweeping impacts on health-care budgets, particularly for public health systems such as the Department of Veterans Affairs hospitals where many hepatitis C patients receive care.

As described further down the release, intense statistical and simulation analysis led to the researcher’s conclusion:

Despite the large price tag and side effects, the new treatments help [patients with advanced disease] avoid costly cancers and liver transplants — as well as allowing them to live longer, higher-quality lives.

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The closer the threat of severe disease, the more justified treatment costs and risks become, said [lead researcher Jeremy Goldhaber-Fiebert, PhD]. “That would be the bottom line.”

The study appears in the current issue of Annals of Internal Medicine, which also features research showing that more people in the U.S. die from hepatitis C than HIV.

Previously: Drugs offer new hope for hepatitis C, Program examines hepatitis C, the “silent epidemic” and Hepatitis C virus’s Achilles heel

Though it’s easy to focus on the challenges of an aging society, Stanford’s Laura Carstensen, PhD, believes the benefits shouldn’t be overlooked. In a talk today at the annual meeting of the American Association for the Advancement of Science, Carstensen, as outlined in a Stanford Report article, discussed how we might gain from the talents and experience of our elders:

“We have presumed, even in science, that age is associated with decline,” she said. “But it turns out that’s not true. The profile for aging is much more nuanced. There is decline, but there are also improvements – in emotional functioning, improvements in knowledge.

“If you have a large population of emotionally stable, knowledgeable and relatively healthy old people, that’s a good resource.”

Of course before we can tap into this resource, we need to apply science and technology to solve the problems of older people:

Sustaining the health of an aging population is an obvious issue. Carstensen identifies chronic, long-term diseases as a much bigger problem today than before. Most of the medical advances in the last century involved acute diseases that affected mainly young people, she said. There has been less progress on chronic diseases that inflict old people, like diabetes, arthritis and osteoporosis.

“Flash back 100 years, this wasn’t a big problem,” she said. “It wasn’t a big problem for society or most individuals, because you were dead before you would get those diseases. But today, they are problems.”

Carstensen is director of the Stanford Center on Longevity.

Previously: Video from Stanford’s longevity roundtable now available and The effects of an aging planet

Here’s some very exciting news from Larry Chu, MD, the executive director of the Stanford Medicine X conference:

I am so pleased to announce that the iconic American architect Michael Graves will give the opening keynote address at Stanford Medicine X on September 29, 2012. Paralyzed from the chest down due to a central nervous system infection in 2003, Graves has since used his design acumen to reshape the hospital experience by leading a functional and aesthetic transformation of hospital furnishings and equipment. I can’t think of a more fitting speaker to open a conference on patient-centered innovation of health care at the intersection of emerging technologies!

The Medicine X conference will take place on Sept. 29 and 30, with a special pre-conference workshops day scheduled for Sept. 28. A list of other confirmed speakers is available on the conference website.

Photo courtesy Michael Graves

More news about Stanford Medicine X is available in the Medicine X category.

Huntington’s disease is a progressive, fatal neurological disorder with no cure. But now researchers at the National Yang-Ming University in Taiwan and Stanford’s School of Medicine have discovered a protein that may one day be a viable therapeutic target for those afflicted with the condition. According to co-senior author Tzu-Hao Cheng, PhD, associate professor at National Yang-Ming University’s Institute of Biochemistry and Molecular Biology:

Huntington’s disease is a devastating disease with no cure available at this time. Targeting the transcription factor identified in our research may one day be able to prevent or delay the formation of the protein aggregates that are the hallmark of this and other neurodegenerative diseases. We are hopeful that our studies will be a major advance in the field.

The research will be published tomorrow in the journal Cell. It was a joint collaboration between Cheng’s laboratory and that of Stanley N. Cohen, MD, professor of genetics here at Stanford. The findings are exciting because they suggest there may be a way to prevent the tangled clumps of huntingtin protein that cause the disorder.

About one in 10,000 people of western European descent have Huntington’s disease, which is particularly heartbreaking because of the slow but inevitable decline in sufferers’ physical and mental capacity. The disorder is characterized by uncontrollable movements, mental deterioration and eventual dementia. It’s genetic, and a child of an affected parent has a 50 percent chance of also developing the condition.

The advent of genetic testing has allowed people to know whether they carry the gene years before symptoms begin (usually in mid-life), but the lack of a cure or any kind of treatment has sparked discussion as to the utility of early diagnosis.

People with the condition have long stretches of repeats of the same three nucleotides in their huntingtin gene. Unaffected people have between eight and twenty-five repeats of the nucleotides cytosine, adenine and guanine, or CAG; the genes of affected people have 36 or more of these genetic stutters. As a result, the mutant protein has an extended region of glutamine, which is sticky and binds to itself and to similar regions in other huntingtin protein molecules to create clumps of useless protein that can severely damage nerve cells and lead to the disease.

In the current study, the researchers identified a molecule in yeast called Spt4 (or Supt4h in mammals) necessary to transcribe the huntingtin gene into protein. Interfering with the function of Supt4h reduces the amount of huntingtin protein in mouse cells that mimic the disease, as well as the number of protein clumps. Although any human trials are far off, there are intriguing glimpses of a pathway to possible therapy. According to the study:

Together these observations argue that agents targeting Supt4h may reduce the transcription of genes containing lengthy trinucleotide repeats while having limited effects on normal mammalian cell function.

Previously: New insights into protein folding could aid in developing therapies for neurodegenerative diseases
Photo by MJ/TR

For treating prolonged seizures outside a hospital setting, a quick intramuscular shot of anti-convulsant medication with an auto-injector, a kind of spring-loaded syringe, is as effective — if not more effective — than starting an intravenous line to administer the medicine directly to the bloodstream.

That’s according to findings from a first-of-its-kind study by researchers at Stanford and 16 other universities and hospitals nationwide. Their work appears in the New England Journal of Medicine.

The finding is important because giving a shot into the muscle of someone who is convulsing is generally safer and less time-consuming than starting an IV, said James Quinn, MD, a professor of emergency medicine here and a study investigator.

The intravenous route has always been considered the gold standard for treating status epilepticus in the field. But, as Quinn pointed out, “If patients are having a grand mal seizure, it can be tough to find a vein and get the medicine started, and it may increase the chance of a needle-stick injury either to the patient or medic.”

The aim of this study was to gather and compare data on the safety and efficacy of the shot, which administers midazolam, a sedative, versus the IV drip, which administers lorazepam, a similar sedative. As described in a National Institutes of Health release:

The study found that 73 percent of patients in the group receiving midazolam were seizure-free upon arrival at the hospital, compared to 63 percent of patients who received IV treatment with lorazepam.  Patients treated with midazolam were also less likely to require hospitalization than those receiving IV lorazepam.

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[The study] involved more than 79 hospitals, 33 emergency medical services agencies, more than 4,000 paramedics and 893 patients ranging in age from several months old to 103.

An interesting, behind-the-scenes aspect aspect of the research: Because they were the first responders, roughly 250 firefighter-paramedics in Santa Clara and San Mateo Counties had to be trained on how to conduct the clinical trial. “It required tremendous coordination,” Quinn told me. “For most of the firefighters, it was the first time they had done research. They did a great job, and I am proud of the job they and our research team did in this unique endeavor.”

Photo by gregfriese

Updated 4:15 pm: In his ongoing effort to push for a public health campaign to battle our country’s pain epidemic, Philip Pizzo, MD, dean of the School of Medicine, traveled to Washington D.C. to speak before the U.S. Senate Committee on Health, Education, Labor & Pensions today.

During the hearing, Pizzo highlighted the results of last June’s Institute of Medicine Committee report on pain, which concluded that the effective treatment of pain demands a “cultural transformation” on the part of patients, physicians and researchers. Pizzo chaired the committee that issued the report.

The total costs of treating pain are higher than the costs of cancer, cardiovascular diseases and diabetes put together, while the treatments still leave many patients suffering needlessly. In order to battle this epidemic, the government needs to support a public health campaign that includes improving education of providers, patients and communities, Pizzo and his co-authors concluded.

“The magnitude is simply astounding,” Pizzo told the committee. While the report focused on the public health implications of this epidemic and recommendations for change, the authors also understood that “it’s the individual human impact of pain that underscores why this is such an important issue…”

The effect on the individual was brought into stark focus by speaker Christen Veasley, an advocate for pain research who had a near-fatal accident 15 years ago and has suffered from residual back and neck pain ever since.

“For many of us, we wake up and the first thing we feel is pain,” she said. “It feels like you live with a veil over your face. As patients, we’ve been left completely disillusioned… This report has brought us renewed hope.”

Also testifying were John Sarno, MD, professor at New York University School of Medicine and William Maixner, PhD, director of the Center for Neurosensory Disorders at the University of North Carolina at Chapel Hill.

Previously: A call to fight chronic-pain epidemic and Relieving Pain in America: A new report from the Institute of Medicine

To celebrate Valentine’s Day, quarterly DVD magazine Wholphin has released a short film documenting an experiment by Stanford neuroscientists to determine if it’s possible for one person to love more than another person can.

In the film, titled The Love Competition, researchers at the Stanford Center for Cognitive and Neurobiological Imaging use functional magnetic resonance imaging (fMRI) to measure the brain activity of seven people as they ponder love. Bob Dougherty, PhD, research director at the center, helped develop the love test and Stanford psychology postdoctoral fellow Melina Uncapher, PhD, served as scientific director for the film.
Wired reports:

It turns out — based on the levels of activity in the dopamine, serotonin and ocytocin/vasopressin pathways — it is possible for one person to exhibit that they can love someone more deeply than another person can. But what’s amazing about The Love Competition is seeing the participants talk about their loves and the effects the fMRI tests had on them. Many come out almost giddy when the test is complete, and one woman tearily explains that she just feels lucky for the love she’s had in her life.

The film is definitely worth watching. Personally, my favorite contestant is 10-year-old Milo.

Previously: Ask Stanford Med: Neuroscientist taking questions on pain and love’s analgesic effects, Long-term love may dull pain, study shows and Love blocks pain, Stanford study shows

Some exciting news from Medicine X: The six core themes for the 2012 conference have been announced. They are:

• Design Thinking: Patient-Centered Design
• The Networked Patient: Communities of Practice and Participatory Medicine
• The Curators: Telling Stories and Making Sense of Health Information on the Internet
• The New Scientist: New Models of Scientific Discovery and Publishing
• mHealth and Gamification: How Mobile is Changing Everything
• The Interconnected Life: Emerging Technologies and the Future

The conference is also in the process of accepting papers for presentation. The submission period ends Apr. 15.

More news about Stanford Medicine X is available in the Medicine X category.

My colleague Erin Digitale tells the remarkable story today of a tiny Lucile Packard Children’s Hospital heart patient named Jaya Maharaj. Weighing just 3.5 pounds, with a heart slightly bigger than a walnut, the baby received a pacemaker shortly after birth and was “smaller than any pacemaker recipient ever reported in the medical literature.”

Digitale writes in Inside Stanford Medicine:

Jaya’s surgery is remarkable not just because of her small size but because many fetuses with her condition, congenital heart block, do not survive pregnancy. Research has shown that 20 to 50 percent of patients diagnosed prenatally die in utero or in the first weeks after birth. Yet premature delivery to implant a pacemaker carries its own hazards. When Leanne Maharaj, Jaya’s mom, was first referred to Packard Children’s Hospital from her hometown of Hayward, Calif., at 28 weeks pregnant, her doctors weighed the conflicting risks.

“We knew that at any time the baby’s heart could give out,” said neonatologist Valerie Chock, MD, a member of the large, multidisciplinary team that planned Jaya’s birth and surgery. “We had to decide: At what point do we deliver to balance that risk against the risk of premature delivery?”

The baby was ultimately delivered nine weeks early and went into surgery just 15 minutes after being born. And then:

After surgery, Jaya spent six weeks in the Neonatal Intensive Care Unit. With her heart pumping properly, she grew rapidly and was able to go home on Jan. 12. Her prognosis is excellent: Her pacemaker leads must be repositioned occasionally as she grows, and she will need new pacemaker batteries every five to seven years, but otherwise she will be able to lead a normal life.

Photo by Norbert von der Groeben

As much as I would love to lose 20 pounds in six weeks, you won’t find me signing up for of one of the latest weight-loss fads called the “HCG diet.” The Human Chorionic Gonadotropin diet is one that requires that you inject yourself daily with a hormone produced by pregnant women (a product that is only licensed for fertility treatment, not weight loss) and that you restrict yourself to eating only 500 calories a day. Neither thing is appealing to me.

Experts have concerns about – and are skeptical of – the potentially dangerous diet, as well. As John Morton, MD, director of bariatric surgery and surgical quality at Stanford Hospital & Clinics, told viewers in a recent KTUV-TV report:

“I would say the mind is a very powerful thing. And I would say there’s a big placebo effect occurring here.”

For more on HCG, FDA has information on its website.

Stanford psychology researchers are using imaging techniques to learn more about what happens in the brains of young girls at risk of depression and, as recently described here, they’re exploring a novel way to train brains away from negative situations. Ian Gotlib, PhD, discusses the work, which represents a “critical step in learning how to prevent the onset of a depressive episode,” in a Stanford Report article and the video above.

And for more on the topic, my colleague recently reported on adolescent depression and efforts to prevent it in Stanford Medicine.

Previously: Using brain-training games to stave off depression in adolescents