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Bioengineering, Cancer, Infectious Disease, Precision health, Research, Stanford News

Stanford scientists co-opt viral machinery to create medical delivery system

Stanford scientists co-opt viral machinery to create medical delivery system

James Swartz

Stanford engineering researcher James Swartz, PhD, and his colleagues have remodeled a hepatitis B virus to turn it into a microscopic taxi for medical therapies. The team stripped the virus of its pathogenic DNA and modified an outer shell so that they could “hang” molecular tags on the outside to help deliver vaccines or other therapies to specific cells. The researchers reported their findings in a paper in the scientific journal Proceedings of the National Academy this week.

They call the engineered product a virus-like particle (as opposed to a real virus with infectious material) or a smart particle. “We make it smart by adding molecular tags that act like addresses to send the therapeutic payload where we want it to go,” Swartz said in a Stanford News story.

The smart particle is a novel way to deliver vaccines or cancer therapies by teaching the body’s immune cells to recognize pathogens or cancer cells. Alternatively, the smart particle can deliver medicine specifically to the cells that need it.

Swartz and his colleagues’ effort is part of a larger field of targeted therapies that aims to precisely deliver therapies to the cells that need them and avoid damaging nearby healthy cells. Current cancer therapies, for example, are effective at fighting malignant cells, but also kill off healthy cells. That’s why cancer therapies often have such devastating side effects. But previous attempts to create virus-sized delivery systems have not been successful. In fact, Swartz’s team had a hard time getting funding for the early stages of this project because of previous failed efforts by other scientists.

So far, Swartz and colleagues have created the self-assembling shell that is invisible to the body’s natural immune defenses and strong enough to weather conditions in the blood stream and get its packaged contents to its destination inside the body. Next, they’ll work on putting specific cancer-fighting tags on the shell.

The most challenging task will be to pack the shell with a tiny dose of medicine. But Swartz sounded optimistic about his team’s goals. “I believe we can use this smart particle to deliver cancer-fighting immunotherapies that will have minimal side effects,” he said.

Previously: A less toxic, targeted therapy for childhood brain cancerIs cancer too complex for targeted therapies? and Working to create a universal flu vaccine
Photo, of Swartz holding an enlarged replica of a virus-like particle, by Linda Rice

Genetics, In the News, Mental Health, Neuroscience, Research, Stanford News

Bright Young Mind: Stanford postdoc featured as a top young scientist

Bright Young Mind: Stanford postdoc featured as a top young scientist
100315_nobels_rajasethupathy_resizedYoung researchers don’t always get the accolades they deserve, so I was delighted to see a recent story that’s bucking this trend. This week Science News released its list of “10 scientists who are making their mark,” and Stanford neuroscientist Priya Rajasethupathy, MD, PhD, a postdoctoral research fellow in the lab of Karl Deisseroth, MD, PhD, was featured among them.

Rajasethupathy was nominated for this honor by another group of outstanding scientists: Science News polled 30 Nobel Prize winners to learn which young researchers are doing work that’s worth watching.

Rajasethupathy’s research on how memories are made and stored caught their eye because she’s found that long-term memories may leave lasting marks on DNA. (Her work “has been called groundbreaking, compelling and beautifully executed,” according to the piece.) By studying sea slugs, she and her colleagues have also identified a tiny molecule that may be involved in memory.

Now Rajasethypathy is expanding on this early work and investigating the neural circuits involved in memory recall. To do this, she’s exploring specific genetic mutations to see if they result in abnormal memory behavior. This work may offer insights into neurological disorders, she explains.

Previously: Exploring the role of prion-like proteins in memory disordersNo long-term cognitive effects seen in younger post-menopausal women on hormone therapy and Individuals’ extraordinary talent to never forget could offer insights into memory
Photo by Connie Lee; courtesy of Pryia Rajasethupathy

FDA, Health Policy, Nutrition, Pediatrics, Public Health, Research, Stanford News

How much Bisphenol A is okay?

How much Bisphenol A is okay?


A new study came out this week that happened to remind me of one of my pet peeves about certain biomedical studies — choosing an “outcome” measure that doesn’t tell you what you really want to know. The study, which was led by Stanford postdoctoral fellow Jennifer Hartle, DrPH, and estimated the amount of BPA a child is exposed to in the course of a normal school day, was great. But her description of EPA safety tests on the plastics component Bisphenol A, or BPA — done back in the 1980s — made me think back to earlier work by University of California, Berkeley biologist Tyrone Hayes, PhD.

In the 1990s, the agricultural herbicide atrazine was safety tested by exposing frogs to low doses of atrazine as they developed from eggs to tadpoles to frogs. The adult frogs didn’t die or show obvious deformities such as extra legs, so the pesticide was deemed safe. But Hayes took a closer look and, in 2002, found that even at very low levels of atrazine exposure, male frogs were producing eggs instead of sperm.

So no gross deformities if you just looked at the frogs for 30 seconds. But in fact the animals had experienced a dramatic change in their health and biology. The lesson is that, in biology, sometimes the right outcome measure is something you have to really look for. There is a lot more to the Hayes-atrazine story.

But back to the current study: Hartle and her colleagues turned their attention to national school breakfast and lunch programs, which provide nutritious meals to 30 million kids every year but also deliver small amounts of BPA, an estrogen mimic that messes with hormones. Children’s meals are disproportionately packaged in tiny one-meal containers. Those tiny packages of apple sauce and juice have a greater BPA-emitting surface area than a big carton or can for the amount of food. And school kids often eat meals off plastic trays with plastic forks and spoons. For children who eat a lot of meals at school, it can add up.

According to Hartle’s paper, appearing today in the Journal of Exposure Science and Environmental Epidemiology, the question isn’t whether the kids are getting BPA in their meals — they are — but whether any of them are getting doses of BPA that could affect their long-term health. Based on those 1980s studies, the EPA estimates that BPA is safe at chronic exposure levels below 50 μg per kilogram of body weight per day. Happily, Hartle and her colleagues found that children are getting far less than that — as little as 0.0021 μg for a low-BPA breakfast to 0.17 μg for a high-BPA lunch. Everything should be hunky-dory, right?

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Events, Medical Education, Medicine X, Research, Stanford News, Technology

Medicine X 2015 kicks off this week with a focus on the theme “Great eXpectations”

Medicine X 2015 kicks off this week with a focus on the theme “Great eXpectations”

15146055376_5600a69df1_zThought-leaders and innovative thinkers will gather on campus this week for Medicine X. Stanford’s premier conference on emerging health-care technology and patient-centered medicine, the three-day event will be held at the Li Ka Shing Center for Learning and Knowledge and focus on the theme “Great eXpectations.”

Eric Topol, MD, chief academic officer at Scripps Research Institute, will kick off the conference on Friday with a keynote on democratizing medicine. Additional keynote speakers include Robert Pearl, MD, executive director and CEO of The Permanente Medical Group; and Peter Bach, MD, director of Memorial Sloan Kettering’s Center for Health Policy and Outcome. The program will also feature panels and presentations exploring the topics of precision medicine, aging, health and community and misconceptions and misperceptions in health care.

This year, Medicine X will be preceded by the first-ever Medicine X|ED conference. The two-day event, which begins on Wednesday, will examine the role of technology and networked intelligence in shaping the future of medical education. Digital media pioneer Howard Rheingold; Abraham Verghese, MD, vice chair for the theory and practice of medicine for Stanford’s Department of Medicine; and Sarah Stein Greenberg, executive director of the Stanford, will deliver keynote speeches at the conference. Medicine X|ED will focus on five core themes: Engaging millennial learners, opportunities and challenges for innovation in medical education, interdisciplinary learning, and how digital media and massive open online courses are redefining the educational landscape. Participants will also have the option to participate in a range of interactive and educational opportunities.

Those unable to attend the conferences in person can participate in the plenary sessions virtually through a high-quality streaming webcast; registration for the Global Access Program webcast is free. We’ll also be live tweeting the keynotes and other proceedings from the conference. You can follow our tweets on the @StanfordMed feed or follow the hashtag #MedX.

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

Previously: Medicine X conference to focus on the theme of “Great eXpectations”, Registration now open for the inaugural Stanford Medicine X|ED conference and Stanford Medicine X: From an “annual meeting to a global movement”
Photo by Medicine X

Clinical Trials, Mental Health, Parenting, Pediatrics, Research, Stanford News

Parents can help their teens recover from bulimia, say Stanford researchers

Parents can help their teens recover from bulimia, say Stanford researchers

Mom&teenTeenagers with bulimia nervosa benefit from their parents’ help in stopping their eating disorder. In fact, a therapy that involves parents works better for teens than one that does not, according to the first large head-to-head comparison in adolescents of two well-known bulimia treatments.

The findings are described in a study of 130 young people with bulimia that was published last week in the Journal of the American Academy of Child and Adolescent Psychiatry.

The research, which was jointly led by Stanford’s James Lock, MD, PhD, and a longtime collaborator, Daniel Le Grange, PhD, compared an approach tailored to teens with one commonly used in adults. In family-based therapy, the bulimia patient and a parent work together to stop the disordered eating behavior. In contrast, in cognitive behavioral therapy, which is widely recognized as the best approach for bulimic adults, there is more focus on changing abnormal thoughts about food and less emphasis on behavior change.

At the end of six months of treatment, 39 percent of patients in family-based therapy had abstained from the binge-and-purge cycle of bulimia for at least four weeks. Only 20 percent of those in the cognitive behavioral therapy group had done the same. The gap persisted six months after treatment ended, though it seemed to have closed by a year after the end of treatment.

Lock, who directs the Comprehensive Eating Disorders Program at Lucile Packard Children’s Hospital Stanford, said the findings are not surprising, given that teens are at a different stage of the illness and have different cognitive capabilities than adults with bulimia. But they are very important, since they suggest that the family-based approach is a faster way for young patients to recover from bulimia. From our press release about the study:

“The strategy for cognitive behavioral therapy requires a fair amount of abstract reasoning, motivation and persistence that often has not reached full capacity in teens,” [Lock] said, adding that doctors may need to decide on a case-by-case basis whether a teen would benefit from one treatment versus the other. “The cognitive and developmental context is very different for teens than for adult patients,” he said.

And it’s normal for teenagers to need their parents’ assistance in navigating difficult situations, he added. “The big take-home message is that families can really help their kids with bulimia nervosa.”

Previously: Family therapy an effective way to treat anorexic teens, Incorporating the family to help teens overcome eating disorders and Families can help their teens recover from anorexia, new study shows
Photo by J.K. Califf

Cancer, Genetics, Research, Science, Stanford News

Combination therapy could fight pancreatic cancer, say Stanford researchers

Combination therapy could fight pancreatic cancer, say Stanford researchers

I’ve mentioned here before my personal connection to pancreatic cancer, which claimed the life of my grandmother. So I was excited to hear from Stanford cancer researcher Julien Sage, PhD, about some developments on the research front. Sage and postdoctoral scholar Pawal Mazur, PhD, collaborated with Alexander Herner, MD and Jens Svieke, MD, at the Technical University Munich to conduct the work, which was published today in Nature Medicine.

In our release on the study, which was done in animal models, Sage explained:

Pancreatic cancer is one of the most deadly of all human cancers, and its incidence is increasing. Nearly always the cause of the disease seems to be a mutation in a gene called KRAS, which makes a protein that is essential for many cellular functions. Although this protein, and others that work with it in the Ras pathway, would appear to be a perfect target for therapy, drugs that block their effect often have severe side effects that limit their effectiveness. So we decided to investigate drugs that affect the DNA rather than the proteins.

Mazur and Herner worked together to test whether drugs that affect the epigenetic status of a cancer cell (that is, the dynamic arrangement of chemical tags on the DNA and its associated proteins that control how and when genes are expressed) could rein in its growth without serious side effects. Many of these tags are what’s called acetyl groups, and they are added to protein complexes called histones that keep the DNA tightly wound in the cell’s nucleus. As I explained in our release:

They started by investigating the effect of a small molecule they called JQ1 on the growth of human pancreatic tumor cells in a laboratory dish. JQ1 inhibits a family of proteins responsible for sensing acetyl groups on histones. The researchers found that the cells treated with JQ1 grew more slowly and displayed fewer cancerous traits. The molecule was also able to significantly shrink established pancreatic tumors in mice with the disease. However, it did not significantly affect the animals’ overall likelihood of survival.

Mazur, who began the work in Siveke’s lab and continued it when he moved to Sage’s lab, next tested whether using JQ1 in combination with any other medications could be more effective:

“It happened that the drug that worked best was another epigenetic drug called vorinostat,” said Sage. “On its own, vorinostat didn’t work very well, but when combined with JQ1 it showed a very strong synergistic effect in both the laboratory mice with pancreatic cancer and in pancreatic cancer cells from people with the disease.”

Vorinostat works by inhibiting a family of proteins that remove the acetyl groups from histones. It has been approved by the FDA for use in people with recurrent or difficult-to-treat cutaneous T cell lymphoma. When human pancreatic cancer cells were treated simultaneously with JQ1 and vorinostat, the cells grew more slowly and were more likely to die.

Mice with established pancreatic cancers treated with both of the drugs showed a marked reduction in tumor size and a significant increase in overall survival time. Their tumors showed no signs of developing a resistance to the treatment, and the mice did not develop any noticeable side effects.

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Fertility, Pediatrics, Public Health, Research, Sexual Health, Stanford News, Women's Health

IUD is overlooked as excellent birth control for teens, Stanford expert says

IUD is overlooked as excellent birth control for teens, Stanford expert says


When teenagers think of birth control, the pill and condoms are likely the first to come to mind – and indeed the pill is the number one choice of contraceptive among adolescents. But according to Stanford ob/gyn expert Paula Hillard, MD, the IUD is a long-acting reversible contraception (LARC) excellently suited for adolescents. In an editorial published in the October issue of Journal of Adolescent Health, Hillard urges doctors to consider the benefits of LARCs for young women.

The IUD and other LARCs don’t require consistent, correct daily use, so they’re easier to use and less likely to fail. In addition to being extremely effective, IUDs have a high rate of satisfaction among adolescents. Some types of IUDs can also be used therapeutically for problems like heavy bleeding or cramping. LARCs are also cost-effective over time, and the initial investment is no longer a barrier in California due to the Family PACT program, which allows teens to confidentially access birth control at no cost. In addition, the Affordable Care Act mandates that contraceptive methods must be covered in most cases without a co-pay.

So what are the barriers to use? They include misconceptions and lack of information on the part of both teens and providers, as well as provider concerns about the insertion procedure in young women who haven’t given birth.

In an email, Hillard told me:

Many physicians and most adolescents are unaware that modern IUDs provide contraception that is 20 times more effective than birth control pills, the patch or the ring. IUDs are a method of birth control that is very safe, very effective, and “forgettable”.  IUDs are considered to be “top tier” contraceptive methods (along with subdermal implants and sterilization, which is not appropriate for typical adolescents) by the American Congress of Obstetricians and Gynecologists and the American Academy of Pediatrics.

IUD use has increased from 0.5 percent to 2.5 percent among teens 15-19 years old over the past decade. Still, around 50 percent of obstetrician-gynecologists don’t consider an IUD as a first-line contraceptive for adolescents.

Hillard closes her piece with a discussion of the challenges and importance of counseling for adolescents. Proper counseling includes giving the most effective options priority, and discussing side-effects up front (which improves adherence to contraceptive regimens, including in adults). She writes:

It remains important for us as clinicians to fight for reproductive justice and contraceptive access for all women, with the elimination of barriers including costs. In our counseling, we need to honor principles of informed consent, be aware of power differences between ourselves and our patients, be certain that our counseling is not coercive, and carefully respect our patients’ choices.

Previously: Research supports IUD use for teens, Will more women begin opting for an IUD?, Study shows women may overestimate the effectiveness of common contraceptives and Study: IUDs are a good contraceptive option for teens
Photo by Liz Henry

In the News, Medicine and Society, Nutrition, Parenting, Research, Women's Health

Research elaborates on how moms can protect their daughters’ body image

Research elaborates on how moms can protect their daughters' body image

6945839301_9d61091329_zIt’s been my experience that women struggle with their body image at some point on the way from girlhood to womanhood – this may be brief and exploratory, or get tangled with eating disorders and other destructive behaviors. When I had a period of bulimia in my early 20s, I reflected on (among other things) my mother’s relationship with food and body image, and so some new research from Ben-Gurion University in Israel struck a chord.

Maia Maor, PhD, a sociologist, and Julie Cwikel, PhD, a professor of social work and director of the Center for Women’s Health Studies and Promotion, invited adult mother-daughter pairs to reflect on various strategies the mothers used to instill resilience about body image in their daughters. The researchers identified five methods commonly used to resist or reject negative and oppressive messages about body image:

  1. Filtering: being cautious and sensitive regarding body image issues 
  2. Transmitting awareness of the dangers of eating disorders, which can cause illness and death
  3. Positive reinforcement, using affirmative language in regard to their daughters’ bodies
  4. Discussion: providing tools for criticism of dominant body-related messages
  5. Positivity: shifting the focus of food and body-related discussions away from weight loss and towards health and taking pleasure in food. 

In a press release from last week, Maor explained that “the focus on protective strategies was intended to achieve two goals: to emphasize the positive in mother-daughter relationships and to identify a repertoire of strategies available to parents and allied health professionals who wish to help their daughters or young women build a stable, positive body image.”

Feelings about food and bodies have long chains of intergenerational transmission. According to the release, “some of the mothers in the study recalled how their own mothers’ negative comments to them about eating too much led them to associate food with guilt and bad feelings. They raised their own daughters by instead talking about the quality of food, importance of food choices and its relationship to developing respect for their own bodies.”

The study appears in the journal Feminism & Psychology.

Previously: Incorporating the family in helping teens overcome eating disorders, Stanford study investigates how to prevent moms from passing on their eating disorders, Promoting healthy eating and a positive body image on college campuses, What a teenager wishes her parents knew about eating disorders, and Social website shown to boost teen girls’ body image
Photo by Thanasus Anastasiou

Clinical Trials, Health Disparities, Mental Health, Research, Stanford News

How people with mental illness get left out of medical research studies

How people with mental illness get left out of medical research studies

One of the enduring challenges of evidence-based medicine is that the characteristics of people who participate in clinical trials can differ markedly from those of patients who ultimately access the treatment which the trial evaluates. One of the many reasons this occurs is that researchers often exclude patients with certain characteristics from participating in clinical trials.  In a new study in Journal of Psychiatric Research, my colleagues Laura Roberts, MD; Janet Blodgett, and I examine a particular population to whom this occurs: People with mental health and/or substance use disorders.

If scientists are to live up to their laudable commitment to sharing the benefits of health research with all citizens, they’ll have to more consistently include people with psychiatric problems in studies

In a sample of 400 highly-cited randomized trials across 20 common chronic disorders, we found that half had eligibility rules that prevented people with psychiatric problems from enrolling.   Those disease research areas with high rates of reported psychiatric exclusion criteria in clinical trials included low back pain (75 percent), osteoarthritis (57 percent), COPD (55 percent), and diabetes (55 percent).  People with conditions such as depression, anxiety disorders, alcohol problems and schizophrenia thus may face some added risk when they seek health care: People like them were often left out of the research that tells doctors what medical treatments work.

The study also raises questions about whether some clinical trials make much of a contribution to knowledge. For example, now that psychiatric and other substance use problems are virtually normative among smokers, what is the point of smoking cessation studies that continue to exclude the very populations that do most of the smoking?

Including people with psychiatric problems in medical research may require extra resources for researchers (e.g., people with serious mental illness may be harder to follow up) or pose other challenges in completing clinical trials. But if scientists are to live up to their laudable commitment to sharing the benefits of health research with all citizens, they’ll have to meet these challenges and more consistently include people with psychiatric problems in medical research studies.

Addiction expert Keith Humphreys, PhD, is a professor of psychiatry and behavioral sciences at Stanford and a career research scientist at the Palo Alto VA. He has served in the past as a senior advisor in the Office of National Drug Control Policy in Washington, DC. He can be followed on Twitter at @KeithNHumphreys.

Autoimmune Disease, Chronic Disease, FDA, Immunology, Pediatrics, Research, Stanford News

Can a safe, cheap pill prevent type 1 diabetes?

Can a safe, cheap pill prevent type 1 diabetes?

happy pillType 1 diabetes, an autoimmune disorder once known as juvenile diabetes because it tends to strike during adolescence or earlier, affects one in every 300 people. With the diagnosis comes the certainty of a lifetime of insulin injections, made necessary due to the destruction of insulin-producing cells in the pancreas by a misguided immune system.

Insulin is a hormone that alerts the body to the presence of glucose in the blood, typically after a meal. In insulin’s absence, the body’s tissues fail to take up glucose, a key energy source. Without several-times-daily insulin shots, type 1 diabetes patients’ blood sugar levels can shoot up to dangerous heights – a condition called hyperglycemia.

There’s never been any way to prevent type 1 diabetes, although it can be predicted based on the detection of self-targeting antibodies in a blood test. But screening for type 1 diabetes this way hasn’t been particularly useful, because there’s been nothing to be done for patients diagnosed in the asymptomatic phase except wait for them to become hyperglycemic and put them on insulin.

Now, an elaborate mouse study by Stanford immunologist and structural biologist Paul Bollyky, MD, PhD, shows that it might be possible to intervene during the asymptomatic stage of type 1 diabetes – using a pharmaceutical compound that’s been on the global market for more than 40 years and has a terrific safety record – thereby stopping the immune system’s stupid but relentless destruction of the pancreas’s vital insulin-producing cells, and stave off hyperglycemia indefinitely.

Bollyky and his colleagues first showed that a particular substance, hyaluronan, builds up near insulin-producing cells in mice developing the murine equivalent of type 1 diabetes, confirming earlier findings in postmortem human pancreatic tissue that had been supplied to Bollyky’s team by the Juvenile Diabetes Research Foundation.

“We wondered what would happen if we prevented that buildup,” Bollyky told me when I interviewed him for my news release on the study. “And we knew a drug that does that.”

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