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Clinical Trials, Research, Science, Stanford News

SPARK program helps researchers cross the “valley of death” between drug discovery and development

SPARK program helps researchers cross the “valley of death” between drug discovery and development

Mochly-RosenSeveral years ago, Stanford neuroscientist Craig Garner, PhD, found himself facing a common problem for researchers: figuring out how to cross the so-called “valley of death” between drug discovery and development. In his case, he wanted to get pharmaceutical companies interested in funding his lab’s promising new Down syndrome treatment.

The answer was SPARK, a hands-on training program that assists scientists in moving their discoveries from bench to bedside. The program was created by Daria Mochly-Rosen, PhD, after she experienced challenges in getting her own entrepreneurial venture off the ground. A story published in yesterday’s Inside Stanford Medicine explains how Mochly-Rosen and a group of industry experts search hundreds of patents submitted to the university’s Office of Technology Licensing and select projects, such as Garner’s, that could benefit from SPARK’s help. My colleague Ranjini Raghunath writes:

Since SPARK’S founding, 51 research teams have “graduated” from the program. More than half of its projects have been licensed or have advanced to clinical use, or both, in sharp contrast to the pharmaceutical industry’s own success rate of approximately five percent. With SPARK’s support, a research team led by dermatologist Alfred Lane, MD, has received a fund- able score on a food and Drug Administration orphan grant for phase-2 trials of a repurposed drug to treat lymphatic malformations that disfigure and disable children. Another team, led by immunologists William Robinson, MD, PhD, and Jeremy Sokolove, MD, is testing a combination of drugs to treat early stages of cartilage loss and joint degeneration in bone arthritis. findings of a third research team led by bioinformatics expert Atul Butte, MD, PhD, and Bruce Ling, PhD — biomarkers for detecting dangerously high blood pres- sure in pregnancy — have already been picked up for licensing by a start-up biotechnology company. Former SPARK beneficiaries, or “SPARKees,” have credited the program with helping them get research grants, publish papers in reputable journals and even land a tenure-track position, Mochly-Rosen said.

The piece goes on to note that universities around the world have launched, or are developing, their own SPARK programs. Mochly-Rosen’s overall goal for the program is to integrate Stanford and other institutions’ programs under one brand and use it to attract commercial investors to support early-stage research discoveries.

Previously: Director of NIH discusses accelerating translation of biomedical research into clinical applications, Re-engineering the drug-development process to speed medical advances, Why drug development is time consuming and expensive (hint: it’s hard) and A glimpse at the price of drugs: Why they cost what they cost
Photo of Daria Mochly-Rosen by Steve Gladfelter

Addiction, Behavioral Science, In the News, Mental Health, Research

Knitting as ritual – with potential health benefits?

Knitting as ritual - with potential health benefits?

knittingDuring finals, one of my college roommates would ritualistically sit in silence and knit an entire hat before she could begin studying. The steady, repetitive action calmed her down and cleared her mind. (Before less stressful exams, she baked.)

I thought of her when coming across a recent post on The Checkup that points to evidence, including previous research in seniors with mild cognitive impairment, that the health benefits experienced by people who engage in activities such as knitting and crocheting might be more than anecdotal. More from the piece:

In one study, 38 women hospitalized for anorexia were given a questionnaire about their psychological state after being taught to knit.

After an average of one hour and 20 minutes of knitting a day for an average of three weeks, 74 percent of them reported less fear and preoccupation with their eating disorder, the same percentage reported that knitting had a calming effect, and just over half said knitting gave them a sense of pride, satisfaction and accomplishment.

The rhythmic movements of knitting offer many of the same kinds of benefits as meditation, says Carrie Barron, [MD,] an assistant clinical professor of psychiatry at Columbia University in New York and co-author of the book “The Creativity Cure: How to Build Happiness With Your Own Two Hands.” In addition, she says, seeing a project take shape provides a deep sense of satisfaction.

That might have been why Pee-wee Herman found the unsolved mystery of his stolen bike so unnerving: “It’s like you’re unraveling a big cable-knit sweater that someone keeps knitting and knitting and knitting…” he said in the 1985 film Pee Wee’s Big Adventure.

Previously: Image of the Week: Personalized brain activity scarves, Image of the Week: aKNITomy, Study shows meditation may alter areas of the brain associated with psychiatric disorders and Ommmmm… Mindfulness therapy appears to help prevent depression relapse
Photo by Merete Veian

Bioengineering, In the News, Neuroscience, Stanford News, Technology

New York Times profiles Stanford’s Karl Deisseroth and his work in optogenetics

New York Times profiles Stanford's Karl Deisseroth and his work in optogenetics

Rockefeller University neurobiologist Cori Bargmann, PhD, is quoted in today’s New York Times as saying optogenetics is “the most revolutionary thing that has happened in neuroscience in the past couple of decades.” The article is a profile piece of Karl Deisseroth, MD, PhD, the Stanford researcher who helped create the field of optogenetics, and it reveals how a clinical rotation in psychiatry led him to this line of work:

It was eye-opening, he said, “to sit and talk to a person whose reality is different from yours” — to be face to face with the effects of bipolar disorder, “exuberance, charisma, love of life, and yet, how destructive”; of depression, “crushing — it can’t be reasoned with”; of an eating disorder literally killing a young, intelligent person, “as if there’s a conceptual cancer in the brain.”

He saw patient after patient suffering terribly, with no cure in sight. “It was not as if we had the right tools or the right understanding.” But, he said, that such tools were desperately needed made it more interesting to him as a specialty. He stayed with psychiatry, but adjusted his research course, getting in on the ground floor in a new bioengineering department at Stanford. He is now a professor of both bioengineering and psychiatry.

Previously: A federal push to further brain research, An in-depth look at the career of Stanford’s Karl Deisseroth, “a major name in science”, Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, The “rock star” work of Stanford’s Karl Deisseroth and Nature Methods names optogenetics its “Method of the Year
Related: Head lights
Photo in featured-entry box by Linda Cicero/Stanford News Service

Neuroscience, Research, Stanford News

Thoughts light up with new Stanford-designed tool for studying the brain

Thoughts light up with new Stanford-designed tool for studying the brain

A 3d rendered illustration of a nerve cell.

When I talk to neuroscientists about how they study the brain I get a lesson (usually filled with acronyms) in the various ways scientists go about trying to read minds. Some of the tools they use can detect when general regions of the brain are active, but can’t detect individual nerves. Others record the activity of individual nerves, one nerve at a time, but can’t detect networks of nerves firing together. Still another tool can report the afterglow of a signal that has been sent across networks of neurons.

There hasn’t been any one way of seeing when a nerve fires and which neighbors in connects to.

I wrote recently about a new tool to do just that, developed by bioengineer Michael Lin, MD, PhD, and biologist and applied physicist Mark Schnitzer, PhD. They’ve both come up with proteins that light up when a nerve sends a signal. They can put their proteins in a group of nerves in one part of the brain then watch those signals spread across the network of neurons as they interact.

In my story I quote Lin: “You want to know which neurons are firing, how they link together and how they represent information. A good probe to do that has been on the wish list for decades.”

The proteins could be widely used to better understand the brain or develop drugs:

With these tools scientists can study how we learn, remember, navigate or any other activity that requires networks of nerves working together. The tools can also help scientists understand what happens when those processes don’t work properly, as in Alzheimer’s or Parkinson’s diseases, or other disorders of the brain.

The proteins could also be inserted in neurons in a lab dish. Scientists developing drugs, for example, could expose human nerves in a dish to a drug and watch in real time to see if the drug changes the way the nerve fires. If those neurons in the dish represent a disease, like Parkinson’s disease, a scientist could look for drugs that cause those cells to fire more normally.

Now that I’ve written about the invention of this new tool I’m looking forward to hearing more about how scientists start using it to understand our brain or develop drugs.

3D rendered illustration of a nerve cell by Sebastian Kaulitzki/Shutterstock

Cancer, Research, Science, Stanford News, Stem Cells

Cellular culprit identified for invasive bladder cancer, according to Stanford study

Cellular culprit identified for invasive bladder cancer, according to Stanford study

Beachy image resizedInvasive bladder cancer is a grim disease that is expensive to treat and requires ongoing monitoring due to its high probability of recurrence. Stanford developmental biologist Philip Beachy, PhD, and urologist Michael Hsieh, MD, PhD, wanted to know how the cancer starts, and what makes it so intractable. Their research was published yesterday in Nature Cell Biology (subscription required).

As Beachy explained in the release I wrote:

We’ve learned that, at an intermediate stage during cancer progression, a single cancer stem cell and its progeny can quickly and completely replace the entire bladder lining. All of these cells have already taken several steps along the path to becoming an aggressive tumor. Thus, even when invasive carcinomas are successfully removed through surgery, this corrupted lining remains in place and has a high probability of progression.

In the photo above, the blue cells are progeny of just one cancer-initiating cell in the basal cell layer of the bladder lining. They’ve “elbowed out” their neighbors to take over the lining. The cells, and the cancers that arise, have a distinctive gene-expression profile. More from our release:

Although the cancer stem cells, and the precancerous lesions they form in the bladder lining, universally express an important signaling protein called sonic hedgehog, the cells of subsequent invasive cancers invariably do not — a critical switch that appears vital for invasion and metastasis. This switch may explain certain confusing aspects of previous studies on the cellular origins of bladder cancer in humans. It also pinpoints a possible weak link in cancer progression that could be targeted by therapies.

Hsieh, who has treated many patients with this type of bladder cancer, explained to me the significance of the finding:

This could be a game changer in terms of therapeutic and diagnostic approaches. Until now, it’s not been clear whether bladder cancers arise as the result of cancerous mutations in many cells in the bladder lining as the result of ongoing exposure to toxins excreted in the urine, or if it’s due instead to a defect in one cell or cell type. If we can better understand how bladder cancers begin and progress, we may be able to target the cancer stem cell, or to find molecular markers to enable earlier diagnosis and disease monitoring.

Previously: Is the worm turning? Early stages of schistosomiasis bladder infection charted, Mathematical technique used to identify bladder cancer marker and Bladder infections–How does your body repair the damage?
Photo by Kunyoo Shin, PhD

Global Health, HIV/AIDS, Research, Stanford News

Foreign aid for health extends life, saves children, Stanford study finds

Foreign aid for health extends life, saves children, Stanford study finds

Kenyan child pic - smallMany people are deeply skeptical of foreign aid, believing that these monies often wind up in the pockets of corrupt leaders or never make it down the chain of bureaucracy to the people who really need it. But a new Stanford analysis of both government and private aid programs shows that health aid has been extremely effective not only in extending the lives of people in developing countries but also saving the lives of children under age 5.

Lead researcher Eran Bendavid, MD, said foreign aid programs had their biggest impact between 2000 and 2010, when investments in health reached their peak. During that time, the U.S. government launched its hugely successful initiative, the President’s Emergency Plan for AIDS Relief (PEPFAR), while other private groups, such as the Gates Foundation, stepped up investments in health as well.

During that time, low-income countries receiving aid saw a dramatic decline – between 26 and 34 percent – in the number of children who died before their 5th birthday. With just a 4 percent increase in aid, or $1 billion, foreign aid could continue to have a major impact on child mortality, Bendavid said.

“If health aid continues to be as effective as it has been, we estimate there will be 364,800 fewer deaths in children under 5,” Bendavid said. “We are talking about $1 billion, which is a relatively small commitment for developed countries.”

He said many people may find the results surprising. “But for me, it fits with other evidence of the incredible success of public health promotion in developing countries,” he said. For instance, he did a study in 2012 which found that more than 740,000 lives were saved between 2004 and 2008 in nine countries as a result of the PEPFAR program. Other technologies, such as diphtheria, tetanus, measles and polio vaccines for children and insecticide-treated bed nets to prevent malaria, all have contributed to better health among adults and children in low-income countries.

He and colleague Jay Bhattacharya, MD, PhD, also found that aid programs had a lasting impact. The signs of aid’s impact on child mortality were measurable for three years after aid was distributed, while the link between aid and longer life expectancy was detectable five years after aid was made available, the researchers reported.

Previously: Stanford study: South Africa could save millions of lives through HIV prevention and PEPFAR has saved lives – and not just from HIV/AIDS, Stanford study finds
Photo by Karen Ande

Dermatology, Health Costs, In the News, Research, Stanford News, Videos

Stanford dermatologist tackles free drug samples on NewsHour

Stanford dermatologist tackles free drug samples on NewsHour

Last week, my colleague reported on a new Stanford study showing that free drug samples lead to more expensive prescriptions. Over the weekend, dermatologist Al Lane, MD, senior author of the study, appeared on PBS NewsHour to discuss the implications of his findings. (He’s also quoted in a New York Times blog post on the research.) After mentioning that pharmaceutical companies spend more than $6 billion a year on sampling, he told NewsHour’s Hari Sreenivasan “that [this] cost eventually has to be paid by someone.” And he closes on a powerful note:

One of the focuses of our study was for the dermatologists to realize that although they think they’re helping the patients, they’re really being manipulated to write for more expensive medications with no proven benefit of those medications over the generic drugs.

Previously: Drug samples lead to more expensive prescriptions, Stanford study finds

In the News, Nutrition, Public Health

Health initiatives at the White House gain popularity

Health initiatives at the White House gain popularity

Barack Obama, Michelle ObamaIn case you missed it, The Washington Post recently took a look at how the Obamas are bringing flavors of healthy eating and activity into their home. An article describes how a culture of health drives not only President and First Lady Obama, but also influences their family, members of the current administration and nation-wide initiatives.

From the piece:

Earlier this year, there was an intense battle for bragging rights inside the complex as teams of six with names such as “Runnin’ Like Amtrak,” from Vice President Biden’s staff, and “Team Engage (Our Core),” from the Office of Public Engagement, earned a point for every 30 minutes of “moderate-to-vigorous physical activity” performed each day. Each team totaled its points each week.

“The culture here has shifted pretty dramatically, in direct ways and indirect ways, based on their leadership,” said Sam Kass, executive director of first lady Michelle Obama’s Let’s Move initiative and the White House senior policy adviser for nutrition policy. “I think we really live that. I think that’s been a transformation for the kitchen

In Obamaworld, the methods staff members use to reach their diet and fitness goals reflect their faith in the power of technology and data. Council of Economic Advisers Chairman Jason Furman, [PhD,] who got kudos from the president after he lost 50 pounds, surveyed the scientific literature on weight loss, tracked his food consumption and rate of physical behavior electronically and converted it into a spreadsheet to analyze it properly.

Past presidents and presidential candidates have taken different stances on eating and exercise behavior; as the article notes, “the cultural shift has political consequences.”

Previously: Classroom cupcakes: Should “party foods” at schools be limited?, White House announces “Apps for Healthy Kids” winners and An edible forest grows in Richmond: Urban gardening program teaches kids about food, nutrition
Photo by ASSOCIATED PRESS

Aging, Genetics, Neuroscience, Podcasts, Research, Stanford News

The state of Alzheimer’s research: A conversation with Stanford neurologist Michael Greicius

The state of Alzheimer's research: A conversation with Stanford neurologist Michael Greicius

My colleague Bruce Goldman recently wrote an expansive blog entry and article based on research by Mike Greicius, MD, about how the ApoE4 variant doubles the risk of Alzheimer’s for women. I followed up Goldman’s pieces in a podcast with Greicius, who’s the medical director of the Stanford Center for Memory Disorders.

I began the conversation by asking about the state of research for Alzheimer’s: essentially, what do we know? As an aging baby boomer, I’m interested in the differences between normal, age-related cognitive decline versus cognitive declines that signal an emerging disease. Greicius said people tend to begin losing cognitive skills around middle age:

Every cognitive domain we can measure starts to decline around 40. Semantic knowledge – knowledge about the world – tends to stay pretty stable and even goes up a bit. Everything else… working memory, short term memory all tends to go down on this linear decline. The difference with something like Alzheimer’s is that the decline isn’t linear. It’s like you fall off a cliff.

Greicius’ most recent research looks at the certain increased Alzheimer’s risk ApoE4 confers on women. As described by Goldman:

Accessing two huge publicly available national databases, Greicius and his colleagues were able to amass medical records for some 8,000 people and show that initially healthy ApoE4-positive women were twice as likely to contract Alzheimer’s as their ApoE4-negative counterparts, while ApoE4-positive men’s risk for the syndrome was barely higher than that for ApoE-negative men.

In addition to the increased risk of Alzheimer’s for women with the ApoE4 variant, I asked Greicius how he advises patients coming into the clinic who ask about staving off memory loss. At this point, he concedes, effective traditional medication isn’t really at hand. “Far and away our strongest recommendations bear on things like lifestyle and particularly exercise,” he said. “We know, in this case from good animal models, that physical exercise, particularly aerobic exercise, helps brain cells do better and can stave-off various insults.” So remember, a heart smart diet along with aerobic exercise.

One last question for Greicius: What about those cognitive-memory games marketed to the elderly and touted as salves for memory loss – do they have any benefit? He’s riled now: “I get asked that all the time, and smoke starts coming out of my ears.” He says the games are nothing more than snake oil.  His advice when he gets asked the question: “Give that money to the Alzheimer’s Association or save it and get down on the floor with your grandkids and build Legos. That’s also a great cognitive exercise and more emotionally rewarding.”

Previously: Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women but not for men, Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s and Hormone therapy halts accelerated biological aging seen in women with Alzheimer’s genetic risk factor

Grand Roundup

Grand Roundup: Top posts for the week of April 13

The five most-read stories this week on Scope were:

Stanford bioengineer develops a 50-cent paper microscopeManu Prakash, PhD, assistant professor of bioengineering, has developed an ultra-low-cost paper microscope to aid disease diagnosis in developing regions. The device is further described in a technical paper.

A wake-up call from a young e-patient: “I need to be heard”: In this piece, 15-year-old Inspire contributor Morgan Gleason writes about living with the rare autoimmune disease juvenile dermatomyositis. A video about challenges she’s faced during her hospital stays has been widely shared.

Home videos could help diagnose autism, says new Stanford study: Short home videos, such as those posted on YouTube, may become a powerful tool for diagnosing autism, according to a new study from Dennis Wall, MD, associate professor of pediatrics in systems medicine.

Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women but not for men: A study led by Mike Greicius, MD, medical director of the Stanford Center for Memory Disorders, shows that carrying a copy of a gene variant called ApoE4 confers a substantially greater risk for Alzheimer’s disease on women than it does on men.

My fifth-year comeback: In the latest installment of SMS Unplugged, medical student Moises Gallegos reflects on the lessons, encounters and unforgettable moments he experienced during his clerkships.

And still going strong – the most popular post from the past:

Researchers explain how “cooling glove” can improve exercise recovery and performance: The “cooling glove,” a device that helps people cool themselves quickly by using their hand to dissipate heat, was created more than a decade ago by Stanford biologists Dennis Grahn and Craig Heller, PhD. This video demonstrates the device and explains how it can be used to dramatically improve exercise recovery and performance.

Stanford Medicine Resources: