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Applied Biotechnology, Clinical Trials, FDA, Research, Stanford News

An inside look at drug development

An inside look at drug development

B0008664 Assorted pills, tablets and capsules

How are drugs born? If you’re really curious about this, you’d be fascinated by the weekly meetings of industry experts and academic researchers taking part in Stanford’s drug-development training program known as SPARK.

A recently published book, A Practical Guide to Drug Development in Academia, crystallizes the sessions. Even if you’re not a scientist dreaming of curing cancer with your latest discovery, you might find it interesting.

In his recent review of the book for Nature Chemical Biology, industrial medicinal chemist Derek Lowe, PhD, writes:

I would actually welcome it if this book’s intended audience were broadened even more. Younger scientists starting out in the drug industry would benefit from reading it and getting some early exposure to parts of the process that they’ll eventually have to understand. Journalists covering the industry (especially the small startup companies) will find this book a good reality check for many an over-hopeful press release. Even advanced investors who might want to know what really happens in the labs will find information here that might otherwise be difficult to track down in such a concentrated form.

Lowe also wrote about the book last week on his blog, In the Pipeline, where an interesting discussion has begun.

Previously: SPARK program helps researchers cross the “valley of death” between drug discovery and development and Accelerating the translation of biomedical research into clinical applications.
Photograph from Wellcome Images

Aging, Applied Biotechnology, Biomed Bites, Research, Science, Videos

Are your cells stressed out? One Stanford researcher is helping them relax

Are your cells stressed out? One Stanford researcher is helping them relax

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers. 

In her family, Daria Mochly-Rosen, PhD, is the odd woman out: One parent and four of her siblings are architects.

But as the George D. Smith Professor in Translational Medicine at Stanford, Mochly-Rosen brings her family’s focus on space and design to her work as a biomedical researcher. “I’m looking at the cell as a physical space as a room or a building where things need to touch each other in certain ways,” Mochly-Rosen says in the video above.

She applies this lens of the world to address several basic research questions, including learning about how cells deal with stress. For a cell, stress isn’t a bad day at work or a rough commute home. Instead, its prolonged exposure to chemicals or physical forces that build up and impair cellular function.

In healthy cells, there are “lots of little machines” that reduce the stress, Mochly-Rosen said. In her lab, researchers work to enhance the efficacy of these built-in destressors and to capitalize on the cell’s existing machinery. She says:

We are really interested in finding ways to boost them up and to increase their activity so we can deal better with stresses that are associated with disease or even with simple aging.

And what we do there is we try to find small molecules — in other words, drugs — that will boost the system.

For example, Mochly-Rosen and her team have discovered a molecule that helps with the negative effects of alcohol and alcohol-related cancers.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Why drug development is time consuming and expensive (hint: it’s hard), New painkiller could tackle pain, without risk of addiction and Stanford researchers show how hijacking an enzyme could help reduce cancer risk

Applied Biotechnology, Cancer, Evolution, Immunology, Research, Stanford News

Corrective braces adjust cell-surface molecules’ positions, fix defective activities within cells

Corrective braces adjust cell-surface molecules' positions, fix defective activities within cells

bracesStanford molecular and cellular physiologist and structural biologist Chris Garcia, PhD, and his fellow scientists have tweaked together a set of molecular tools that work like braces of varying lengths and torque to fix things several orders of magnitude too small to see with the naked eye.

Like faulty cell-surface receptors, for instance, whose aberrant signaling can cause all kinds of medical problems, including cancer.

Cell-surface receptors transmit naturally occurring signals from outside cells to the insides of cells. Molecular messengers circulating in the blood stumble on receptors for which they’re a good fit, bind to them, and accelerate or diminish particular internal activities of cells, allowing the body to adjust to the needs of the minute.

Things sometimes go wrong. One or another of the body’s various circulating molecular messengers (for example, regulatory proteins called cytokines) may be too abundant or scarce. Alternatively, a genetic mutation may render a particular receptor type overly sluggish, or too efficient. One such mutation causes receptors for erythropoietin – a cytokine that stimulates production of certain blood-cell types – to be in constant overdrive, resulting in myeloproliferative disorders. Existing drugs for this condition sometimes overshoot, bringing the generation of needed blood-cell types to a screeching halt.

Garcia’s team took advantage of the fact that many receptors – erythropoietin receptors, for example – don’t perform solo, but instead work in pairs. In a proof-of-principle study in Cell, Garcia and his colleagues made brace-like molecular tools composed of stitched-together antibody fragments (known in the trade as diabodies). They then showed that these “two-headed beasts” can selectively grab on to two members of a mutated receptor pair and force the amped-up erythropoietin receptors into positions just far enough apart from, and at just the right angles to, one another to slow down their hyperactive signaling and act like normal ones.

That’s a whole new kind of therapeutic approach. Call it “cellular orthopedics.”

Previously: Souped-up super-version of IL-2 offers promise in cancer treatment and Minuscule DNA ring tricks tumors into revealing their presence
Photo by Zoe

Applied Biotechnology, Bioengineering, Medical Education, Stanford News, Videos

An online film festival for medtech inventors

An online film festival for medtech inventors

biodesign-process

The Stanford Biodesign program recently posted 296 short education videos on medical technology innovation. From needs finding through business planning, it offers entrepreneurs hours of useful advice on developing medical products.

This video library, which was launched with the second edition of the Biodesign textbook, is free to all. Its well-designed online interface makes it easy to access the advice that medtech innovators need, when they need it.

To create the video library, Biodesign hired filmmakers from both inside and outside of Stanford to capture the essence of the 2013-14 Biodesign fellowship program. During this ten-month program, multidisciplinary teams undergo a process of sourcing clinical needs, inventing solutions and planning for implementation of a business strategy. The program’s track record for bringing new medical devices and technologies to patients is impressive: Biodesign fellows have founded more than 30 companies in the last 14 years.

Each three- to four-minute video features interviews with faculty, fellows, CEOs, investors and alumni who have gone on to launch companies. A few of my favorites are:

The Biodesign video library, which was supported by the Walter H. Coulter Foundation, is an extension of the program’s mission — to help train the next generation of leaders in biomedical technology innovation. While the Stanford-based Biodesign program admits only 12 full-time postgraduate fellows a year, now these lessons-learned can be shared with medtech entrepreneurs around the globe. Just B.Y.O.P. (Bring your own popcorn.)

Previously: A medical invention that brings tears to your eyesBiodesign fellows take on night terrors in children, Stanford Biodesign Program releases video series on the FDA systemHeart devices get at mobile makeover
Illustration from Cambridge University Press

Applied Biotechnology, Bioengineering, Cancer, Genetics, Research, Stanford News

Minuscule DNA ring tricks tumors into revealing their presence

Minuscule DNA ring tricks tumors into revealing their presence

cool minicirclesAn animal study just published in Proceedings of the National Academy of Sciences shows how, in the not-distant future, doctors may be able to not only detect tumors early in humans, but also monitor the effectiveness of cancer drugs in real time, guide clinical trials of new drugs, and even screen entire populations of symptom-free people for nascent tumors that could have otherwise slipped under the radar.

The potential is huge. And the principal investigator, Sam Gambhir, MD, PhD, is credible: He chairs Stanford’s radiology department, directs the Canary Center at Stanford for Cancer Early Detection and has authored or co-authored nearly 600 peer-reviewed research publications.

From my news release about the study:

Imagine: You pop a pill into your mouth and swallow it. It dissolves, releasing tiny particles that are absorbed and cause only cancerous cells to secrete a specific protein into your bloodstream. Two days from now, a finger-prick blood sample will expose whether you’ve got cancer and even give a rough idea of its extent. That’s a highly futuristic concept. But its realization may be only years, not decades, away.

The key to early cancer detection lies in finding valid biomarkers: substances whose presence in a person’s blood or urine flags a probable tumor. (High blood levels of the molecule known as PSA, for example, can signify prostate cancer.) But although various tumor types indeed secrete characteristic substances into the blood, these same substances typically are made in healthy tissues, too, albeit usually in smaller amounts. So a positive test result for, say, PSA doesn’t necessarily mean the person has cancer. Contrariwise, a small tumor just may not secrete enough of the trademark substance to be detectable.

Gambhir’s team appears to have found a way to force any of numerous tumor types to produce a biomarker whose presence in the blood unambiguously signifies cancer, because no adult tissues – cancerous or otherwise – would normally be making it. This particular substance is a protein naturally present in human embryos as they’re forming and developing, but absent in adults.

The scientists designed a genetic construct, called a DNA minicircle, that contains a single gene coding for the telltale substance. DNA minicircles are tiny, artificial, single-stranded DNA rings about 4,000 nucleotides in circumference – roughly one-millionth as long as the strand that you’d get if you stretched the DNA in all 23 chromosomes of the human genome end to end.

Gambhir and his colleagues rigged their minicircles so that this sole gene would be “turned on” only inside cancer cells. (For more details on how to do this, please see my release.) They injected the minicircles into mice who had small tumors and mice who didn’t. Within 48 hours, a simple blood test indicated the presence of the biomarker in the blood of mice with tumors, but not in the blood of the tumor-free mice.The bigger the tumor volume, the more of the biomarker in the blood.

The technique will likely apply to a broad range of cancers, and can possibly be modified to help pinpoint budding tumors’ location in the body.

Previously: Nano-hitchhikers ride stem cells into heart, let researchers watch in real time and weeks later, Nanoparticles home in on human tumors growing in mice’s brains, increase accuracy of surgical removal and Nanomedicine moves one step closer to reality
Photo by Jim Strommer

Applied Biotechnology, Stanford News, Technology

Stanford team produces free Braille notetaker app

Stanford team produces free Braille notetaker app

brailleIn 2011, we showed you a video demonstration of an app that enables visually impaired people to type on a touchscreen tablet. Over the past few years, Sohan Dharmaraja, PhD, and Adrian Lew, PhD, completely redesigned the prototype they first developed with New Mexico State University student Adam Duran at Stanford’s Army High-Performance Computing Research Center. Now, their app, called iBrailler Notes, is ready for prime time.

This finished product, as Dharmajara and Lew explain in a recent story in Stanford Report, looks nothing like the original prototype that caught the media’s eye over three years ago. “Creating a prototype is relatively easy when your audience is a handful of fellow classmates. We did it almost as a whim to see if we could do it,” Dharmaraja said. “But creating a real app, that potentially millions might rely upon every day, is a whole other ballgame.”

Redesigning the app was no small feat because the final design had to be intuitive for users that may have little to no experience with touchscreen technology. As Dharmaraja explains, several of their test subjects had never used a tablet before:

Our testers did not know what a tablet computer or a touchscreen was, much less how to use them. We had to teach them how to use a touchscreen before they could tell us how to improve our products.

Dharmajara and Lew patterned their iBrailler Notes app after the traditional eight-keyed Perkins Brailler. What makes iBrailler Notes unique is the app enables the user to type regardless of where they position their fingers on the touchscreen—the user simply places eight to ten fingers on the touchscreen and the app automatically encircles each fingertip with a key. More from the article:

“We constantly pushed ourselves to innovate because being born with a disability shouldn’t mean you get left out of today’s technology revolution,” Dharmaraja said. “When you see the smile of someone doing something that you and I take for granted, it’s motivating.”

Lew added, “We think the time was well-spent to get it right.”

Previously: Developing a touchscreen Braille writerTennis, anyone? New York Times examines tennis for the blindMap of the Carina Nebula for the visually impairedRubik’s Cube for the visually impairedThe blind can see, and The mind maps the visual world with minimal means.
Photo courtesy of Sohan Dharmaraja

Applied Biotechnology, In the News, Patient Care, Technology

Building bodies, one organ at a time

Building bodies, one organ at a time

bioprinting muscle. jpg

If you’ve been to a geek or tech event like the annual Maker Faire that happens every spring here in the Bay Area, you’ve probably seen demonstrations of 3D printers that can spit out toys or jewelry.

What’s really interesting is how researchers and doctors are harnessing that technology to help their patients by making prosthetics for amputated arms, or replacements parts for damaged bones. A recent article in the San Jose Mercury News highlights this new frontier and features Stanford cardiologist Paul Wang, MD, who describes one of the biggest advantages of 3D printing:

“You can make things for tens of dollars rather than thousands of dollars,” said Stanford University professor Dr. Paul Wang, a cardiovascular and bioengineering expert who is among those studying the printers’ potential for prosthetics, replacement bones and other applications. “It’s totally opened up what’s possible.”

Printing prosthetics or bone substitutes using inorganic materials is just the beginning of how scientists hope to use 3D printing; many are trying to use the technology to print living tissue and organs. Doing so is a challenging endeavor – for starters, even relatively simple organs need networks of blood vessels that can constantly feed its cells – but several research teams are betting they can solve the puzzle:

University of Pennsylvania researchers say they’ve designed a way to print those [blood vessel] networks and a Russian company, 3D Bioprinting Solutions, has vowed this year to 3D-print a transplantable thyroid gland, which is laced with blood vessels.

Still other researchers are 3D-printing insulin-producing pancreatic tissues to help manage diabetes, viruses that can attack cancer cells and organ models that surgeons can practice on or that can be used to help design medical devices.

Stanford’s Wang, for example, has made a 3D-printed model of the heart along with a prototype of a tiny gadget he envisions one day could crawl though real hearts to gather information on the organ’s health or kill cells that damage it.

The field has the potential to be a financial windfall for companies that can bring a viable medical product to market, but one of the biggest hurdles is the regulatory process, which can stretch out over a decade or more for new devices. Still, as detailed in the article, proponents are “encouraged by the impact 3D printing already is having on health care” and remain optimistic about the future.

Previously: Countdown to Medicine X: 3D printing takes shapeCreating organ models using 3D printing3D printer in China makes tiny ear and 3D printer uses living cells to produce a human kidney
Photo of researcher printing muscle tissue by U.S. Army Materiel Command

Applied Biotechnology, Biomed Bites, Genetics, History, Research, Videos

Basic research underlies effort to thwart “greatest threat to face humanity”

Basic research underlies effort to thwart "greatest threat to face humanity"

Welcome to this week’s Biomed Bites, a weekly feature that introduces readers to Stanford’s most innovative researchers. 

Stanley Cohen, MD, isn’t a household name. But it probably should be. The Stanford geneticist was instrumental in the discovery of DNA cloning – the technology that underlies innumerable advances in biotechnology and medicine, and led to the founding of biotech giant Genentech.

It wasn’t always thought possible to snip out a gene, stitch it into a new stretch of DNA – often in a different organism – and have it produce a desired protein.

In the video above, Cohen emphasizes that striving to achieve a concrete – and profitable – goal didn’t enable the discovery of gene cloning. First, researchers had to work to understand the basic biological processes. “In order to apply knowledge, it’s necessary to get that knowledge somehow.”

These days, Cohen isn’t resting on his laurels. Instead, he’s striving to thwart what he considers perhaps the “greatest threat to humanity,” drug-resistent microbes.

“My lab is still interested in understanding microbial drug resistance and the way in which microbes exploit host genes to carry out microbial functions such as entering cells, reproducing in cells and exiting from cells,” he said. Scientists need that basic knowledge to develop strategies to thwart the process, he added.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: The history of biotech in seven bite-sized chunks, The dawn of DNA cloning: Reflections on the 40th anniversary and Why basic research is the venture capital of the biomedical world

Applied Biotechnology, Bioengineering, Ophthalmology, Stanford News, Videos

A medical invention that brings tears to your eyes

A medical invention that brings tears to your eyes

dry-eye-implantMore than 20 million Americans suffer from dry eye, a painful condition where a personal’s lacrimal glands don’t create enough tears to lubricate the surface of the eye.

But relief is around the corner for these sufferers – a tiny implantable device that stimulates natural tear production on a long-term basis is currently in clinical trials. The device increases tear volume by delivering micro-electrical pulses to the lacrimal gland. It’s inserted into the mucus lining of the sinus cavity or under the skin beneath the eyebrow. Tear delivery rates can be adjusted manually with a wireless controller. (You can watch a video of this device producing tears, below.)

This clever invention is the brainchild of bioengineer and former Stanford Biodesign fellow Michael Ackermann, PhD, who says he spent a good part of his boyhood in Louisville, Kentucky, taking apart things like VCRs, radios and weed-whackers.

“My parents wanted me to be a doctor, but it was very clear from a young age that I was going to be an engineer,” said Ackermann.

He’s now at the helm of Oculeve, a 20-person startup dedicated to helping people with dry-eye. Ackermann’s tale of how he took one crazy idea and turned it into a product that has the potential to help millions of people is featured in the latest issue of Inside Stanford Medicine.

More than one person’s story, it’s another example of the efficacy of the Stanford Biodesign training program, whose fellows have started 36 medtech companies and filed more than 200 patents, all of which have reached 250,000-plus patients.

Previously: Crying without tears unlocks the mystery of a new genetic disease, Instagram for eyes: Stanford ophthalmologists develop low-cost device to ease image sharing and Stanford-developed eye implant could work with smartphone to improve glaucoma treatments
Photo and video by Michael Ackermann

Applied Biotechnology, Bioengineering, Biomed Bites, Cancer, Imaging, Technology, Videos

Beam me up! Detecting disease with non-invasive technology

Beam me up! Detecting disease with non-invasive technology

Here’s this week’s Biomed Bites, a feature appearing each Thursday that introduces readers to Stanford’s most innovative biomedical researchers.

Star Trek fans rejoice! Stanford radiologist Sam Gambhir, MD, PhD, hopes that someday he’ll be able to scan patients using a handheld device — similar to the one used by Bones in the popular sci-fi series — to check their health.

“Our long-term goals are to be able to figure out what’s going on in each and every one of you cells anywhere in your body by essentially scanning you,” Gambhir said in the video above. “We’ve been working on this area for well over three decades.”

This is useful because it will help doctors diagnose diseases such as cancer months or even years before the symptoms become apparent, Gambhir said.

And these advances aren’t light-years away. “Many of the things we’re doing have already started to move into the hospital setting and are being tested in patients. Many others will come in the years to follow,” he said.

Gambhir is chair of the Department of Radiology. He also directs the Molecular Imaging Program and the Canary Center for Cancer Early Detection.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Stanford partnering with Google [x] and Duke to better understand the human body, Nano-hitchhikers ride stem cells into heart, let researchers watch in real time and weeks later and Developing a new molecular imaging system and technique for early disease detection

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