Participants using a game-based app report benefits
Researchers have found promising results for treating depression with a video game interface that targets underlying cognitive issues associated with depression rather than just managing the symptoms.
“We found that moderately depressed people do better with apps like this because they address or treat correlates of depression,” said Patricia Areán, a UW Medicine researcher in psychiatry and behavioral sciences.
The first study enrolled older adults diagnosed with late-life depression into a treatment trial where they were randomized to receive either a mobile, tablet-based treatment technology developed by Akili Interactive Labs called Project: EVO or an in-person therapy technique known as problem-solving therapy (PST).
Project: EVO runs on phones and tablets and is designed to improve focus and attention at a basic neurological level. The results, published Jan. 3 in the journal Depression and Anxiety, showed that the group using Project: EVO demonstrated specific cognitive benefits (such as attention) compared to the behavioral therapy, and saw similar improvements in mood and self-reported function. Joaquin A. Anguera, a University of California, San Francisco (UCSF), researcher in neurology and psychiatry, is the lead author, and Areán is the senior author. The researchers have no commercial interests in the intervention manufactured by Akili Interactive Labs in Boston. The studies were funded by the National Institute of Mental Health.
“While EVO was not directly designed to treat depressive symptoms; we hypothesized that there may indeed be beneficial effects on these symptoms by improving cognitive issues with targeted treatment, and so far, the results are promising,” said Anguera.
People with late-life depression (60+) are known to have trouble focusing their attention on personal goals and report trouble concentrating because they are so distracted by their worries. Akili’s technology was designed to help people better focus their attention and to prevent people from being easily distracted.
Arean said most of the participants had never used a tablet, let alone played a video game, but compliance was more than 100 percent. The participants were required to play the game five times a week for 20 minutes, but many played it more. Participants in this arm of the study also attended weekly meetings with a clinician. The meetings served as a control for the fact that participants in the problem-solving therapy arm were seen in person on a weekly basis, and social contact of this nature can have a positive effect on mood.
A second study, which was another joint effort by UW and UCSF, randomized more than 600 people across the United States assessed as moderately or mildly depressed to one of three interventions: Akili’s Project: EVO; iPST, an app deployment of problem-solving therapy; or a placebo control (an app called Health Tips, which offered healthy suggestions).
Areán, the lead researcher on the study published Dec. 20 in the Journal of Medical Internet Research (JIMR), found that people who were mildly depressed were able to see improvements in all three groups, including the placebo. However, those individuals who were more than mildly depressed showed a greater improvement of their symptoms following their use of Project EVO or iPST versus the placebo.
Areán said much of her research is aimed at providing effective treatment to people who need it, and these results provide great potential for helping people who don’t have the resources to access effective problem solving therapy. But, she stressed, the apps should be used under clinical supervision because without a human interface, people were not as motivated to use it. In the JIMR study, 58 percent of participants did not download the app.
Akili’s technologies are based on a proprietary neuroscience approach developed to target specific neurological systems through sensory and digital mechanics. The company’s technology platform used in this trial is based on cognitive science exclusively licensed from the lab of Dr. Adam Gazzaley at UCSF, and adaptive algorithms developed at Akili, which are built into action video game interfaces. The technology targets an individual’s core neurological ability to process multiple streams of information.
Project: EVO is undergoing multiple clinical trials for use in cognitive disorders — including Alzheimer’s disease, traumatic brain injury and pediatric attention deficit hyperactivity disorder (ADHD), and the company is on path for potential FDA clearance to treat pediatric ADHD.
University of California, San Francisco research articles from Innovation Toronto
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- Animal Cells Can Communicate by Reaching Out and Touching, UCSF Team Discovers
- UC San Francisco hospital integrating robotic pharmacy
- A New Wrinkle in Parkinson’s Disease Research
- New Approach to Treating Venomous Snakebites Could Reduce Global Fatalities
- Epilepsy Cured in Mice Using Brain Cells
- Laser Light Zaps Away Cocaine Addiction
- United Nations Panel Calls Hormone Disruptors a “Global Threat”
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- Virtual Colonoscopy Without Laxative Equals Standard OC in Identifying Clinically Significant Polyps
- Computer Model Successfully Predicts Drug Side Effects
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- White House Petitioned to Make Research Free to Access
- Research Unveils Drug Against Entamoeba Hisotolica
- Can Computers Catch You Telling a Lie?
- Building Bone from Cartilage
- New ‘Biopsy in a Blood Test’ to Detect Cancer
- Researchers unveil prototype implantable artificial kidney to replace dialysis
- Disappearance of Coral Reefs, Drastically Altered Marine Food Web on the Horizon
- New Breakthrough Prize Awards Millions to Life Scientists
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- Scientists Decode Brain Waves to Eavesdrop On What We Hear
- Scientist Converts Human Skin Cells Into Functional Brain Cells
- Citizen Scientists and Social Media Aim to Help Prevent Frog Extinctions
- Getting Computers to Understand Overlapping Speech
- Ant Harm: Can Genetic Weapons Roll Back the Expansion of Argentine Ant Supercolonies?
- Forging a Hot Link to the Farmer Who Grows the Food
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- The Long Shot
UCSF is widely regarded as one of the world’s leading universities in health sciences. Though one of the 10 campuses of the University of California, it is unique for being the only University of California campus dedicated solely to graduate education, and in health and biomedical sciences. Some of UCSF’s treatment centers include kidney transplants and liver transplantation, radiology, neurosurgery, neurology, oncology, ophthalmology, gene therapy, women’s health, fetal surgery, pediatrics, and internal medicine.
Founded in 1873, the mission of UCSF is to serve as a “public university dedicated to saving lives and improving health.” The UCSF Medical Center is consistently ranked among the top 10 hospitals in the United States by U.S. News & World Report, who also ranked UCSF’s medical school as one of the top 10 in a number of specialties, including a specialty program in AIDS medical care ranked first in the country.
Inhibition of Molecular Pathway Lets Mouse Blastocysts Survive for Weeks in the Lab
UC San Francisco researchers have found a way to pause the development of early mouse embryos for up to a month in the lab, a finding with potential implications for assisted reproduction, regenerative medicine, aging and even cancer, the authors say.
The new study — published online Nov. 23, 2016, in Nature – involved experiments with pre-implantation mouse embryos, called blastocysts. The researchers found that drugs that inhibit the activity a master regulator of cell growth called mTOR can put these early embryos into a stable and reversible state of suspended animation.
“Normally, blastocysts only last a day or two, max, in the lab. But blastocysts treated with mTOR inhibitors could survive up to four weeks,” said the study’s lead author, Aydan Bulut-Karslioglu, PhD, a postdoctoral researcher in the lab of senior author Miguel Ramalho-Santos, PhD, who is an associate professor of obstetrics/gynecology and reproductive sciences at UCSF.
Bulut-Karslioglu and colleagues showed that paused embryos could quickly resume normal growth when mTOR inhibiters were removed, and developed into healthy mice if implanted back into a recipient mother.
Discovery was Surprise to Researchers
The discovery was a surprise to the researchers, who had intended to study how mTOR-inhibiting drugs slow cell growth in blastocysts, not to find a way to put the embryos into hibernation.
“It was completely surprising. We were standing around in the tissue culture room, scratching our heads, and saying wow, what do we make of this?” said Ramalho-Santos, who is a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research. “To put it in perspective, mouse pregnancies only last about 20 days, so the 30-day-old ‘paused’ embryos we were seeing would have been pups approaching weaning already if they’d been allowed to develop normally.”
Further experiments demonstrated that cultured mouse embryonic stem cells – which are derived from the blastocyst-stage embryo – can also be put into suspended animation by mTOR inhibitors. The drugs appear to act by reducing gene activity across much of the genome, the team found, with the exception of a handful of so-called “repressor” genes that themselves may act to inhibit gene activity. The researchers tested a number of different mTOR inhibitors and found that the most effective was a new synthetic drug called Rapa-Link that was recently developed at UCSF by the lab of Kevan Shokat, PhD.
The researchers believe that it should be possible to extend the suspended animation for much longer than the 30 days observed in the present study, Bulut-Karslioglu said: “Our dormant blastocysts are eventually dying when they run out of some essential metabolite within them. If we could supply those limiting nutrients in the culture medium, we should be able to sustain them even longer. We just don’t know exactly what they need yet.”
Drug-Induced Dormancy Mimics Natural Pausing
Bulut-Karslioglu and colleagues demonstrated that the dormant state they were able to induce in blastocysts by blocking mTOR was almost identical to the natural ability of mice to pause a pregnancy in its early stages. This temporary stasis, called diapause, occurs in species across the animal kingdom, and in mammals from mice to wallabies, it typically allows mothers to delay pregnancy when food is scarce or they are otherwise stressed.
It makes sense that mTOR would be involved in the process of diapause, Ramalho-Santos said: “mTOR is this beautiful regulator of developmental timing that works by being a nutrient sensor. It doesn’t just drive cells into growing willy-nilly; it tunes cell growth based on the level of nutrients that are available in the environment.”
It is an open question whether humans also have the ability to pause pregnancies at the blastocyst stage, Bulut-Karslioglu said, because the time from fertilization to implantation is hard to measure in humans. However, anecdotal accounts from practitioners of in vitro fertilization of unusually long pregnancies and mismatches between the timing of artificial embryo transfer and the resulting pregnancy suggest that humans too may have the ability to delay implantation of fertilized embryos in some circumstances.
Implications for Other Fields of Medicine
The new research could have a big impact on the field of assisted reproduction, where practitioners are currently limited by the rapid degradation of embryos once they reach the blastocyst stage. Putting blastocysts into suspended animation may avoid the compromise of freezing embryos and give practitioners more time to test fertilized blastocysts for genetic defects before implanting them, Bulut-Karslioglu said.
MTOR inhibitors are already in clinical trials to treat certain forms of cancer, but the new results suggest a potential danger of this approach, Ramalho-Santos said: “Our results suggest that mTOR inhibitors may well slow cancer growth and shrink tumors, but could leave behind these dormant cancer stem cells that could go back to spreading after therapy is interrupted. You might use a second or third line of drugs specifically to kill off those remaining dormant cells.”
The authors are eager to explore whether mTOR inhibitors and related downstream biochemical pathways can drive stem cells into a dormant state at later stages of development, which could have major implications efforts to repair or replace ailing organs in the field of regenerative medicine. The findings also have potential implications in aging research, the authors say, where mTOR inhibitors have already been shown to extend the lives of mice and other animals, an outcome which the authors suggest could result in part from preserving more youthful stem cells.
“This is a great example of the power of basic science,” Ramalho-Santos said. “We weren’t looking for ways to pause blastocyst development or mimic diapause. We weren’t trying to model aging or test cancer therapies or develop better techniques for tissue regeneration or organ transplantation. None of that was in our mind, but our experiments told us we were on to something we had to understand, and we couldn’t ignore where they led.”
A team of physicians and laboratory scientists has taken a key step toward a cure for sickle cell disease, using CRISPR-Cas9 gene editing to fix the mutated gene responsible for the disease in stem cells from the blood of affected patients.
For the first time, they have corrected the mutation in a proportion of stem cells that is high enough to produce a substantial benefit in sickle cell patients.
The researchers from UC Berkeley, UC San Francisco Benioff Children’s Hospital Oakland Research Institute (CHORI) and the University of Utah School of Medicine hope to re-infuse patients with the edited stem cells and alleviate symptoms of the disease, which primarily afflicts those of African descent and leads to anemia, painful blood blockages and early death.
“We’re very excited about the promise of this technology,” said Jacob Corn, a senior author on the study and scientific director of the Innovative Genomics Initiative at UC Berkeley. “There is still a lot of work to be done before this approach might be used in the clinic, but we’re hopeful that it will pave the way for new kinds of treatment for patients with sickle cell disease.”
In tests in mice, the genetically engineered stem cells stuck around for at least four months after transplantation, an important benchmark to ensure that any potential therapy would be lasting.
“This is an important advance because for the first time we show a level of correction in stem cells that should be sufficient for a clinical benefit in persons with sickle cell anemia,” said co-author Mark Walters, a pediatric hematologist and oncologist and director of UCSF Benioff Oakland’s Blood and Marrow Transplantation Program.
The results were reported in the Oct. 12 issue of the online journal Science Translational Medicine.
Sickle cell disease is a recessive genetic disorder caused by a single mutation in both copies of a gene coding for beta-globin, a protein that forms part of the oxygen-carrying molecule hemoglobin. This homozygous defect causes hemoglobin molecules to stick together, deforming red blood cells into a characteristic “sickle” shape. These misshapen cells get stuck in blood vessels, causing blockages, anemia, pain, organ failure and significantly shortened lifespan. Sickle cell disease is particularly prevalent in African Americans and the sub-Saharan African population, affecting hundreds of thousands of people worldwide.
The goal of the multi-institutional team is to develop genome engineering-based methods for correcting the disease-causing mutation in each patient’s own stem cells to ensure that new red blood cells are healthy.
The team used CRISPR-Cas9 to correct the disease-causing mutation in hematopoietic stem cells — precursor cells that mature into red blood cells — isolated from whole blood of sickle cell patients. The corrected cells produced healthy hemoglobin, which mutated cells do not make at all.
Future pre-clinical work will require additional optimization, large-scale mouse studies and rigorous safety analysis, the researchers emphasize. Corn and his lab have joined with Walters, an expert in developing curative treatments such as bone marrow transplant and gene therapy for sickle cell disease, to initiate an early-phase clinical trial to test this new treatment within the next five years.
Notably, research groups might be able to apply the approach described in this study to develop treatments for other blood diseases such as ?-thalassemia, severe combined immunodeficiency (SCID), chronic granulomatous disease, rare disorders like Wiskott-Aldrich syndrome and Fanconi anemia, and even HIV infection.
“Sickle cell disease is just one of many blood disorders caused by a single mutation in the genome,” Corn said. “It’s very possible that other researchers and clinicians could use this type of gene editing to explore ways to cure a large number of diseases.”
“There is a clear path for developing therapies for certain diseases,” said co-senior author Dana Carroll of the University of Utah, who co-developed one of the first genome editing techniques over a decade ago. “It’s very gratifying to see gene editing technology being brought to practical applications.”
The work is the fruit of the Innovative Genomics Initiative, a joint effort between UC Berkeley and UCSF that aims to correct DNA mutations that underlie human disease using CRISPR-Cas9, a pioneering technology co-developed by scientists at UC Berkeley that has made genome editing easier and more efficient than ever before.
The project also leverages the expertise of physicians and scientists at UCSF Benioff Children’s Hospital Oakland, a major center for research and treatment of sickle cell disease, and Carroll’s expertise in the field of genome engineering.
In addition to Corn, Walters and Carroll, other co-authors are Mark DeWitt, Nicolas Bray, Tianjiao Wang and Therese Mitros of UC Berkeley; Wendy Magis, Seok-Jin Heo, Denise Muñoz, Dario Boffelli and David Martin of CHORI; Jennifer Berman of Bio-Rad Laboratories in Pleasanton, California; and Fabrizia Urbinati and Donald Kohn of UCLA.
The research is supported by the National Institutes of Health, the Li Ka Shing Foundation, the Siebel Scholars Fund, the Jordan Family Fund and the Doris Duke Charitable Foundation.
Limb or organ regrowth may be hidden in our genes
If you trace our evolutionary tree way back to its roots — long before the shedding of gills or the development of opposable thumbs — you will likely find a common ancestor with the amazing ability to regenerate lost body parts. In an effort to understand what was lost, researchers have built a running list of the genes that enable regenerating animals to grow back a severed tail or repair damaged tissues.
A Duke study appearing April 6 in the journal Nature has discovered the presence of these regulatory sequences in zebrafish, a favored model of regeneration research. Called “tissue regeneration enhancer elements” or TREEs, these sequences can turn on genes in injury sites and even be engineered to change the ability of animals to regenerate.
The new cells prevented the onset of diabetes in an animal model of the disease bringing personalized cell therapy for diabetes closer.
Scientists at the Gladstone Institutes and the University of California, San Francisco (UCSF) have successfully converted human skin cells into fully-functional pancreatic cells. The new cells produced insulin in response to changes in glucose levels, and, when transplanted into mice, the cells protected the animals from developing diabetes in a mouse model of the disease.
The new study, published in Nature Communications, also presents significant advancements in cellular reprogramming technology, which will allow scientists to efficiently scale up pancreatic cell production and manufacture trillions of the target cells in a step-wise, controlled manner. This accomplishment opens the door for disease modeling and drug screening and brings personalized cell therapy a step closer for patients with diabetes.
For patients who’ve lost limbs, it’s a challenge is to put both their lives and their bodies back together.
Decades after he lost his leg in a hunting accident, Erik Ax walks with the confidence of a pioneer. “It’s just a new life when you get this system compared with the socket,” Ax said.
Ax became one of the first patients in the world to be fitted with an implanted post anchored directly to the bone in his leg.
Study Reveals Importance Of Timing For Cellular Signals, Suggests Possible Tactic For Cancer Therapeutics
Magic tricks work because they take advantage of the brain’s sensory assumptions, tricking audiences into seeing phantoms or overlooking sleights of hand. Now a team of UC San Francisco researchers has discovered that even brainless single-celled yeast have sensory biases that can be hacked by a carefully engineered illusion, a finding that could be used to develop new approaches to fighting diseases such as cancer.
“The ability to perceive and respond to the environment is a basic attribute of all living organisms, from the greatest to the smallest,” said Wendell Lim, PhD, the study’s senior author. “And so is the susceptibility to misperception. It doesn’t matter if the illusion is based on molecular sensors within a single cell or neurons in the brain.”
A Review article published on November 20 in Trends in Molecular Medicine highlights the promise and limitations of new methods based on stem cell and reprogramming technologies to generate biological pacemakers that might one day replace electronic pacemakers.
To create biological pacemakers, one approach is to coax stem cells to become specialized cardiac pacemaker cells that are normally found within the sinoatrial node of the heart.
Researchers need to better understand the mechanisms controlling the development and maintenance of pacemaker cells in the sinoatrial node, just as they must develop ways to compare experimental biological pacemaker tissue with bona fide sinoatrial node tissue.
“Biological pacemakers must meet a very high standard of performance to supplant electronic pacemakers,” Vedantham says.
Compound Restores Transparency to Mouse Lenses, Human Lens Tissue
Through these experiments, said Gestwicki, “We are starting to understand the mechanism in detail. We know where compound 29 binds, and we are beginning to know exactly what it’s doing.” The team next tested compound 29 in an eye-drop formulation in mice carrying mutations that make them predisposed to cataracts.
Similar results were seen when compound 29 eye drops were applied in mice that naturally developed age-related cataracts, and also when the compound was applied to human lens tissue affected by cataracts that had been removed during surgery.
He has licensed the compound from U-M and Makley, a former graduate student and postdoctoral fellow in the Gestwicki laboratory, is founder and chief scientific officer of ViewPoint Therapeutics, a company that is actively developing compound 29 for human use.
In addition to compound 29’s potential for cataract treatment, the insights gained through the research could have broader applications, said Gestwicki, a member of UCSF’s Institute for Neurodegenerative Diseases whose main research interest is dementia and related disorders.
Dramatic increases in exposure to toxic chemicals in the last four decades are threatening human reproduction and health, according to the International Federation of Gynecology and Obstetrics (FIGO), the first global reproductive health organization to take a stand on human exposure to toxic chemicals.
According to Di Renzo, reproductive health professionals “Witness first-hand the increasing numbers of health problems facing their patients, and preventing exposure to toxic chemicals can reduce this burden on women, children and families around the world.” Miscarriage and still birth, impaired fetal growth, congenital malformations, impaired or reduced neurodevelopment and cognitive function, and an increase in cancer, attention problems, ADHD behaviors and hyperactivity are among the list of poor health outcomes linked to chemicals such as pesticides, air pollutants, plastics, solvents and more, according to the FIGO opinion.
“What FIGO is saying is that physicians need to do more than simply advise patients about the health risks of chemical exposure,” said Jeanne A. Conry, MD, PhD, a co-author of the FIGO opinion and past president of the American College of Obstetricians and Gynecologists, which issued an opinion on chemicals and reproductive health in 2013.
“Given accumulating evidence of adverse health impacts related to toxic chemicals, including the potential for inter-generational harm, FIGO has wisely proposed a series of recommendations that health professionals can adopt to reduce the burden of unsafe chemicals on patients and communities,” said FIGO President Sabaratnam Arulkumaran, MBBS, who is also past president of the British Medical Association.
UC San Francisco researchers have for the first time developed a method to precisely control embryonic stem cell differentiation with beams of light, enabling them to be transformed into neurons in response to a precise external cue.
“We’ve discovered a basic mechanism the cell uses to decide whether to pay attention to a developmental cue or to ignore it,” said senior author Matthew Thomson, PhD, a researcher in the department of Cellular and Molecular Pharmacology and the Center for Systems and Synthetic Biology at UCSF.
Thomson’s ambitious big idea is to use the light-inducible differentiation technology his group has developed to study how stem cells produce complex tissues in three dimensions. He imagines a day when researchers can illuminate a bath of undifferentiated stem cells with a pattern of different colors of light and come back the next day to find a complex pattern of blood and nerve and liver tissue forming an organ that can be transplanted into a patient.