Heart-on-a-chip device (Anurag Mathur, Healy Lab, Univ. of California-Berkeley)
9 March 2015. A bioengineering team at University of California in Berkeley developed a device with cardiac tissue derived from stem cells that can test drug candidates for potentially toxic effects. Researchers from the lab of engineering professor Kevin Healy published their findings today in the journal Scientific Reports.
Healy and colleagues created this device as part of the Tissue Chip for Drug Screening project, an initiative of National Institutes of Health, Food and Drug Administration, and Defense Advanced Research Projects Agency or Darpa. That initiative aims to come up with alternatives to preclinical toxicity tests using animals, because of their high error rates, before drug candidates reach the stage of human clinical trials.
With the high costs and long durations needed to develop drugs, say the authors, fast and inexpensive methods are needed to find candidates that will work and those that won’t. Screening is particularly needed for drugs that may cause adverse effects in the heart, which account for one-third of drug withdrawals based on safety factors.
The researchers designed the device with a three-dimensional structure comparable to connective tissue in the heart. Heart cells arrayed on the device were derived from human-induced pluripotent stem cells, adult stem cells that can transform into various types of tissue cells. The heart cells then were fed through a funnel-shaped receptacle and distributed on a silicone chip about 1 inch long. The chip also has tiny channels that emulate blood vessels, and their functions in the diffusion of drugs and nutrients in human tissue.
In about 24 hours after seeding the chip, heart tissue cells on the device began beating at 55 to 80 beats per minute, a rate similar to a human heart. The authors report being able to keep the heart tissue cells beating 2 to 3 weeks after seeding the chip.
To test the concept, the researchers exposed the generated heart tissue to 4 heart drugs in concentrations comparable to recommended human dosages:
– E-4031, a potassium channel blocker for treating heart rhythm problems
– Verapamil, a calcium channel blocker to treat high blood pressure and control chest pain
– Metoprolol, also a treatment for high blood pressure and chest pain, as well as to improve survival after a heart attack
The team reports the four drugs affect heart beat rates on the device as expected, if given to patients. Isoproterenol, for example, causes increases in heart rate that vary depending on the dosage, while verapamil has the opposite effects, causing decreases in beat rate, also depending on the dosage.
The researchers envision adapting the chip to test for human genetic diseases or screen drugs for an individual’s reactions to drugs, not just for populations overall. Chips for screening toxicity in the heart could also be combined on a single wafer with chips emulating other organs, like the liver, to test for a broader range toxic effects. “Ultimately,” says Healy in a university statement, “these chips could replace the use of animals to screen drugs for safety and efficacy.”
The following brief (22-second) video demonstrates the device with beating heart tissue, as well as the effects of drug exposure.
Vision testing of astronauts in microgravity (NASA.gov)
9 March 2015. Three companies are each receiving $100,000 in early-stage funds from a challenge seeking technologies to diagnose or correct eye problems in space faced by astronauts. The awards are made by National Space and Biomedical Research Institute (NSBRI) at Baylor College of Medicine in Houston, from its Vision for Mars Challenge.
The Vision for Mars competition, announced in November, sought solutions for vision problems astronauts encounter in long-duration space flights. In post-flight surveys, National Aeronautics and Space Administration found 29 percent of shuttle and and 60 percent of space station astronauts reported declines in distant and near-vision visual clarity. Anecdotal reports from returning astronauts also tell of difficulties in focusing cameras and other tasks requiring close visual inspection.
Among the winning competitors is Annidis Inc. in Grandville, Michigan, that develops devices to diagnose and treat eye disorders such as age-related macular degeneration, diabetic retinopathy, and glaucoma. NSBRI highlighted the company’s multi-spectral imaging technology for early detection of disorders of the retina and choriod, the layer connecting the retina and the clera, or white part of the eye. Annidis says its device provides diagnostic images rivaling more complex and invasive methods, and can complement NASA’s current diagnostic tools.
Another challenge winner is Equinox LLC in Sioux Falls, South Dakota. Equinox develops a device known as balance goggles that the company says can help regulate pressure inside the eye. “We believe that astronauts may be experiencing reverse glaucoma, which means they experience moderate pressure in the brain that pushes outward and onto the eye, causing some of the ocular pathologies,” says Dorit Donoviel, NSBRI’s deputy chief scientist in an institute statement. Balance goggles are expected to apply gentle pressure on the exterior of the eye to stabilize the internal pressure from inside the eye, and can be worn for extended periods making them suitable for long space flights.
The third funding recipient is Web Vision Centers Group in South Jordan, Utah, a business development company specializing mobile app and eye care technologies. Web Vision Centers Group is expected to offer prescription-adjustable glasses that can change their properties through techniques such as a computer plug-in, or magnetized lenses with different properties that can be inserted or removed by the wearers as needed.
The awards were made through the Space Medical and Related Technologies Commercialization Program, or Smartcap, administered by the institute’s industry members. Smartcap offers R&D funding for small companies in the U.S. to develop technologies related to NSBRI’s mission, as well as collaborate with NSBRI and its research partners. Smartcap awards are made three times a year and require matching funds from the recipients. The next deadline for applications is 26 June.
Mouse bone cells cultured on nanofibers (National Science Foundation)
6 March 2015. A new challenge on InnoCentive is seeking novel ways of using unique properties of nanofibers to treat human diseases. The competition as a total purse of $10,000 and a deadline of 3 April 2015.
InnoCentive in Waltham, Massachusetts conducts open-innovation, crowdsourcing competitions for corporate and organization sponsors. The sponsor, in this case, is not disclosed. Innocentive calls this type of competition an ideation challenge that requires a brief written proposal.Free registrationis required to see details of the competition.
The sponsor is seeking new methods that take advantage of properties of nanofibers, synthesized from polymers and typically 50 to 1,000 nanometers in diameter, with 1 nanometer equal to 1 billionth of a meter. Those properties — including size, porosity, and elasticity — make it possible to simulate fibrous qualities of the matrix supporting cells.
Among the potential applications is tissue engineering, where nanofibers can be arrayed into scaffolds similar to collagen supporting the growth of replacement cells and generation of new tissue. Another application is drug delivery, taking advantage of some nanofibers that have a high affinity for human tissue. Depending on the material, nanofibers could be adapted for delivering drugs to skin or oral surfaces, as well as into cancerous tumors or to organs such as heart or lungs.
InnoCentive says the sponsor of the competition is particularly interested in completely new applications that have not yet been explored. Competitors should identify unmet needs in diseases or conditions and describe ways nanofibers could address the problem that are different from what’s being done now.
This ideation challenge requires a brief (two-page) proposal. Ideation proposals can contain ideas originating from the participants, ideas from the public domain where no restrictions are applied, or ideas from third-parties where participants have the rights propose solutions with those ideas. Participants are asked not to submit confidential information in their proposals.
The competition has a total prize fund of $10,000, with at least one award no smaller than $4,000 and no award smaller than $2,000. The sponsor guarantees at least one prize will be awarded. The sponsor also indicates that submitting a proposal grants the sponsor a non-exclusive, perpetual, and royalty-free license to use any information in the proposal, including for promotional purposes. An exclusive transfer of intellectual property rights to the sponsor, however, is not required.
Nurse giving vaccine to an infant in Nicaragua (Bill & Melinda Gates Foundation)
6 March 2015. The Bill and Melinda Gates Foundation is making an equity investment and providing a grant to support research at CureVac GmbH, a developer of vaccines and therapies with RNA molecules. The foundation is investing €46 million ($52 million) in CureVac, in Tübingen, Germany, but the amount of the grant supporting research in vaccines at CureVac was not disclosed.
CureVac’s technology adapts messenger RNA, nucleic acids related to DNA that leave the cell nucleus and go to cells’ protein-making components. Those cell components synthesize human proteins by reading and translating the genetic code in messenger RNA into the appropriate amino acids for that protein.
The company’s technology is based on research by Ingmar Hoerr in the 1990s — Hoerr is one of CureVac’s founders — who discovered a way of controlling RNA that was previously considered too unstable for use as a treatment or vaccine. Since its founding in 2000, CureVac built three business lines based on that underlying technology.
– RNActive engages messenger RNA, or mRNA, to simulate the immune system for vaccines to protect against infectious diseases and supply immunotherapies for cancer.
– RNAdjuvant harnesses supporting RNA molecules to amplify immune response quality and quantity, and provide a boost to vaccines or immunotherapies
– RNArt adapts messenger RNA to trigger production of proteins in the body for direct disease treatments.
The Gates Foundation investment and research support aim to accelerate CureVac’s work on vaccines to prevent infectious diseases. Vaccines based on messenger RNA developed by CureVac, including two products now in early-stage clinical trials, are able to be stored and shipped without refrigeration, which makes them desirable for low-resource regions, a key requirement for backing by the Gates Foundation.
Proceeds from the Gates equity investment are expected to help CureVac continue developing its technology platforms, and build an industrial-scale manufacturing facility meeting Good Manufacturing Practice standards. CureVac’s first investor, the German life sciences venture capital company dievini Hopp BioTech, also plans to add another €21 million ($24 million) in capital to the company.
In addition, the Gates Foundation is providing a separate grant to CureVac as part of a collaboration on vaccines against infectious diseases that disproportionately affect people in the world’s poorest countries, including viral, bacterial, and parasitic disorders. CureVac and the foundation are already collaborating on vaccines for rotavirus and HIV.
“If we can teach the body to create its own natural defenses, we can revolutionize the way we treat and prevent diseases,” says Bill Gates in a joint statement. “Technologies like mRNA give us confidence to place big bets for the future.”
5 March 2015. A clinical trial testing a stem cell therapy for spinal cord injury is recruiting patients at an Atlanta rehabilitation center. The intermediate-stage trial, conducted by biotechnology company Asterias Biotherapeutics, aims to initially enroll 13 adults to test three dosage levels of neural stem cells designed to restore motor functions to spinal cord injury victims.
Spinal cord injuries are usually caused by a sudden, traumatic blow to the spine that bruises or tears into spinal cord tissue, resulting in fractures or compression to vertebrae, or in some cases severing of the spinal cord. Depending on severity, people with spinal cord injuries often suffer loss of feeling or motor function in the limbs, and in some cases complete paralysis. According to the National Spinal Cord Injury Statistical Center, spinal cord injuries occur in 40 out of 1 million people in the U.S., adding some 12,500 new cases each year.
Asterias, in Menlo Park, California, acquired stem cell therapies in development by Geron Corporation, including a treatment for spinal cord injury that Asterias code-names OPC1. The treatments are derived from human embryonic stem cells, which are cultured into oligodendrocyte progenitor cells, then transplanted to regenerate into functioning spinal cord nerve cells. Studies with lab animals show transplanted human oligodendrocyte progenitor cells are capable of restoring some limb functions.
In an early-stage safety test of OPC1, Asterias says 5 patients with spinal cord injuries at the Shepherd Center, a rehabilitation hospital in Atlanta for people with spinal cord injuries, showed the patients suffered no adverse effects from the treatments, the trial’s main objective. In 4 of the 5 patients, who suffered their injuries 7 to 14 days prior to the treatments, MRI scans revealed reduced hollowing out of spinal cord tissue may have occurred, suggesting at least some therapeutic benefit from the treatments.
The next clinical trial will also test for safety of the treatments, but will give the 14 patients with recent injuries — 14 to 30 days following the event — single injections of 2 million or 10 million OPC1 cells, or 2 injections of 10 million cells. The study also plans to evaluate the patients’ neurological functions based on a standard scale of motor capabilities at various intervals, up to 1 year following the injections. The new trial, also at the Shepherd Center, is funded by a $14.3 million grant from the California Institute for Regenerative Medicine.
Asterias says it plans to accelerate the schedule for the new trial and ask the U.S. Food and Drug Administration for permission to expand the study to 40 patients. In November 2011, Geron halted its work on stem cell treatments for spinal cord injuries to focus on cancer therapies, which the company’s CEO attributed to “the current environment of capital scarcity and uncertain economic conditions.”
5 March 2015. A University of Washington research team developed a synthetic polymer that in lab animals acts like natural proteins to form blood clots to stop heavy bleeding, a common danger in trauma cases. The group led by Washington bioengineering faculty Suzi Pun and emergency medicine professor Nathan White published its findings yesterday in the journal Science Translational Medicine (paid subscription required).
University of Washington applied for a patent on the blood-flow controlling materials described in the research, with Pun, White, and first author Leslie Chan listed as the inventors.
The researchers were seeking a more effective way of controlling heavy bleeding often associated with traumatic injury. National Trauma Institute estimates bleeding accounts for 35 percent deaths before trauma victims reach a hospital, and 40 percent of deaths overall in the first 24 hours after the injury. The loss of blood leads to immediate complications, such as shock, and further issues including organ failure and infections. Current methods to control excessive bleeding that require infusions of purified blood and clotting factors are expensive and have a limited shelf life.
Heavy bleeding associated with trauma can exceed the body’s ability to form clots for stopping the blood flow and encourage healing. Normal blood coagulation traps platelets and other blood cells in protein fibers known as fibrin. That process is aided by an enzyme called factor XIII that strengthens and stabilizes the formation of wound-healing blood clots.
Pun, White, and colleagues designed a synthetic polymer that acts like factor XIII in the blood, and could be injected into trauma victims. The synthetic polymer that the researchers call PolySTAT combines two biocompatible and water-soluble polymers that encourage the fibrin and platelet cells to coagulate. PolySTAT also includes a peptide that makes the polymer coagulate only with fibrin, and thus discourage formation of blood clots causing strokes or embolisms.
Tests in lab simulations of fluid flow show fibrin exposed to PolySTAT form tighter coagulations than fibrin relying only on factor XIII. Further tests show fibrin enhanced with PolySTAT strengthens clots, while retaining their elasticity and resisting degradation from plasmin, an enzyme that weakens proteins in blood, including fibrin. The authors say the materials in PolySTAT are all available commercially.
The team then tested PolySTAT in lab rats with artery wounds causing severe bleeding. Rats treated with PolySTAT injections had much lower bleeding rates — as much as 11 times less — than untreated rats or those given additional factor XIII. Rats give PolySTAT also needed less fluid replacement and had longer survival times than untreated rats or those given other substances. The researchers found PolySTAT was cleared by the rats’ kidneys and livers, with no differences in functioning of these organs compared to rats who were not given PolySTAT.
The authors note that the process used to prepare PolySTAT, known as reversible addition fragmentation chain transfer or RAFT polymerization is already used in industry and offers an economic method for producing PolySTAT with production, storage, and safety advantages compared to biologic products. PolySTAT, say the authors, could also be applied to treat disorders such as factor XIII deficiency or other forms of hemophilia.
Milo, humanoid robot for teaching children with autism (A. Kotok)
4 March 2015. Milo, a humanoid robot designed to engage and build social skills in children with autism spectrum disorder, was shown today at a press conference in Washington, D.C. The demonstration also reported on early research findings that suggest Milo can reach some children with autism to develop their social interactions.
Autism spectrum disorderis a collection of neurodevelopmental conditions, marked by communication difficulties and impaired social interaction, as well as repetitive and stereotyped patterns of behavior. Some 1 in 68 children have autism spectrum disorder, according to Centers for Disease Control and Prevention, with males 5 times more likely to have the disorder than females. Classic autism is considered the most severe form of the syndrome.
Milo is made by RoboKind, a developer of robotics for social engagement. Pamela Rollins, a professor of communications disorders at University of Texas in Dallas presented early results of tests with Milo and Robots4Autism curriculum for building social skills among children with autism spectrum disorder.
At the demonstration, held at National Press Club, Rollins outlined the curriculum, which she says reflects her research evidence and others. The curriculum has modules covering conversations, social situations, and emotional understanding, providing practical advice to children in simple interactions, like greetings, and more complex situations, such as birthday parties. Emotional understanding modules cover interpretation of facial expressions and understanding emotions of others.
Milo is a two-foot tall humanoid robot with child-like facial features and voice, and whose arms move and facial expression can change as needed. The robot also has sensors to gauge eye contact — often a problem for children with autism spectrum disorder — as well as cameras and microphones to record interactions.
Pamela Rollins (A. Kotok)
The embedded software includes the Robots4Autism curriculum and components for reporting the child’s interaction and progress. Children and their therapists use tablets to interact with Milo, in addition to input to Milo’s sensors.
Rollins says her research aims to build on earlier work assessing the feasibility of robots for helping children with autism, and develop a better understanding of the differences among children with the disorder in their levels of engagement with robots like Milo. She presented initial results of her study with 9 children, ages 5 to 14, all of whom had the skills needed to operate the tablets. Data collection, says Rollins, is still underway.
The findings show mixed results for children with autism in dealing with Milo. Children in the study were divided into two groups based on their previous level of social responsiveness, and measured on their level of engagement with Milo or their student therapists.
The results, supported by video of individual cases, show children with higher social functioning levels engage more with Milo when the robot initiates the interaction (88%), than when the children take the lead (81%). Children with lower levels of social functioning are only slightly more likely to engage with Milo when the robot initiates the interaction (68%) than when the children take the initiative (65%).
Observations of interactions with the robots show higher-functioning children are more likely to interact with Milo as a friend, while the lower-functioning children took a longer period to warm up to the robot. Engagement with therapists alone, without the presence of Milo, is much lower among all children in the study — between 2 and 4 percent — across both social skill levels.
Brad Baird, chief operating officer of RoboKind says the implications of tools like Milo for educators are significant. He cited data from Centers for Disease Control and Prevention that it costs $17,000 a year to teach each child with autism spectrum disorder. Early intervention strategies in children with the disorder, Baird says, can save the state of Texas alone some $2.9 billion.
Editor’s note: Text updated, 6 and 9 March 2015, to give more recent data on the rate of occurrence for autism spectrum disorder and more complete results of the research presented at the briefing.
3 March 2015. A collaboration between a social enterprise and lighting technology company aims to develop a laser device to control disease-carrying mosquitoes without pesticides. Financial details of the partnership between Global Good and Lighting Science Group, a designer of advanced industrial and residential lighting systems, were not disclosed.
Global Good brings together government, business, and not-for-profit organizations to develop new technologies to improve the life of residents in the poorest regions in the world. The organization is a partnership between Microsoft founder Bill Gates and new technology developer Intellectual Ventures in Bellevue, Washington. Intellectual Ventures acquires patent rights to new inventions, then arranges their licensing, financing, and development with business and not-for-profit organizations as sponsors.
One of the inventions acquired by Intellectual Ventures is a laser-based alternative to pesticides for controlling mosquitoes, including those that spread diseases, such as malaria. According to World Health Organization, malaria occurs in nearly 100 countries, with some 207 million cases in 2012, causing 627,000 deaths. The disease is spread through infections from a parasite spread by female Anopheles mosquito bites, where the parasite multiplies in the liver, then infects red blood cells. Symptoms, including headache, fever, and vomiting, occur 10 to 15 days following transmission from a mosquito.
The laser device, called a photonic fence, contains cameras to spot flying insects, LEDs to illuminate the target, sensors to measure the wing speed and other unique characteristics of the female mosquito, and controllers to aim an ultraviolet laser beam to hit the mosquito. On-board software distinguishes the female mosquito from males (that don’t spread disease) and other insect species, determines no bystanders are in the line of sight, and then shoots a beam strong enough to kill the mosquito.
The photonic fence is designed to protect the perimeter of a designated area, such as a clinic, and would complement other control measures, such as bed nets. A deployed system would also use a minimum of power to kill mosquitoes, so the photonic fence can run on a self-contained power source, such as solar panels. Its developers believe the technology can also be applied to protecting crops from flying insects, also without chemical pesticides.
Lighting Science, in Melbourne Florida, develops LED industrial and residential lighting solutions that the company says are more environmentally friendly and energy efficient than traditional light sources. Under the deal with Global Good, Lighting Science is licensing the photonic fence technology from Intellectual Ventures to develop prototypes for field testing in health, commercial, and residential applications.
The parties believe the collaboration can have benefits beyond malaria control. “What began by putting the world’s deadliest animal, the mosquito, in our sights with a laser, has opened up new advances in the way we can use light to protect communities and crops from a range of disease-bearing insects,” says Global Good vice president Maurizio Vecchione in a joint statement. “For example, the export potential of high-value crops could increase dramatically if a light-based perimeter was available to both monitor and eliminate pests, instead of possibly unsafe or ineffective insecticides.”
The following 1-minute video shows mosquitoes on the receiving end of a photonic fence laser beam.
Biosensors drawn directly on the skin (Jacobs School of Engineering/UC San Diego)
3 March 2015. Researchers at University of California in San Diego developed a way to create bioactive inks to use in hand-drawn sensors when needed at the point of care and other applications in the field. The team from the lab of nanoengineering professor Joseph Wang reported on their proof-of-concept findings last week in the journal Advanced Healthcare Materials (paid subscription required).
The San Diego team was seeking simple techniques to create sensors for tests involving biological processes, such as detection of pathogens or biological agents, health screening, and environmental monitoring. The solution needed to be safe for animals (including humans) and plants, adhere to surfaces, conduct an electric current, and easy to store and apply when needed.
Wang and colleagues tested a number of compounds and materials with the capability to meet these conditions. One of the key ingredients in their solution is polyethylene glycol, a biocompatible polymer found in cosmetics and skin creams as a binder and emulsifier, as well as over-the-counter medications, such as laxatives. For electrical conductivity, the researchers added graphite powder.
For the ink to stick to surfaces after being applied, researchers added chitosan, a natural sugar found in the hard outer skeleton of shellfish and used in wound dressings to stop bleeding. They also included xylitol, a naturally occurring alcohol used as a sugar substitute, but in this case to stabilize the active enzymes for testing added to the inks.
The team then loaded the inks into standard off-the-shelf ballpoint pens to be dispensed and applied. The first demonstration was to test for blood sugar or glucose levels, with a test enzyme added to the ink. Participants in the test drew a specified test pattern on a flexible plastic strip fitted with an electrode. The subjects next drew a drop of blood from a fingertip and spread the blood on the strip, which recorded their glucose levels, and transmitted the readings to a measuring device. The subjects then cleaned the strip and repeated the test after a meal, showing changes in glucose levels.
In a similar test, the researchers showed test patterns could be drawn directly on the skin rather than using a plastic strip. The readers were then transmitted over a Bluetooth link to a potentiostat, a device for measuring biochemical reactions.
A different test showed the inks could be applied to test for the presence of pollutants or hazardous materials. The researchers added enzymes to test for the compound phenol, also known as carbolic acid, an industrial chemical found in cosmetics and sunscreen, but also considered toxic by regulatory authorities in the U.S. and overseas. The team drew test patterns with the phenol test ink on leaves, then dipped the leaves in a water mixed with phenol, with readings on a connected pollution detector showing the presence of phenol in the water.
Wang and colleagues next plan to develop more wireless links to the hand-drawn sensors, and test the process further in more demanding conditions, such as extreme temperatures and longer exposure to sunlight.
Adam Gazzaley (University of California, San Francisco)
2 March 2015. A clinical trial plans to begin recruiting participants to test a video game designed to engage areas of the brain for building cognitive skills affected by autism. The trial, conducted by Akili Interactive Labs that developed the game, is funded by Delivering Scientific Innovation for Autism or Delsia LLC, a subsidiary of the foundation Autism Speaks for supporting technologies to treat the disorder. Financial details were not disclosed.
Autism spectrum disorderis a collection of neurodevelopmental conditions, marked by communication difficulties and impaired social interaction, as well as repetitive and stereotyped patterns of behavior. At age 8, some 1 in 88 children have autism spectrum disorder, according to Centers for Disease Control and Prevention. Classic autism is considered the most severe form of the syndrome.
Akili Interactive Labs is a spin-off enterprise from University of California in San Francisco, based on research from the lab of neuroscientist Adam Gazzaley, a co-founder and scientific advisor to the company. Gazzaley and colleagues at UCSF designed a video game to detect signs of cognitive decline among elderly individuals, and discovered that the game not only detected cognitive decline, it also had therapeutic effects. The researchers found participants who played the game over 4 weeks improved the subjects’ memory and cognitive skills.
Gazzaley went on the start Akili in 2011, under the tutelage of life sciences start-up accelerator PureTech Ventures in Boston. The company is applying Gazzaley’s concepts to detection and treatment of cognitive deficits, but to a broader population, including children.
Akili’s first program is a platform called EVO that uses a tablet- or smartphone-based electronic game to test multi-tasking skills. EVO requires players to guide a friendly alien down a river, while tapping the screen when a designated animal appears. The company says the game gets progressively more difficult, automatically adapting to the player’s ability level, and capturing progress by the participant.
The clinical trial aims to recruit 125 individuals, age 8 to 16, diagnosed with autism spectrum disorder and attention deficits. Sites for the trial are expected to be selected later this year. Autism Speaks says the EVO project, supported by Delsia, could serve as a model for other technology-based therapies for autism.
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