25 March 2014. Veterinary researchers at University of Maryland successfully bred 18 pigs with their genomes edited by a technique that prominent geneticists recently called for strict guidelines. The university today announced birth of the baby pigs bred by animal sciences professor Bhanu Telugu and faculty research assistant Ki-Eun Park.
Telugu and Park applied the technique known as CRISPR, short for clustered, regularly interspaced short palindromic repeats. CRISPR is adapted from a natural process used by bacteria to protect against attack by viruses, where a protein that deactivates or replaces genes binds to targeted RNA molecules generated by the human genome. The RNA molecules then guide the editing protein to specific genes needing repair.
The Maryland team is using a different approach to CRISPR. Instead of sending a protein to edit the genome, Telugu and Park are modifying nucleotides — biochemical building blocks in DNA and RNA — in the pigs’ genomes. The university says Telugu and Park and are pursuing a patent on this CRISPR technique.
Last week, in a statement published in Science, a group of leading genomics researchers, including some working directly in CRISPR, called for scientists, companies, and physicians to develop ethics guidelines for the use of CRISPR, particularly in research on human diseases. “Assuming the safety and efficacy of the technology can be ensured” said the statement, “a key point of discussion is whether the treatment or cure of severe diseases in humans would be a responsible use of genome engineering, and if so, under what circumstances.” A concern of the writers is that without a responsible road map for CRISPR, a public backlash against the technique could put a halt to the work done so far and prevent further applications in medicine.
Telugu and Park say their research is aimed for improving the welfare of animals, not humans. In September 2014, Telugu’s team received a $1.6 million grant from National Institute of Food and Agriculture, part of U.S. Department of Agriculture, to apply genome editing to improving the resistance of pigs to influenza. The Maryland researchers are studying ways of deactivating genetic receptors in pigs for the flu virus that in the past damaged herds, and led to swine flu pandemics among humans.
But research in pig genomes may still have implications for humans, since pigs have some organs and functions, such as in the digestive system that are similar to humans. Telugu and Park hope to extend their research beyond influenza to other conditions faced by humans, such as obesity and diabetes.
Human stem cell derived beta cells in mice (Doug Melton, Harvard University)
24 March 2015. A biotechnology start-up developing a stem-cell technology to replace missing beta cells that produce insulin for patients with type 1 diabetes, secured $44 million in its first venture funding round. Funding for Semma Therapeutics in Cambridge, Massachusetts was led by MPM Capital, with participation by Fidelity Biosciences, ARCH Venture Partners, and Medtronic.
Details about a separate agreement with the pharmaceutical company Novartis were not disclosed.
Semma Therapeutics is licensing research findings by its scientific founder biologistDouglas Melton, co-director of Harvard University’s Stem Cell Institute. Melton studies beta cells, which when functioning properly, produceinsulin in the pancreas. Insulin is a hormone that helps the body store and process glucose provided by food in the diet.
Type 1 diabetes is a condition where the body’s immune system is tricked into destroying beta cells. Some 3 million people in the U.S. havetype 1 diabetes, including many children and young adults, who need to replace their insulin supply daily through injections or devices such as insulin pumps.
Melton’s interest in type 1 diabetes goes beyond business and science. As reported in Science & Enterprise in October 2014, his son and daughter were diagnosed with type 1 diabetes as children, and he made finding a cure the goal of his career. Researchers in Melton’s lab designed a culturing protocol for transforming human embryonic stem cells into pancreatic and endocrine progenitor cells, and then into beta cells.
Their techniques enabled the team to generate hundreds of millions of beta cells in the lab that perform the same insulin-secreting functions, responding to glucose as normal mature beta cells. Tests of the beta cells in animals show their genes express similarly to normal beta cells, and enable control of blood glucose levels.
Semma Therapeutics is extending Melton’s discoveries into processes for implanting the engineered beta cells in people with type 1 diabetes so they function similar to people without the disorder, and that protects the recipients from an immune-system reaction.
The funds raised in this first venture round, plus the agreement with Novartis are expected to fund development of Semma Therapeutics’ technology through early clinical development that shows the solution is feasible. While the nature of the Novartis agreement was not disclosed, Novartis’s research labs are concentrating on autoimmune disorders as one of their key targets.
Ketamine vials (Licensed under Public Domain via Wikimedia Commons)
23 March 2015. A clinical trial is planned to test an anesthetic used in surgery as a treatment for Rett syndrome, a rare developmental disorder affecting girls. The trial testing the anesthetic ketamine will be conducted by Case Western Reserve University medical school in Cleveland, funded by a $1.3 million grant from Rett Syndrome Research Trust.
Rett syndrome is a genetic disorder affecting 1 in 10,000 to 15,000 female births, and while it is caused by a mutation in the MECP2 gene, the disease is not inherited. Symptoms of Rett syndrome are similar to autism, reflected in problems with communication, learning, and coordination, as well as breathing difficulties such as hyperventilation, beginning at about 6 months of age. Treatments for Rett syndrome generally involve management of symptoms and occupational skill therapy.
The clinical trial will test the ability of ketamine to reverse symptoms of Rett syndrome. Neuroscience professor David Katz at Case Western Reserve tested ketamine as a therapy for Rett syndrome in lab mice genetically engineered to exhibit the disease. Katz reports that low doses of ketamine were able to rebalance characteristic neurological activity of Rett syndrome in the mice and show improved neurological functions.
While ketamine is widely used a sedative and anesthetic in surgery, it also has a checkered history. Ketamine was a 1990s-era party drug known on the street as Special K, but is showing promise recently as a treatment for depression, working as quickly as 6 hours and with the capability of reducing suicidal thoughts. Due to ketamine’s potential for abuse and ability to cause adverse effects, such as nausea and hallucinations, clinicians are moving ahead cautiously with the drug.
“Because ketamine was initially developed for use in surgical anesthesia, it has never been used to treat a chronic illness,” says Katz in a university statement. “So one of the next questions will be whether we can develop a chronic dosing paradigm with this or similar drugs that would be safe and effective for patients with Rett syndrome.”
The trial led by Katz, and with colleagues at the Cleveland Clinic, plans answer those questions by enrolling 35 individuals with Rett syndrome. Participants will receive ketamine in various low doses or a placebo, in random order, in multiple 2-day sessions, with each session about a month apart. The researchers will look particularly at changes in breathing and behavioral symptoms.
23 March 2015. Two biotechnology companies are combining their expertise in neural stem cells and gene delivery to develop new cancer therapies that the parties say would be more effective with fewer side effects than chemotherapy drugs used today. While GenVec Inc. in Gaithersburg, Maryland will participate economically in the collaboration with TheraBiologics Inc. in Arcadia, California, financial and intellectual property details of their agreement were not disclosed.
The companies initially plan to enhance TheraBiologics’ TBX02, an experimental cancer treatment for delivery with GenVec’s gene therapy techniques. TheraBiologics commercializes research by co-founder Karen Aboody, a researcher at City of Hope medical center in Duarte, California that specializes in cancer care. Aboody studies neural stem cells as a vehicle for cancer therapies, with early findings showing the ability of neural stem cells to quickly find and penetrate tumors.
TBX02 is made of engineered neural stem cells, or NSCs, designed to emit carboxylesterase, an enzyme that converts the cancer chemotherapy irinotecan into SN-38, a compound believed to be 1,000 times more toxic to cancer cells than unmodified irinotecan. Development of TBX02 as a treatment for brain tumors is supported by an $18 million grant from California Institute of Regenerative Medicine, and currently in preclinical stages.
GenVec’s technology harnesses adenoviruses to deliver genetic therapies. Adenovirus vectorsare benign, naturally occurring microbes that can infect cells, but do not integrate with the cell’s genome or cause disease, and generate a mild immune response. This delivery technology is being tested to deliver healthy genetic material to treat inherited diseases, but also as a vehicle for cancer therapies.
The partnership aims to incorporate Genvec’s gene delivery technology to add more potency to TBX02, as well as provide TheraBiologics with a manufacturing process for the treatments. GenVec is expected to offer its experience in vector construction with technical and regulatory support, while TheraBiologics will be responsible for all other development costs.
“NSCs selectively target invasive cancer sites resulting in tumor-localized chemotherapy production, sparing the rest of the body from toxic side effects,” says Aboody in a joint statement. “GenVec’s technology provides us with a well-validated process for modifying these cells to reach their full therapeutic potential.”
20 March 2015. A statistical projection shows some 59,500 deaths over 15 years could be prevented if new cars in the U.S. had alcohol ignition locks that stop drunk drivers from starting their engines. Medical and transportation researchers at University of Michigan, led by professor of emergency medicine Patrick Carter, published their findings yesterday in American Journal of Public Health.
Carter and colleagues sought to measure the impact alcohol ignition locks would have on traffic fatalities and injuries, as well as the economic costs of accidents, if new cars in the U.S. were equipped with these devices. Alcohol ignition locks, also called ignition interlocks, read the driver’s blood alcohol concentration by measuring alcohol in the breath. If the driver’s blood alcohol concentration is above a specified point, usually somewhat below the legal blood-alcohol limit, the device locks the ignition, preventing the car from starting.
Most alcohol ignition locks today are installed in cars driven by people with convictions for impaired driving, including those with suspended or revoked licenses, to protect public safety and prevent repeat offenses. The Michigan team tested the impact of a policy that required alcohol ignition locks installed in all new cars, and breath tests to start a car any time. The authors say advances in alcohol ignition locks make newer devices less obtrusive and easier to use.
The Michigan team drew their data from the Fatality Analysis Reporting System and National Automotive Sampling System-General Estimates System data sets for 2006 to 2010. Fatality Analysis Reporting System is an annual census with data on all traffic accidents in the U.S. with 1 or more fatalities. National Automotive Sampling System-General Estimates System samples some 50,000 motor vehicle traffic accidents from police reports in 60 regions in the U.S., where at least 1 injury, death, or property damage occur.
The researchers constructed an algorithm to model the effect of a policy requiring alcohol ignition locks in all new cars. The model estimates the effects of alcohol ignition locks installed in all new vehicles less than a year old on traffic deaths and injuries, as well as the economic costs of alcohol-related accidents. The team then repeats that process for each subsequent year adding another model year’s worth of new cars to the total national fleet. The process is repeated for 15 years, a standard period for implementing new technologies in a vehicle fleet.
Carter and colleagues found that for the total 15-year period, a policy of mandatory ignition locks would prevent 83 percent of alcohol-related traffic fatalities, numbering more than 59,500. The policy would likewise prevent 84 to 88 percent or about 1.25 million non-fatal injuries. Cost savings related to alcohol-related injuries were calculated at $342 billion, with costs for the ignition lock devices recouped after 3 years.
According to the team’s estimates, younger drivers would benefit the most from a policy of mandatory alcohol ignition locks. Among drivers age 21 to 29, more than 481, 000 deaths and injuries would be prevented, representing more than one-third (35%) of total deaths and injuries. Among drivers under the age of 21 — below the legal drinking age in most states — nearly 195,000 deaths and injuries would be prevented.
Carter believes a mandatory alcohol ignition lock policy is particularly important for these younger drivers, given they tend to be the most persistent age group to drive when impaired. “By capitalizing on recent technological advancements that make alcohol-detecting sensors seamless to the driver,” says Carter in a university statement, “and applying such technology more broadly to all newly built vehicles, we can actually have a substantial injury prevention impact among traditionally hard-to-reach high-risk populations.”
Students and professors from the USAF Test Pilot School and University of Illinois. Naira Hovakimyan is second from the left. (Rebecca Amber, USAF)
20 March 2015. U.S. Air Force pilots tested a new flight control system designed by engineers at University of Illinois that automatically adapts aircraft to changing conditions faster than most human pilots can respond. The L1 adaptive control system is a product of the university’s Advanced Control Research Laboratory in Urbana, Illinois led by mechanical engineering professor Naira Hovakimyan.
A start-up company, Intelinair in San Jose, California, already licensed Hovakimyan’s technology from the university for control systems in unmanned aircraft used in research and agriculture.
Hovakimyan and colleagues are seeking a technology that provides an extra measure of safety for piloted aircraft, despite the excellent safety record of commercial aviation. “The flight control systems on today’s commercial aircraft have been tested and matured for decades and are considered very safe for the millions of passengers traveling on airplanes every day,” says Hovakimyan in a university statement. “But despite their safety, there is still great need for new technologies that could prevent more accidents.”
The L1 adaptive contol system aims to quickly respond to changing flight dynamics by separating adaption calculations from the robustness of the response needed to bring the aircraft under control. L1’s algorithms compute changes in the aircraft’s current status, but also calculate uncertainties in those conditions. Those calculations define the feedback loop that includes limitations placed on the robustness of a corrective response. This structure in the system, say its developers, makes it possible to detect changes in flight dynamics and quickly adapt to conditions safely, within the calculated boundaries.
In a project that ended in 2010, NASA asked a number of research groups to develop flight control systems, which the agency tested in small-scale aircraft. The lab says only 9 of the systems submitted to NASA qualified for flight testing, and L1 was the only system to provide consistent and reliable responses, including in stalls and post-stall conditions.
In early March, Hovakimyan’s lab flight-tested the L1 system for the first time at the Air Force’s Test Pilot School at Edwards Air Force Base in California, in a Calspan Learjet configured for evaluating new control systems. It was the first flight test for L1, and included pilots of F-16 fighters and B-52 bombers. The tests aimed to evaluate L1’s ability to control routine aircraft handling, and respond as well to abrupt hazardous in-flight conditions.
Among the hazardous failure conditions tested were changes in aerodynamics and a shift in the aircraft’s center of gravity, where pilots can sometimes overcompensate in their response, causing an even more dangerous situation. In all of the failure condition tests, say the researchers, the L1 system was able to safely respond to the problem and restore predictable and consistent performance. The test pilots later successfully performed eight touch-and-go landings of the L1 system, both in routine and failure conditions.
Hovakimyan would like to see L1 technology adopted by major airlines as a backup control system for their trained pilots. “If anything goes wrong, this would kick in,” she adds. “If there’s one switch that a pilot can turn on when the aircraft is in trouble, I want to see that happen.”
The following video from the Learjet cockpit shows test pilots engaging the L1 system under failure conditions.
19 March 2015. The pharmaceutical company Eli Lilly and Company is acquiring from Hanmi Pharmaceutical, an experimental drug that blocks the actions of an enzyme associated with rheumatoid arthritis and other autoimmune diseases. The deal can pay Hanmi, in Seoul, Korea, as much as $690 million.
Autoimmune disorders are diseases where the body’s immune system is tricked into attacking healthy cells rather than invading bacteria or viruses. Among the better known autoimmune diseases are rheumatoid arthritis, multiple sclerosis, and lupus. Women have a higher risk for autoimmune diseases, which are often characterized by inflammation, resulting in swelling and pain.
Hanmi is developing a small molecule — low molecular weight — drug code-named HM71224 to treat autoimmune disorders. HM71224 limits the actions of an enzyme known as Bruton’s tyrosine kinase, or BTK, essential for the development and maturation of B cells, a type of white blood cell that helps protect the body against infection.
BTK proteins send chemical signals instructing B cells to mature and produce antibodies. In some cases, however, BTK enzymes can trigger autoimmune reactions from B cells, where blocking their activity may relieve the resulting inflammation, swelling, and pain.
Hanmi designed HM71224 as an inhibitor of BTK enzymes. The company tested the drug in an early-stage safety clinical trial with 58 healthy volunteers in the Netherlands. In June 2014, the company reported results from the trial indicating HM71224 was successfully absorbed into the body with single and multiple doses, and was not affected by food intake.
Under the agreement, Hanmi is providing a license to Eli Lilly and Company to develop and commercialize HM71224 worldwide, except for China,Hong Kong,Taiwan, and Korea. In return, Hanmi is receiving an initial payment $50 million, and is eligible for another $640 million in development, regulatory, and sales milestones. If commercial products are developed from the partnership, Hanmi can also receive royalties on their sales.
The companies say HM71224 is ready for intermediate-stage clinical trials as a treatment for rheumatoid arthritis, lupus, and other autoimmune disorders.
19 March 2015. A graduate student in agriculture at University of California in Davis turned his research on irrigation technology into a new enterprise addressing the chronic drought conditions facing that state’s farmers. Tom Shapland started Tule Technologies Inc. in January 2014 that licensed his research measuring agricultural water use from the university.
Tule (pronounced tool-ee) provides growers with real-time measures of water use in their fields, a critical issue given California’s continuous drought conditions, now entering their fourth year. UC-Davis issued a report in July 2014 indicating that water availability is about one-third less than normal, the largest reduction the state has ever seen. The drought is estimated to cost California $22 billion in 2014, with a loss of more than 17,000 full- and part-time jobs. California’s Central Valley, one of the world’s leading agriculture regions, has been particularly hard hit.
Shapland, who received his doctorate in 2012 from UC-Davis’s College of Agricultural and Environmental Sciences, studied the turbulent exchange of energy and water vapor between crops and the atmosphere. With Davis faculty Andrew McElrone, Rick Snyder, and Kyaw Tha Paw U, Shapland designed a technology that monitors evapotranspiration in the fields, a combination of evaporation of water from the land surface and transpiration, or release of water from plant leaves. Their discoveries advanced the state of the art by making it possible to economically monitor much larger areas and provide instantaneous measurements of actual water use.
UC-Davis licensed the discoveries to Tule Technologies for commercialization. Tule, based in San Francisco, received seed funding and help with business formation at Y Combinator, a Silicon Valley incubator for high-tech start-ups. Twice a year, Y Combinator invests $120,000 in target companies and provides 3 months of training and mentoring to get the new enterprises off the ground. Tule was in one of Y Combinator’s 2014 classes.
For farmers in California today, closer monitoring of water is essential for a successful growing season. “Irrigation is the most important decision a farmer makes,” says Shapland in a university statement. “Irrigation, more than any other factor, is going to influence how much yield — how much produce — they get from their field and the quality of that produce.”
Tule leases sensors for $1, 500 each for a growing season, that can each monitor evapotranspiration in an area as large as 10 acres. The real-time water measurements provided by sensors enable growers to accurately gauge the amount of irrigation needed to replace the water lost. In addition, Tule’s system offers immediate water replacement calculations and forecasts for the upcoming week.
The company says it now has some 60 customers leasing 250 sensors, with 90 percent of the installations in California’s wine country. With new groundwater legislation in California putting more water-management demands on growers, however, Shapland expects the customer base to grow into other crops, and the company to grow with it. Tule’s current staff of 5 is now hiring software engineers at 6-figure salaries.
Presidential signature on the Affordable Care Act (whitehouse.gov)
18 March 2015. As the U.S. approaches the fifth anniversary of the Affordable Care Act, a new report from consulting firm PricewaterhouseCoopers highlights five major trends transforming the country’s health care sector, including creation of 90 new companies. The report, “Healthcare reform: Five trends to watch as the Affordable Care Act turns five,” is available for downloading from PwC’s Health Research Institute Web site.
The report compiles data from studies conducted by PwC’s Health Research Institute and other public sources, and argues that the country is developing a new health care economy, fundamentally changing business models in the industry valued at $2.9 trillion and accounting for 18 percent of GDP. No piece of legislation since the Telecommunications Act of 1996, says the report, sparked this degree of change in a major economic sector. Even with a Supreme Court challenge to one of the law’s basic features and reemergence of rising costs as a concern, the trends unleashed or encouraged by the Affordable Care Act are here to stay.
One of the five key trends is the entry of many new companies into the health care industry offering technology-based services, directly as a result of provisions in the Affordable Care Act or taking advantage of changes in health care delivery generated by the law. PwC identifies 90 of these enterprises, with nearly 1 in 3 (29 of 90) of the companies providing telehealth services, remotely connecting patients to clinicians. An example is CellScope Inc. in San Francisco, a spin-off company from University of California in Berkeley, developing an iPhone-based diagnostic toolkit.
Another 15 companies offer health consumer education services, such as Zest Health in Chicago developing a smartphone app to navigate through their health benefits, schedule appointments, compare costs for services, and get advice from a “nurse concierge.” Nearly the same number of new enterprises, 14, provide process-improvement services to improve efficiencies among health care professionals or enhance the patient experience. An example is Cureatr Inc. in New York that provides secure messaging and clinical workflow tools for health care providers on a mobile-device platform.
Some 9 new companies match patients and physicians with treatment and support networks, such as Smart Patients Inc. an online community connecting patients with clinical trials. Another 9 companies provide health and wellness benefit services for individuals or insurance companies, including EveryMove Inc., an online community encouraging fitness tracking on mobile devices.
PwC’s report identifies 7 companies offering analytics services, including Flatiron Health Inc. in New York that provides data analytics for cancer research and therapeutics. (Science & Enterprise profiled Flatiron Health’s collaboration with a genomics analysis enterprise in December 2014.) Another 7 companies develop new delivery and payment models, such as Aledade Inc. in Bethesda, Maryland, that helps primary care physicians form accountable care organizations, groups of health care providers, who come together voluntarily to give coordinated high quality care to their patients.
New payment and delivery models figure prominently in the four other major trends generated by the Affordable Care Act:
– The emergence of primary care as a key element in health care delivery, with experiments in new payment models and expansion of insurance coverage centered around primary care.
– Development of new payment models and schemes that spread more risk from insurance companies to health care providers, pharmaceutical companies, and consumers. These models include rewards for improved health outcomes and penalties for high rates of readmission and hospital-acquired conditions, as well as pay-for-performance, shared savings, and bundled payments.
– Shift in health insurance marketing from wholesale — e.g., employer-provided — markets to retail marketplaces, such as health insurance exchanges, forcing large-scale changes the way health insurance providers do business. The report highlights private health insurance exchanges that supplement the public exchanges.
– Emergence or reemergence of individual states as key players in health insurance and finance, including design of health insurance exchanges and expansion of Medicaid.
While the Supreme Court may still invalidate insurance exchanges offered by the Federal government and a Republican Congress will continue trying to repeal or defund the law, the report says the forces unleashed by the Affordable Care Act will not likely be stopped. Staying relevant in the U.S. health care sector, says PwC, requires “the willingness toinnovate: to develop strategies that meet the demands of new health care consumers, to pursue alternative business models, to adopt new technologies and to take on new roles and activities.”
Sensor-bandage to detect tissue damage leading to bedsores (Univ of California, Berkeley)
18 March 2015. A device with tiny electronic sensors in a flexible bandage is able to detect the earliest stages of tissue damage leading to pressure ulcers or bedsores, in tests with lab animals. The findings of research engineers from University of California in Berkeley and clinicians from University of California in San Francisco appear in yesterday’s issue of the journal Nature Communications (paid subscription required).
The team led by Berkeley engineering professor Michel Maharbiz sought a way of detecting changes in skin and underlying tissue before they become visible damage and then open sores. Bedsores result from prolonged pressure on skin, particularly in bony areas such as hips, tailbone, and heels. People confined to beds or wheelchairs due to medical condition, especially in hospitals or nursing homes, are most at risk.
Maharbiz and colleagues adopted a technique called impedance spectroscopy that gauges organic changes in skin cell health by measuring changes in electrical current. Healthy cell walls act like an insulator, and as skin cell walls start to break down from the continuous pressure, more electric current leaks through, and detected by the device.
The bandage has dozens of electrodes implanted in a flexible strip worn on the skin over areas most likely to form bedsores. With the sensor-bandage, impedance spectroscopy maps changes in tissue structure reported by the electrodes that could lead to bedsores by identifying where variations in electrical current are occurring.
The Berkeley-San Francisco team simulated bedsores in lab rats, by squeezing their bare skin between magnets for 1 to 3 hours. After removing the magnets, inflammation and oxidative stress occurred in the skin, with mild and reversible damage evident after 1 hour and greater — even permanent — damage occurring after the magnets remained in place for 3 hours. The researchers applied sensor-bandages to the damaged skin once a day for 3 days, and found the impedance measurements correlated strongly with the health of the tissue.
Maharbiz believes the smart-bandage technology can be applied to more disorders than bedsores. “As technology gets more and more miniaturized” says Maharbiz in a UC-Berkeley statement, “and as we learn more and more about the responses the body has to disease and injury, we’re able to build bandages that are very intelligent.” Co-author David Young, professor of surgery at UC-San Francisco, is leading a clinical trial of the technology.
Mharbiz tells more about the sensor-bandage in the following video.
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