Conor Evans (Massachusetts General Hospital)
1 October 2014. Researchers at Massachusetts General Hospital in Boston developed a paint-on covering for severe wounds that changes color to indicate the extent of healing taking place. The team from the lab of Conor Evans in Mass. General’s photomedicine center published its findings in today’s issue of Biomedical Optics Express, published by the Optical Society.
The Evans team — including colleagues from Harvard Medical School, affiliated hospitals, U.S. Army, and institutions in Germany and Korea — sought a technique for non-invasively monitoring healing progress of severe wounds, such as burns and ischemic wounds, where blood flow to the injury is blocked. Chronic wounds of this kind, including those caused by combat, are estimated to affect 6.5 million people in the U.S., leading to some $25 billion in health care costs each year.
The bandage technology measures the extent of oxygen concentration in the wound area, an indicator of the extent of healing. It uses porphyrin-dendrimer materials, called Oxyphor R2 made by Oxygen Enterprises in Philadelphia, that give off a phosphorescent glow in the presence of oxygen. The bandage compound also has a green dye that acts as a baseline reference and with which clinicians can measure the extent of healing as it changes to red.
The bandage is painted on the wound as a viscous liquid using as its base New-Skin liquid bandage, an over-the-counter product made by Prestige Brands that dries to a solid film. A transparent barrier layer is then applied over the film to keep out ambient air, thus responding to oxygen concentrations generated as a result of the healing process.
The third part of the technology is a camera-like device that first gives off light to excite the phosphors in the porphyrin-dendrimer materials, and then measures the light emissions from the bandage. Zongxi Li, a research fellow in Evans’s lab and first author of the paper, says in an Optical Society statement that the camera can be configured to “measure either the brightness or color of the emitted light across the bandage or the change in brightness over time.”
The researchers tested proof-of-principle technology to measure burn healing in lab rats and pigs, as well as a monitor for healing of skin grafts with pigs. The lab plans to extend the bandage’s sensory capabilities to other healing indicators such as pH and bacterial load, as well as adapting the technology to on-demand release of drugs.
Evans and colleagues are seeking industry partners to bring the technology to market. One potential application is hand-held or smartphone-based field devices, since the light emitted from the bandage is bright enough to be read by those systems.
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1 October 2014. Medical and materials scientists at Tel Aviv University in Israel designed a heart tissue repair patch that adds in gold nanoparticles to improve electrical signaling and muscle performance. The team from the lab of life sciences professor Tal Dvir published its findings last month in the journal Nano Letters (paid subscription required).
The researchers aim to build on previous work engineering tissue patches to repair damage from heart attacks. Heart muscle does not easily repair itself, requiring a collagen structure from outside the heart on which new tissue can develop. Heart cells from the patient can then grow on that structure into new muscle that responds to electrical signals and contracts like the original.
Experiments with synthetic matrices or scaffolds up to now use decellularized collagen from pigs that approximates human tissue, but residual sugar and other cells on the collagen matrix can trigger an immune response and rejection by the recipient. Instead of a scaffold made of animal collagen, the Tel Aviv team harvested fatty tissue from an individual’s abdomen for the scaffold, which removes the chance for an immune response and rejection.
A drawback of harvested abdomen tissue for the scaffold, however, is its limited ability to establish a network for electrical signals like that found in original heart tissue. “Biomaterial harvested for a matrix,” says Dvir in a university statement, “tends to be insulating and thus disruptive to network signals.”
To improve electrical conductivity of the engineered tissue, the researchers deposited gold nanoparticles on the surface of the harvested matrix. Engineered heart tissue with the gold nanoparticles, say the authors, develops connexin 43 electrical coupling proteins that form signaling channels and allow for coordinated contraction of heart muscles. Tests show adding the the gold nanoparticles enables the engineered heart tissue to transmit electrical signals faster and more efficiently than the same tissue without the added gold.
The Tel Aviv team conducted preliminary tests with the engineered heart tissue on lab animals with positive results. They next plan to extend the tests to larger animals and eventually to human clinical trials.
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Respiratory syncytial virus (NIH.gov/NIAID)
30 September 2014. The biotechnology company Alios BioPharma Inc., a developer of anti-viral medications, is being acquired by health care products enterprise Johnson & Johnson for $1.75 billion. The all-cash deal will add Alios BioPharma’s pipeline to the portfolio of Janssen Pharmaceuticals, a division of Johnson & Johnson.
Alios BioPharma, in South San Francisco, California, develops therapies for viral diseases from its library of nucleoside analogs, compounds designed to act like derivatives of nucleic acids that block the assembly of genetic molecules, thus preventing the replication of the virus. Nucleoside analogs are the basis of therapies for a range of diseases including various types of cancer and bacterial infections, as well as viral infections.
The company’s lead candidate, code-named AL-8176, is a nucleoside analog treatment for respiratory syncytial virus, or RSV, that infects lungs and breathing passages, for which there is not yet a cure. Among children under 1 year of age, RSV is the most common cause of bronchiolitis — inflammation of small airways in the lungs — and pneumonia. Centers for Disease Control and Prevention says between 75,000 and 125,000 children in the U.S. are hospitalized for RSV each year.
In July, Alios BioPharma released initial results of an intermediate-stage clinical trial of AL-8176, where healthy volunteers were infected with RSV, then treated with one of 3 dose levels of AL-8176 or a placebo for 5 days. The company says the trial met its primary objective of lower viral loads among the infected patients taking AL-8176 compared to the placebo. By day 12, none of the patients treated with AL-8176 had detectable RNA from the RSV virus in their systems, while RNA was still evident in the patients receiving the placebos.
Alios is recruiting participants for a trial of AL-8176 among infants hospitalized with RSV, at sites outside the U.S. The company is also developing therapies for the common-cold virus (rhinovirus), influenza, and hepatitis C.
Janssen Pharmaceuticals, a division of Johnson & Johnson, is expected to add the Alios pipeline to its current research and development of treatments for infectious diseases including HIV/AIDS, hepatitis C, and tuberculosis.
Hat tip: FirstWord Pharma
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(National Institutes of Health)
29 September 2014. EnteroMedics Inc., a medical device developer in St. Paul, Minnesota, says marketing approval in Europe for its vagus nerve blocking device for obesity is extended to cover type 2 diabetes. A CE Mark, which signifies approval to market regulated products such as medical devices in the European Union and associated countries, is expanded in this case for EnteroMedics’ Maestro Rechargeable system.
EnteroMedics develops devices to treat obesity and metabolic disorders by blocking vagus nerve signaling between the brain and stomach. The vagus nerve extends from the brain to the abdomen, through the esophagus, lungs, and heart, and is part of the involuntary nervous system controlling various bodily functions including digestion.
The company’s technology, called Vbloc, controls signaling along the vagus nerve, targeting perceptions of hunger and fullness that respond to expansion of the stomach and contractions of stomach muscles. Blocking these signals is believed to help individuals better control their appetite and food intake, thus encouraging weight loss. These same signals are also believed to affect secretion of digestive enzymes and blood glucose levels.
The Maestro Rechargeable system incorporates Vbloc technology in a device about the size of a heart pacemaker implanted in the abdominal region. EnteroMedics tested the Maestro system in a clinical trial with 28 obese patients also with type 2 diabetes, over a 3-year period, and reported initial findings last month at a meeting of the International Federation for the Surgery of Obesity and Metabolic Disorders.
After 3 years, patients with the device reported a decrease in blood sugar (glycated hemoglobin) and fasting blood glucose levels, as well as lower body weight compared to baseline measures. In addition, patients with the Maestro device reported improvements in blood pressure among those having hypertension at the beginning of the trial.
The Maestro device is not yet approved in the U.S. However, EnteroMedics is testing the device in a late-stage clinical trial among 234 obese patients, including those with type 2 diabetes, in the U.S. and Australia, where participants receive either a Maestro device blocking vagus nerve signals or a sham device not blocking the signals. Initial results reported earlier this month show patients receiving the Maestro device had more weight loss than patients with the sham device, but the amount of weight loss between the groups, while statistically reliable, did not meet the study’s target of a 10 percentage-point difference.
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Induced pluripotent stem cells cluster (National Institute of Neurological Disorders and Stroke)
29 September 2014. ReproCell Inc., a developer of stem cell lines for research and therapies in Yokohama, Japan, is starting an investment fund that aims to back new biotechnology companies bringing stem cell research to market. The fund, called Cell Innovation Partners, begins with ¥800 million ($US 7.3 million) in capital, provided by Shinsei Corporate Investment Limited, a division of Shinsei Bank in Tokyo.
Cell Innovation Partners plans to support enterprises developing commercial products and services based on research in induced pluripotent stem cells and regenerative medicine. Induced pluripotent stem cells are adult stem cells, genetically reprogrammed to a similar state as embryonic stem cells, expressing genes and factors that enable them to grow and transform into various cells in the body. While basic research on regenerative medicine from induced pluripotent stem cells continues, they have already shown value as tools for drug discovery, development, and testing.
In a discussion on the fund’s Web site, ReproCell’s CEO Chikafumi Yokoyama says the market for regenerative medicine is expected to grow substantially and new companies in the field are being formed, but “in reality, sufficient risk money is not available to stem cell and regenerative medicine venture companies both domestically and overseas.” Cell Innovation Partners, says Yokoyama, aims to provide financing for companies in the U.S. and Europe, as well as Japan, commercializing these technologies.
In the partnership, ReproCell says it brings expertise in stem call science and biotechnology industry, while Shinsei Corporate Investment provides its finance and fund management experience. Cell Innovation Partners expects to evaluate funding candidates by not only their scientific bases and intellectual property, but also their business models and plans. Shinsei Corporate Investment’s CEO Ippei Matsubara says the candidate’s growth potential over the next 5 to 7 years, competitive advantages, and leadership will also be assessed.
ReproCell was founded in 2003 to commercialize research in stem cells by Norio Nakatsuji at Kyoto University and Hiromitsu Nakauchi at University of Tokyo. The company provides reagents for research on stem cells, as well as stem-cell derived precursors for heart, liver, and brain cells. ReproCell also provides animal cell models for diabetes research.
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26 September 2014. A clinical trial of more than 500 patients shows a lower-dose formulation of a current medication reduces eye pain and inflammation among more post-surgical cataract patients than a placebo. Bausch and Lomb, a subsidiary of Valeant Pharmaceuticals in Laval, Quebec, Canada, reported today results of the late-stage clinical trial.
The trial tested a lower concentration of Bausch and Lomb’s drug Lotemax, prescribed to relieve inflammation and pain following surgery on the eyes. Lotemax is a form of the corticosteroid compound loteprednol etabonate, currently administered as a gel in concentrations of 0.5 percent. The study tested Lotemax in a concentration of 0.38 percent, which the company says was possible because of sub-micron particles — less than 1 millionth of a meter — that in preclinical tests were able to get greater penetration than the standard formulation.
For the clinical trial, Bausch and Lomb enrolled 514 patients who underwent cataract surgery without complications and who experienced between 6 and 15 white blood cells in the anterior chamber, part of the eye between the cornea and iris, an indicator of inflammation following surgery. Patients were recruited at 47 sites in the U.S.
Enrolled patients were randomly divided into four groups: two groups receiving the lower concentration of loteprednol etabonate gel 2 or 3 times a day for 14 days, and two other groups using a placebo ointment — in this case, the same gel but without the drug mixed in — also 2 or 3 times a day for 14 days. Patients were assessed after day 7, half way through the study period, where researchers looked primary for removal of all anterior chamber cells and reports of no pain (grade-0) on a standard chronic pain scale. Researchers also looked for evidence of cells in the anterior chamber and grade-0 pain reports after day 14, as well as problems related to the anterior chamber.
The company reported findings that show more patients using the lower-concentration ointment either 2 or 3 times a day experience complete removal of anterior chamber cells as well as report no pain after day 7, than their counterparts receiving the placebo. After day 14, more patients continue to report removal of all anterior chamber cells and grade-0 pain in the eyes. In addition, the need for rescue medication is higher among placebo patients. While safety issues were not part of the trial, the company says no safety problems were reported.
Bausch and Lomb is planning a second clinical trial, comparing effectiveness of the lower-concentration Lotemax ointment given twice a day compared to a placebo; that trial is not yet accepting patients. The company plans to file a new drug application with the U.S. Food and Drug Administration in the second half of 2015 based on results of these studies.
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Hydrogen and oxygen gas generated by water-splitting solar-powered electrodes (Alain Herzog, EPFL)
26 September 2014. Engineers at Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland designed a solar energy system made of inexpensive and abundant materials that efficiently splits water into hydrogen and oxygen for producing electricity. The team from the lab of EPFL’s Michael Grätzel, with colleagues from Singapore and Korea, published its findings in today’s issue of the journal Science (paid subscription required).
Producing energy from the sun is a longstanding goal of scientists, business people, and policy makers eager for alternatives to fossil fuels that create greenhouse gases as well as economic dependence on hostile or unstable parts of the world. Developing energy systems that harness the sun, however, are hampered by continuing challenges of cost, efficiency, scalability, and storage for times when sunlight isn’t available.
The researchers led by postdoctoral researcher Jingshan Luo devised a system combining solar cells made of the perovskite, a calcium-titanium oxide mineral, with electrodes made of inexpensive metals. Perovskite is attracting increasing scientific and industrial interest as an alternative to silicon in photovoltaic solar cells, with new companies being formed to commercialize advances in the technology.
The system designed by Luo and colleagues simulates the photosynthesis process in plants, converting energy from the sun into a chemical fuel, in this case hydrogen. The solar cells built from perovskite produce an electric current, with the system using that current to split water into its hydrogen and oxygen components. The hydrogen produced by the system can then be captured and stored for fuel cells that generate electric power on demand, with water their only byproduct.
Most water-splitting systems up to now require platinum as a catalyst in electrodes to generate an electrochemical reaction that releases hydrogen and oxygen. Platinum, however, is expensive and Grätzel’s lab is working on finding alternatives as catalysts in energy systems. For this system, the EPFL team tested electrodes made of various materials, but found nickel-iron hydroxides deposited in foam layers got the best results, comparable to platinum. The foam configuration provided more surface area for the catalyst than a smooth surface.
The researchers wired two perovskite solar cells hooked to the nickel-iron electrodes, in series and in close proximity, in an aqueous alkaline solution. The team needed 2 solar cells to generate enough current, about 10 milliamperes per square centimeter, to power the system, although 3 or more silicon-based solar cells are usually needed for that output, say the authors. In lab tests, the team found the system produces hydrogen gas with a solar-to-hydrogen efficiency of 12.3 percent.
The system still has some drawbacks, say the researchers. The perovskite solar cells degrade after a few hours, and greater efficiencies are probably achievable with a more integrated system. Because perovskite solar cells are rapidly developing greater capacity and performance, the authors believe greater energy output and stability are feasible.
Luo tells more about the EPFL system in the following video.
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Science and Enterprise is taking off on Thursday, 25 September to observe Rosh Hashanah, the Jewish new year. We wish everyone of any faith or without, a happy and healthy new year, 5775 in our calendar. We will resume regular posting on Friday.
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24 September 2014. ImmunoCellular Therapeutics Ltd., a developer of cancer therapies harnessing the immune system, is licensing technology developed in the lab of David Baltimore at California Institute of Technology in Pasadena that derives cancer-fighting cells from a person’s own blood-forming stem cells. Financial terms of the exclusive license to ImmunoCellular Therapeutics, based in Los Angeles, were not disclosed.
David Baltimore is president emeritus of Caltech and shared the 1975 Nobel Prize in Physiology or Medicine. Baltimore’s lab is conducting basic research in genomics, as well as translational research on reprogramming the human immune system with gene transfer techniques. Among the translational research are studies of adapting an individual’s hematopoietic or blood-forming stem cells to create cancer-fighting T-cells from the immune system, the focus of the license.
ImmunoCellular’s work up to now encompasses therapeutic vaccines for cancer addressing dendritic or antigen-presenting cells that induce a response from T-cells in the immune system. The company’s pipeline includes an experimental therapy for newly diagnosed glioblastoma multiforme, a highly malignant and deadly brain cancer, in intermediate-stage clinical trials, while a treatment for recurrent glioblastoma is in early-stage trials. A third therapy for ovarian cancer is still in preclinical development.
The Baltimore lab technology is expected to complement ImmunoCellular’s current cancer therapies. A continuing challenge in some cancer immunotherapies is the short duration of their effectiveness. The technology obtained through the license adds T-cell receptors to blood-forming stem cells rather than into T-cells themselves. The result, says the company, is a longer-lasting immune response that can treat previously unresponsive solid-tumor cancers, as evidenced in research with lab animals by Caltech and others.
“Our goal,” says ImmunoCellular CEO Andrew Gengos in a company statement, “is to generate a first clinical candidate from this new discovery platform, and expand our existing dendritic cell expertise into the adjacent fields of stem cells and T-cells.” The company says it expects to develop therapies that can work as single agents or in combination with other treatments.
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Kevin Kit Parker (Harvard University)
24 September 2014. Biomedical engineers at Harvard University developed a model of human airway muscles on a miniaturized chip that emulates their actions during an asthma attack. The senior author of the paper describing the airway muscles chip, Kevin Kit Parker, is also a recipient of a new National Institutes of Health grant to develop a chip emulating cardiopulmonary systems, one of 11 awards announced yesterday to advance tissue-chip devices for drug screening.
The human airway muscles emulation chip is described in a recent issue of the journal Lab on a Chip (registration required), where Parker and colleagues built the model as a tool to better test asthma drugs, which often have limited success in human clinical trials. Among the problems facing asthma drugs in trials are the differences in respiratory anatomy between lab animals and humans, and the complex and variable nature of asthma, which makes it difficult to find a single drug that can treat the disease.
Asthma is chronic condition, where the airways become inflamed and narrow, causing people with asthma to experience wheezing, shortness of breath, tightness in the chest, and coughing for periods of time. Centers for Disease Control and Prevention estimates that in 2010 some 18.7 million adults had asthma, along with 7 million children.
The chip is made of engineered smooth bronchial muscle tissue in an elastomer-polymer material, arrayed in layers on a glass surface to simulate construction of airways. The researchers submitted the airway chip to interleukin-13, a protein found in the airways of people with asthma.
The team then introduced acetylcholine, a neurotransmitter that signals muscles to contract, which caused the simulated airway muscles to rapidly tighten, as happens during an asthma attack. When exposed to drugs that cause muscles in the airway to relax — beta agonists and muscarinic antagonists — such as those found in inhalers often used by people with asthma, the muscles on the chip relaxed. Tests with the chip also showed the researchers could calibrate muscle contractions on the chip by varying doses of the drugs.
In addition, the team looked into properties of cells in muscle tissue on the airway chip. The researchers found the presence of interleukin-13 causes a greater alignment of actin filaments, which help form the structure of cells, resulting in enlargement of smooth muscle cells, a characteristic of muscles in airways of people with asthma. The team exposed the airway chip to a drug known as HA-1077, a compound used to widen blood vessels by inhibiting smooth muscle contractions, which targets a cell signaling pathway addressing actin fibers.
Tests with HA-1077 show the drug, not currently used to treat asthma, makes tissues on the airway muscle chip less sensitive to signals that trigger muscle contractions associated with asthma. The researchers reported early evidence that the combination of HA-1077 and asthma drugs worked better with airway muscles on the chip than asthma drugs alone.
NIH awards for tissue chip development
National Institutes of Health yesterday announced 11 recipients of grants to develop chip devices that emulate human organs and tissues that can eventually be linked together to simulate complex whole body functions. The program, led by the National Center for Advancing Translational Sciences (NCATS) in NIH, aims to provide alternatives to current methods to test drugs for safety and effectiveness. Funds for the first year of the three-year grants total $17 million.
Parker’s lab in Harvard’s School of Engineering and Applied Sciences was among the recipient’s of the NCATS grants. The award of nearly $1.2 million supports development of an integrated model of the human cardiopulmonary system. Among the reasons for failure of some drugs in late-stage clinical trials is toxicity to the heart, and the device to be developed aims to emulate human heart and lungs in both healthy and diseased states to test drugs for toxicity before trials with humans.
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