(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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23 September 2014. A clinical trial is underway testing the safety of a new therapy designed to treat addictions and compulsive behavior by Savant HWP, a drug development company in San Carlos, California. The study is testing the compound 18-methoxycoronaridine or 18-MC, conducted in South America by a Brazilian partner company identified as Hebron Farmaceutica S.A.
The compound 18-MC is a synthetic version of ibogaine, a plant-based medicine believed to have properties that can relieve addictions, but without the toxicity associated with natural ibogaine compounds. 18-MC addresses the reward pathways, where fluctuations in dopamine drive pleasure-seeking behavior, and seeks to control the underlying addictive mechanism in the brain. Most other addiction-control treatments target receptors of the addictive compounds, like methadone as a substitute for heroin.
Research by Stanley Glick, a professor emeritus at Albany Medical College in New York, shows 18-MC can reduce addictive behavior associated with cocaine, methamphetamine, morphine, nicotine, and alcohol in lab animal tests, where the animals self-administer the addictive substances. Glick is one of the founders of Savant HWP that licenses the intellectual property from Albany and other institutions collaborating with Glick. Savant HWP’s development of 18-MC as a commercial compound is funded by a $6.5 million grant in 2013 from National Institute of Drug Abuse, part of National Institutes of Health.
The trial is testing a single dose 18-MC in a double-blind, placebo-controlled study among healthy volunteers. A story from June 2014 in the Albany Times-Union says the Food and Drug Administration had last minute questions about the sensitivity of some lab animals to 18-MC as an addiction treatment. However, the chemistry in 18-MC also affects molecular pathways addressing the tropical parasitic disease leishmaniasis. As a result, says the newspaper, the trial conducted by Hebron Farmaceutica is testing 18-MC for the drug’s safety, but in the context as a leishmaniasis treatment, not as an addiction treatment.
Savant HWP co-founder and chairman Scott Freeman says in a company statement that initial reports from the trial show the drug is well-tolerated among the volunteer subjects. “Safety and dose-ranging studies are continuing,” adds Freeman, “and we expect to present detailed results at medical meetings and in scientific publications at the conclusion of the trial.”
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Ebola health care workers in Guinea (European Commission-ECHO/USIAD)
23 September 2014. Tekmira Pharmaceuticals Corp. says the U.S. Food and Drug Administration approved the company providing its experimental therapy for people with suspected or confirmed Ebola infections. The Vancouver, British Columbia biotechnology company says approval of its therapy called TKM-Ebola is part of a larger regulatory framework for the treatments worked out with FDA and Health Canada, its counterpart agency.
Tekmira develops therapies based on small interfering RNA, synthesized molecules that suppress the production of proteins causing disease. RNA is a nucleic acid related to DNA that generates the protein-making instructions from an individual’s genomic code. Small interfering RNA attaches to the RNA signals, called messenger RNA, and blocks the production of the disease-causing proteins.
The company says these small interfering RNA target specific messenger RNA molecules, and can continue working in the body to prevent further production of those disease-causing proteins. To aid this process, Tekmira also developed a lipid nanoparticle delivery system for its interfering RNA that encapsulate the therapeutic molecules in natural nanoscale fats or oils, which allows disease site cells to accumulate and then interact with the cells to release the treatments.
in 2010, Tekmira received a contract from the U.S. Defense department to advance a therapy for an earlier (Zaire) strain of Ebola that the company showed could protect non-human primates from infection. The contract was expanded 3 years later to include improvements in its lipid nanoparticle delivery system allowing for freeze-dried formulations and administrations of the drug with injections under the skin.
In January 2014, Tekmira began an early-stage clinical trial of TKM-Ebola among healthy subjects for safety and chemical activity in the body. In March, FDA approved a fast-track designation for TKM-Ebola that expedites regulatory review of the treatments. The company says FDA is allowing development of TKM-Ebola under its so-called animal rule that permits consideration of marketing approval for therapies based on tests with animals, in cases where human trials are infeasible or unethical.
The new regulatory framework, says Tekmira, comes under FDA’s expanded access program that allows early use of experimental drugs outside of clinical trials, where there are no comparable or satisfactory treatment options. While that authority is usually granted on a case-by-case basis, it can also be extended to smaller groups of people before the safety of the new therapy is established, and to larger groups once the drug’s safety is known.
Tekmira’s CEO Mark Murray says in a company statement TKM-Ebola was given to “a number of patients” and was well tolerated, even with repeated infusions. “However,” Murray adds, “it must be kept in mind that any uses of the product under expanded access, does not constitute controlled clinical trials. These patients may be infected with a strain of Ebola virus which has emerged subsequent to the strain that our product is directed against, and physicians treating these patients may use more than one therapeutic intervention in an effort to achieve the best outcome.”
The company says as well it is collaborating with a consortium to expedite clinical trials of Ebola treatments in West Africa that includes World Health Organization, University of Oxford, Institut Pasteur, and several non-government organizations. The initiative, announced today, is funded by a £3.2 million ($US 5.2 million) grant from the Wellcome Trust. A group of experts from WHO is evaluating potential Ebola treatment candidates for the trials, including those made by Tekmira.
Hat tip: FirstWord Pharma
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Sickle cell test sample (A. J. Kumar, Harvard University)
22 September 2014. A Cambridge, Massachusetts diagnostics company received a Small Business Innovation Research (SBIR) grant to develop a simple point-of-care test for sickle cell disease, a genetic blood disorder affecting a large percentage of people of African origin. The $225,000 grant from National Institutes of Health’s SBIR program to Daktari Diagnostics will support development and testing of a commercial prototype of the sickle cell diagnostic, in partnership with Harvard University, University of South Carolina, and University Teaching Hospital in Lusaka, Zambia.
Sickle cell disease is a genetic blood disorder affecting hemoglobin that delivers oxygen to cells in the body. People with sickle cell disease have hemoglobin molecules that cause blood cells to form in an atypical crescent or sickle shape. That abnormal shape causes the blood cells to break down, lose flexibility, and accumulate in tiny capillaries, leading to anemia and periodic painful episodes. The disease is prevalent worldwide, and affects 70,000 to 80,000 people in the U.S., including about 1 in 500 people of African descent.
Newborns in the U.S. are tested routinely for sickle cell disease, but not in many areas where resources are limited, including many places in Africa. Daktari Diagnostics develops medical tests for resource-limited regions, combining microfluidics (lab-on-a-chip) technologies with electrochemical sensing, which the company says are designed to be simple, portable, and inexpensive.
The grant — from NIH’s National Heart, Lung, and Blood Institute — supports development of a commercial prototype based on a device designed in the lab of Harvard chemistry professor George Whitesides by then-graduate student A. J. Kumar. The system devised by Kumar and colleagues harnesses a principle in chemistry that polymer chemicals separate into different layers when mixed with water. The team applied that idea to separating red blood cells of different densities in a mix of polymers and water.
Kumar, now a postdoctoral researcher in the Whitesides lab and the lead engineer on Daktari’s project, tested an early version of the device as a proof-of-concept exercise, with the results published earlier this month in the journal Proceedings of the National Academy of Sciences. The device basically consists of a narrow tube with a mix of water and polymers, where a drop of blood is drawn with a finger prick that wicks into the tube. Spinning the tube on a standard lab centrifuge separates the multiphase blood-polymer-water mixture into visually discernible layers, with the heavier sickle cells sinking to the bottom, all in about 12 minutes.
For the commercial prototype Daktari aims to develop a device with tubes designed for a simple, battery-powered centrifuge, pre-filled with the polymer-water mixture. Blood samples would be taken with a finger-prick or a heel-stick from newborns. If sickle cells are present in the blood, they will sink to a designated region in the tube, where technicians can easily identify them. As with the proof-of-concept, Daktari is aiming to have the commercial test return results in about 12 minutes.
A key part of the proposed commercial system is the simple battery-powered centrifuge to separate the blood-water-polymer mixture into layers. Daktari says it plans to apply its experience with a battery-powered, hand-held device to measure CD4 T-cells in blood as part of an HIV test.
Daktari says the test is called Mpana, an acronym for MultiPhase Analyzer, but also a Swahili word for ” a broad, wide, open channel.” The grant funding covers work on the device through May 2015, although the project is expected to continue through May 2016.
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