Kari Nadeau (Stanford University)
28 February 2014. Medical researchers at Stanford University in California and Johns Hopkins University in Baltimore found in an early-stage clinical trial that an asthma drug dramatically reduces the time needed for patients to lower their sensitivity to several food allergies at one time. The team led by Stanford’s Kari Nadeau and Johns Hopkins’s Robert Hamilton published its findings online yesterday in the journal Allergy, Asthma & Clinical Immunology.
Nadeau, Hamilton, and colleagues cite studies from the past three years showing 8 percent of children in the U.S. have a food allergy, with 30 percent of that group reporting allergies to more than one food. Food allergies in the U.S. are estimated to cost $25 billion, mainly from lost work time, changing careers, and emergency room visits, with that cost borne largely by families. People with food allergies are advised to avoid allergy triggers and always carry injectable epinephrine because of the risk of anaphylactic shock from accidental consumption.
This study is the second in a series of clinical trials on multiple food allergies. Many of the same Stanford/Johns Hopkins researchers published its earlier findings in the same journal on 15 January 2014. In that study, the researchers showed patients with several food allergies could be desensitized at once to several multiple foods causing an allergic reaction, rather than going through the process sequentially for each food.
In that process, called oral immunotherapy, patients with food allergies eat small amounts of the offending foods, gradually increasing the amounts they eat in a controlled setting and under a doctor’s supervision. In the earlier study, 25 patients allergic to peanuts and to at least one of other types of foods — sesame, other nuts, dairy, or egg — underwent oral immunotherapy. The researchers found the rates of allergic reactions to the multiple offending foods in this group of patients, was similar to a group of 15 patients with only a peanut allergy, also receiving oral immunotherapy.
In the later study, 25 children and adults with food allergies were first given the drug omalizumab, developed to reduce the number of allergic asthma attacks, those caused by environmental allergens, such as dander, pollen, and dust mites. Omalizumab, marketed as Xolair by Genentech and Novartis, reduces activity of imunoglobulin E (IgE), a type of antibody that binds to allergens and triggers the release of substances from mast cells — tiny cells with chemicals causing inflammation.
Eight weeks after omalizumab injections, the 25 patients underwent an oral immunotherapy regimen for multiple offending foods similar to the earlier trial group. The results show 19 of 25 patients receiving omalizumab injections were able to complete the six stage oral immunotherapy process, with little or no need for rescue therapy.
Patients receiving omalizumab were able to tolerate up to four grams each of the offending foods, in powdered protein form, in a median period of 18 weeks. Patients in the earlier trial of oral immunotherapy, without the omalizumab, needed a median of 85 weeks to become desensitized to the offending foods.
The trials’ main objective was to test for the safety of oral immunotherapy, both with and without omalizumab. In the earlier study, most reactions to the allergens were mild, although two severe reactions were reported each in the peanut-only and multiple-foods groups requiring epinephrine injections. In the later study, with omalizumab, 94 percent of reactions were considered mild, with one severe reaction reported.
Nadeau and colleagues are now planning for an intermediate-stage clinical trial at Stanford and four other sites.
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28 February 2014. Abingworth LLP, an investment company based in London, closed its 10th fund designed for financing life sciences and health care enterprises. The company says its Abingworth Bioventures VI fund raised £225 million ($375 million), exceeding its target of £200 million.
Abingworth expects its Bioventures VI fund to invest in life sciences companies in Europe and the U.S., making 15 to 20 transactions ranging in size from £5 to £20 million ($8 to $33 million). The company says the fund plans to make early and late stage venture and growth-capital deals in privately owned, as well as selected public companies, known as Venture Investments in Public Equities or Vipes.
The Bioventures VI already closed four deals, two of which are in the U.S.:
- Avedro Inc. in Waltham, Massachusetts, developing corneal collagen cross-linking therapies to treat eye disorders, such as keratoconus causing visual distortions and post-Lasik ectasia or thinning of the cornea.
- Avillion LLP in London, that funds and manages late-stage clinical trials for regulatory drug approvals
- eFFECTOR Therapeutics in San Diego, developing small-molecule drugs as cancer treatments
- GenSight Biologics in Paris, a developer of gene therapies for degenerative retinal disorders
In addition to pharmaceutical and biotechnology companies, Abingworth also invests in companies designing medical devices, instrumentation, and health services. Abingworth says it brings to its portfolio companies legal, investment banking, operating and recruiting capabilities, and can call on a network of scientific and industry consultants.
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AllSee prototype attached to smartphone (University of Washington)
27 February 2014. Computer scientists and engineers at University of Washington in Seattle developed an inexpensive gesture recognition system for mobile devices that consumes minimal power, with potential applications in robotics and “Internet-of-things” computing. The team led by Shyam Gollakota, director of the university’s Networks and Wireless Lab, presents its work on 3 April at the USENIX Symposium on Networked Systems Design and Implementation in Seattle.
The system, known as AllSee, uses a small sensor with a receiver requiring minimal power. The sensor and receiver take advantage of ambient wireless signals in the environment, such as television signals, that are detected and harnessed. Hand gestures change the amplitude of the wireless signals, and when they occur near the sensor, the AllSee system captures and recognizes the changes in signal amplitude, which it transforms into commands for the host device.
AllSee sensors, say the researchers, use three to four times less power than current gesture-recognition systems, like those developed for the Samsung Galaxy S4 smartphone. Because of their power needs, however, current gesture-recognition systems can quickly drain a smartphone’s battery. Current systems must also be manually switched on and in direct line-of-sight of their sensors.
The AllSee system, on the other hand, consumes minimal power — tens of microwatts say the developers — and, as a result, can be left on. In addition, the AllSee system can sense changes in wireless signal amplitude even when the attached device is sitting in a pocket or purse. Thus the AllSee can sense hand gestures changing audio levels on the attached phone, for example, without reaching into the pocket or purse.
Gollakota and colleagues tested a prototype AllSee system, with eight different hand gestures such as pushing or pulling to zoom in and out, on smartphones and battery-free sensors. They found the prototype could identify the gestures more than 90 percent of the time, with the gestures occurring as far as two feet away.
The researchers report a response time of less than 80 milliseconds, about 1,000 times faster than a blinking eye. They also devised a procedure using a finger-flick motion as a starting sequence to discriminate between AllSee commands and normal hand gestures.
“This is the first gesture recognition system that can be implemented for less than a dollar and doesn’t require a battery,” says Gollakota in a university statement. The researchers say the technology can also be applied beyond mobile devices to robotic systems and with Internet-enabled household devices and monitors — i.e., Internet of things — where hand gestures can control their actions and movements without a large added power drain.
The following video demonstrates the AllSee prototype.
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(National Cancer Institute)
27 February 2014. The global pharmaceutical company Eisai Inc. is starting a late-stage clinical trial of its drug eribulin mesylate to treat certain types of recurring or metastatic breast cancer, compared to the current chemotherapy drug paclitaxel. The trial is a joint project of Eisai’s U.S. subsidiary, in Woodcliff Lakes, New Jersey, and Academic and Community Cancer Research United, a clinical research network based at the Mayo Clinic in Rochester, Minnesota. Eisai’s headquarters is in Tokyo.
The study aims to enroll 910 patients with HER2-negative locally recurrent or metastatic (spreading) breast cancer, having no more than one previous course of chemotherapy. Human epidermal growth factor receptor 2 or HER2 genes generate proteins that regulate breast growth. The over-expression of those proteins contributes to uncontrolled growth of breast cells and accounts for about a quarter of breast cancer cases. HER2-negative status indicates HER2 genes are not over-expressing and thus not contributing to the cancer’s spread.
The trial tests eribulin mesylate, marketed by Eisai as Halaven, against the standard chemotherapy drug paclitaxel, as an initial cancer treatment or as a back-up treatment if the first-line treatment does not work or stops working. The primary effectiveness measure in the trial is overall survival of the patients, while the study will also follow progression-free survival and objective tumor response rate, as well as safety and tolerability of the drugs.
Patients in the trial will be randomly divided between receiving eribulin mesylate or paclitaxel, with both drugs administered as intravenous injections. Eribulin mesylate is given once a week over a three-week period, while paclitaxel is also administered once a week, but over four weeks. Paclitaxel is marketed as Abraxane by Celgene Corp., and also available in generic forms.
Eribulin mesylate is a synthetic form of the natural compound halichondrin B, derived from the Halichondria okadai sea sponge. While early lab tests showed the compound’s potential as cancer treatment, extracting sufficient quantities in its natural state proved to be difficult. Research at Harvard University in the 1990s showed it was possible to synthesize the halichondrin B, and Eisai licensed the process which eventually led to development of its Halaven product.
Academic and Community Cancer Research United is recruiting patients for the trial. Only one location — Rochester, New York — is so far identified.
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26 February 2014. Zoetis Inc., an animal health company in Florham Park, New Jersey, is funding grants to researchers for studies into pain, joint health, and kidney disorders in cats. Grants totaling $100,000 will be made available through the Winn Feline Foundation, with a due date for proposals of 21 April 2014.
The company says the grants will support research into biomarkers as indicators of acute and chronic pain in cats, both the adaptive pain of healing tissue and non-adaptive pain, such as neuropathic pain. Studies of osteoarthritis in cats are also sought in the proposals, including those investigating causes and progression of the disorder, as well as related biomarkers.
In addition, Zoetis and Winn Feline Foundation are seeking proposals identifying biomarkers of chronic kidney disease, both systemic and urinary biomarkers. The funders say there’s an urgent need for early detection methods for kidney disorders.
The Winn Feline Foundation expects to award grants of $12,000 to $35,000 for projects lasting one to two years, although larger undertakings will be considered. Proposals must be submitted in a single document following the foundation’s instructions and are required to include cover page, scientific summary, non-technical abstract, study proposal, timeline, budget, animal involvement justification, references, curriculum vitae of the principal investigators, and consent forms with questionnaires.
If the proposed research is a continuation of a current foundation-funded study, a progress report of that study is also required. The deadline for proposals is 21 April 2014.
Zoetis was previously a division of the pharmaceutical company Pfizer, spun off as a separate animal health enterprise in February 2013. In April 2013, the company awarded grants to researchers at University of Pennsylvania and Johns Hopkins University for basic science studies diagnosing and treating dermatological conditions in dogs and cats.
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26 February 2014. The Walgreens pharmacy chain and University of California in San Francisco are collaborating on new pharmacy services that help patients manage medications to improve their overall health. The company and university are testing this new retail model in a Walgreens store located near the UCSF campus, but financial aspects of the arrangement were not disclosed.
The Walgreens at UCSF store is an undertaking of the university’s medical center and pharmacy school, working with the pharmacy chain, and located across the street from the medical center. The store is one of the Walgreens Well Experience locations that includes a walk-in health clinic and more accessible pharmacists, as well as areas for private consultations with providers.
The project aims to address problems arising from the increased number of medications being taken by patients, as well as problems of medication adherence. According to Centers for Disease Control and Prevention (CDC), some 8 in 10 Americans (82%) take at least one medication, with 3 in 10 (29%) taking five or more medications. Problems with medications leading to adverse drug events result in some 700,000 emergency room visits and 120,000 hospital visits each year. Extra medical costs from adverse drug reactions are estimated by CDC at $3.5 billion each year.
A related problem is the need for patients to keep taking their medications as prescribed. National Consumers League says 3 of 4 Americans do not always adhere to their medication schedules. Some of the potential reasons for this lack of adherence, according to the U.S. Surgeon General, are co-payments, difficulty remembering and managing complex regimens, and poor health literacy.
“Modern medicine has transformed many diseases from urgent, life-threatening conditions into chronic illnesses that can be managed with the right medications,” says Joseph Guglielmo, dean of UCSF’s pharmacy school in a university statement. “But that means more and more patients are juggling multiple prescriptions, with complex instructions, and, in many instances, this complicated medication list is inaccurate and incomplete.”
The campus Walgreens store will provide medication counseling for patients, as well as comprehensive medication reviews, as a standard of care. Pharmacists are expected to help patients create accurate, portable medication lists to take to their health care providers, and keep them up to date. These services aim to decrease drug interactions and encourage patients to take their medications as prescribed.
The expanded role of pharmacists as health care providers is part of a California law that took effect on 1 January 2014. Under that law, pharmacists can perform additional health care services within their profession, such as providing certain medications, monitoring patient health, and adjusting prescriptions if needed.
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Igor Efimov (Washington University, St. Louis)
25 February 2014. Engineers and medical researchers at Washington University in St. Louis and University of Illinois in Champaign used a three-dimensional printer to create a membrane that fits over the heart, with electronic components to monitor its functions. The team led by Washington University’s Igor Efimov and Illinois’s John Rogers published its findings today in the journal Nature Communications (paid subscription required).
The researchers, which include colleagues from Northwestern University, universities of Texas and Alberta, and institutions in China, Korea, and Singapore sought to create a device that could fit snugly over the outer heart wall without the need for adhesives or sutures to hold it in place. The goal of the system is to provide a platform for multiple circuits that can monitor cardiac functions, and if necessary deliver therapy, better than current devices.
Efimov explains that current technologies for treating heart rhythm disorders, such as atrial fibrillation, have two electrodes that are inserted through the veins and contact heart tissue at only one or two points inside the heart chamber. “What we want to create,” says Efimov in a Washington University statement, “is an approach that will allow you to have numerous points of contact and to correct the problem with high-definition diagnostics and high-definition therapy.”
The Washington University-Illinois team designed an elastic soft-plastic membrane that fits over the heart, but must be custom made to exactly match each patient’s heart geometry. The researchers use CT or MRI scans to create an image and determine dimensions of the heart, then apply computational techniques to build a 3-D model. That model is then fed into a conventional 3-D printer that prints the membrane.
Rogers, a materials scientist, developed techniques for transfer printing of circuits on flexible membrane surfaces. In this project, the circuits printed on the membrane are made from silicon, gallium arsenide, and gallium nitride. The researchers reported on physiological tests of the device in the lab with extracted hearts.
In addition to sensor circuits for pH, temperature and mechanical strain, the membrane can also support controllers for electrical, thermal, and optical stimulation. The membrane can support as well a sensor for troponin, a protein released when the heart is damaged, and can serve as an indicator of a heart attack. Tests for troponin, developed by a Washington University colleague, now require a separate blood sample.
The technology need not be restricted to heart functions, says Efimov. “Because this is implantable” he notes, “it will allow physicians to monitor vital functions in different organs and intervene when necessary to provide therapy. In the case of heart rhythm disorders, it could be used to stimulate cardiac muscle or the brain, or in renal disorders, it would monitor ionic concentrations of calcium, potassium and sodium.”
In 2008, Efimov founded Cardialen Inc., a company in St. Louis and Minneapolis that licenses and commecializes discoveries from Washington University, and where he serves as the company’s chief scientific advisor. Rogers is the holder of some 80 patents and founder of several companies commercializing his lab’s research.
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Sangeeta Bhatia (Bryce Vickmark, Massachusetts Institute of Technology)
25 February 2014. Biomedical engineers at Massachusetts Institute of Technology developed and tested with lab mice a simple, inexpensive paper test strip system to diagnose non-communicable diseases. The team led by medical engineering professor Sangeeta Bhatia published its findings online yesterday in the journal Proceedings of the National Academy of Sciences (paid subscription required).
Early detection of disease is highly recommended to improve a patient’s chances of a favorable outcome, but in many places access to imaging equipment used for disease screening, such as mammography, is limited. The MIT team, with colleagues from Harvard Medical School and University of Minnesota, sought a simpler system to detect indicators of non-communicable diseases at the point of care.
Paper strips are being designed to diagnose infectious diseases using fluid samples, such as urine or nasal swabs, for sites with limited access to more advanced technology, and the MIT researchers extend that idea to cover non-communicable diseases. Their approach uses nanoscale particles interacting with biomarkers or indicators of disease in a patient’s urine causing a visible change in the paper test strips.
To release the biomarkers, Bhatia and colleagues coated nanoparticles with protein fragments that target the sites in the body, where diseases are likely to occur. The nanoparticles with protein fragments, known as peptides, are given to the patients. When in the body, the nanoparticles help break loose and bind with the disease biomarkers that then collect in the kidneys and are passed in the urine.
The test strips are coated with various antibodies to first capture the peptides, and then test for the presence of the disease biomarkers. If the antibody lines become visible on the test strips, they indicate the presence of the disease biomarker in the urine. In tests with lab mice, the researchers report the test strips accurately identify colon tumors and blood clots.
The researchers say different antibodies can be placed in lines on the test strips to detect multiple diseases or different stages of a disease. This capability makes it possible to develop a general diagnostic platform for non-communicable diseases, which could be administered by medical staff without extensive training. Results from the tests could be captured with photos of test strips taken by mobile phones, then sent to specialists or filed with medical records.
The next step, say the researchers, is to test the system with human patients. Bhatia and colleagues plan to commercialize the diagnostics, and in October 2013 received a grant from MIT’s Deshpande Center for Technological Innovation to write a business plan for advancing the technology to clinical trials.
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Jonathan Jones (The Sainsbury Laboratory)
24 February 2014. Researchers at The Sainsbury Laboratory in Norwich, U.K. developed and field tested a new type of potato with greater genetically modified resistance to late blight, a long-time scourge of potato growers. The team led by Sainsbury plant biologist Jonathan Jones reported its findings online last week in the journal Philosophical Transactions of the Royal Society B.
Late blight is a plant disease caused by a fungus-like organism, known as Phytophthora infestans, with a long history of destruction, attacking mainly potatoes and tomatoes. The pathogen survives from one season to the next in infected potato tubers, and in wet weather can produce millions of spores from infected plants. Late blight is believed to be the cause of the Irish potato famine of the mid-19th century, and linked to annual crop losses worldwide estimated at $5 billion.
Jones and colleagues from institutes affiliated with Sainsbury Lab developed the new type of potato from the Desiree variety, a popular potato in the U.K. with smooth red skin and yellow flesh. In their original state, Desiree potatoes have hundreds of resistance genes, but the late blight pathogen finds ways of circumventing those barriers.
The researchers found genes from Solanum potatoes, a wild relative of the Desiree in South America that enable the growing of plants to better recognize the late blight invaders and trigger their natural resistance mechanisms. Natural cross-breeding techniques, say the authors, are difficult, slow, and prone to failure. Jones notes in a Sainsbury statement that “by the time a gene is successfully introduced into a cultivated variety, the late blight pathogen may already have evolved the ability to overcome it.”
To create the new transgenic variety, Jones and colleagues isolated the genes with the desirable resistance qualities from Solanum potatoes and introduced them to the Desiree variety. The team then grew transgenic plants for three years in potato fields. Each year, they planted 192 genetically modified plants, and surrounded them with non-modified Desiree and Maris Piper potatoes, another popular variety.
The researchers did not infect the test plants, but instead let the pathogen find the plants on its own. In the last year (2012), the Norwich region experienced a wetter than normal summer, providing ideal conditions for late blight to infect the plants; the previous two years were dryer and thus less favorable to the pathogen.
The trials showed the transgenic plants were completely resistant to late blight and with all of them surviving attacks from the pathogen. Non-modified potatoes, however, were all found infected with late blight. Transgenic varieties also had higher yields of 6 to 13 kilograms of tubers per blocks of 16 plants, compared to 1.6 to 5 kilograms per 16 non-modified plants.
One consequence of the new transgenic potato variety is a reduced need to spray for late blight. The authors say that European farmers spray pesticides on their potato fields as many as 15 times a season to kill late blight, which could be sharply reduced through a strategy of genetic control instead of chemical control.
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Aligned fibroblast nanofibers (Michigan Technological Universtiy)
24 February 2014. Biomedical engineers at Michigan Technological University in Houghton and Duke University in Durham, North Carolina developed a process for creating a framework needed to turn stem cells into engineered regenerative tissue. The research team led by Michigan Tech professor Feng Zhao published its findings online in a recent issue of the journal Advanced Functional Materials (paid subscription required).
Healthy human cells create their own framework structures that organize and build the cells into human tissue. For regenerative medicine, however, that support structure needs to be built separately for cells to populate and grow into new tissue to heal wounds or replace damaged tissue, such as cartilage. Any replacement tissue must also be compatible with the host to reduce the risk of rejection by the body’s immune system.
The problem addressed by the Michigan Tech researchers was to create an organized matrix to support tissue cell growth in the lab with similar properties to natural tissue. Up to now, those structures were based largely on synthetic, not natural, materials or animal substances.
Zhao’s team devised a process for growing fibroblasts — the connective tissue in this supportive matrix — in a controlled lab environment, on a grated surface, some 130 nanometers in depth. The fibroblasts derived from human skin cells were grown as nanoscale fibers, about 80 nanometers in diameter, highly uniform in size and in close alignment, over 8 weeks.
The researchers also were able to seed the resulting matrix with adult stem cells derived from bone marrow that can be transformed into a range of human tissues including muscle, bone, tendon, and cartilage. Since the synthetic fibroblasts were grown originally from human skin tissue, they retained the same supporting complex molecular functions, in addition to providing a place for the cells to grow.
Zhao and colleagues tested the scaffolding for potential rejection by the host if transplanted into a patient. The researchers exposed the lab-generated scaffold to immune system cells associated with inflammation, and compared the response to fibroblast fibers on their own and not in a scaffold. The tests show the scaffold generated significantly fewer inflammatory proteins than the unaligned and unorganized fibroblasts.
“The material they made is quite uniform, and of course it is completely biological,” says Zhao in a university statement. “I think we could use this to engineer softer tissues, like skin, blood vessels and muscle.”
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