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FDA Approves Antibody Treatment for Lung Cancer

Lungs illustration

(National Cancer Institute)

25 November 2015. U.S. Food and Drug Administration yesterday approved necitumumab, an engineered antibody to treat squamous non-small cell lung cancer that spreads to other parts of the body. Necitumumab is marketed under the brand name Portrazza by Eli Lilly and Company.

Worldwide, lung cancer causes some 1.6 million deaths, according to World Health Organization. Non-small cell lung cancer is the most common form of lung cancer, accounting for about 85 percent of all cases. American Cancer Society estimates more than 221,000 new cases of lung cancer will be diagnosed in the U.S. during 2015, affecting somewhat more men than women, leading to 158,000 deaths.

Squamous cell lung cancer begins in thin squamous cells in respiratory tracts. The company cites data showing squamous non-small cell lung cancer that metastasizes, or spreads to other parts of the body is difficult to treat, and metastasizing cancer has less than a 5 percent survival rate over 5 years.

Portrazza is a monoclonal antibody, a biologic drug designed to address specific disease-causing proteins, in this case the epidermal growth factor receptor or EGFR, which when mutates sends signals that encourage tumor growth in the lungs. The drug acts by blocking the ability of EGFR proteins to bind to their target sites, and thus preventing the signals that promote tumor cell proliferation.

FDA based its approval in part on results of a late-stage clinical trial with nearly 1,100 participants, where individuals having metastasizing squamous non-small cell lung cancer were given two chemotherapy drugs — gemcitabine and cisplatin — then randomly assigned to receive Portrazza or continue with chemotherapy alone. Participants receiving Portrazza plus chemotherapy survived for 11.5 months on average, compared to 9.9 months for those receiving chemotherapy alone.

The drug is approved for patients who have not received other treatments for lung cancer. In addition, the approval only covers Portrazza’s use with the same two chemotherapy drugs, gemcitabine and cisplatin, evaluated in the clinical trial.

Portrazza will be marketed with a boxed warning of treatment risks, including cardiac arrest and sudden death, as well as a magnesium deficiency that can cause muscular weakness, seizure, and potentially fatal irregular heartbeats. During the drug’s development, FDA granted Portrazza orphan drug designation for therapies designed to address rare conditions or disorders.

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Crop Disease Images Collected, Available Via Smartphones

PlantVillage images

PlantVillage images show a healthy tomato leaf, upper left, next to leaves with symptoms of disease. (David Hughes, Pennsylvania State University)

25 November 2015. A team in the U.S. and Switzerland is assembling a database of 50,000 images of plant diseases for a smartphone app to help farmers worldwide deal with those diseases. Entomologist David Hughes at Pennsylvania State University in University Park and epidemiologist Marcel Salathé at Ecole polytechnique fédérale de Lausanne or EPFL, the Swiss Federal Institute of Technology in Lausanne, are leading the team creating the open-access database, known as PlantVillage.

Hughes, Salathé, and colleagues are developing PlantVillage as a tool for growers to take advantage of their smartphones to capture and share images of crop disease in their fields, as well as learn new techniques for battling those diseases. PlantVillage is aimed particularly at small subsistence farmers with limited resources for investing in new technology, but who can use their smartphones to get answers about diseased crops. The U.N.’s Food and Agricultural Organization estimates that plant diseases and pests reduce annual crop yields worldwide by 20 to 40 percent.

Collecting the images is a first step in developing PlantVillage’s utility for growers. A key feature of PlantVillage is machine learning algorithms that detect patterns in the collected images and data, and provide responses to queries. The system’s developers envision farmers using their smartphones to snap and upload a photo of a disease plant, which the PlantVillage database and algorithms would match, analyze, and return with guidance via the app, which is now available for iPhones.

Hughes and Salathé say PlantVillage is one of the largest free libraries on plant diseases, covering 154 crops and more than 1,800 diseases. “In addition to being a library, PlantVillage is a network of experts who help people around the world find solutions to their problems,” says Salathé in a joint statement. “Our goal is to let the smartphone do most of the diagnosis, so that human experts can focus on the unusual and difficult cases.”

The algorithms remains a bottleneck in PlantVillage’s development, due to the relatively small number of images collected so far to train algorithms to discriminate between diseased and healthy crops. But the developers plan to use the project’s open-source and open-access properties to solve that problem. “By providing all these images with open access, we are challenging the global community in two ways,” notes Hughes. “We are encouraging the crop-health community to share their images of diseased plants, and we are encouraging the machine learning community to help develop accurate algorithms.”

The developers plan to hold a crowdsourced online competition to create more algorithms that diagnose crop diseases. Hughes tells more about PlantVillage in the following video.

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Antibodies to Treat Staph Infections in Early Trial

MRSA bacteria

MRSA bacteria ( National Institute of Allergy and Infectious Diseases)

24 November 2015. A study testing the safety of antibodies to prevent and treat Staphylococcus aureus infections, including those contracted in hospitals, is underway in Vienna, Austria. The clinical trial is evaluating an experimental biologic drug for the prevention and treatment of S. aureus or staph infections made by Arsanis Biosciences, a biotechnology company in Vienna and Waltham, Massachusetts.

Many people carry S. aureus bacteria in their bodies with no ill effects, according to Centers for Disease Control and Prevention. But staph bacteria can cause serious infections, particularly in hospitals and clinics, such as sepsis in the blood stream, pneumonia in lungs, and endocarditis in heart valves. A CDC survey in 2011 shows about 1 in 25 hospital patients contracts an infection, resulting in 722,000 cases in acute care facilities, leading to about 75,000 deaths.

When staph bacteria become resistant to antibiotics, the danger becomes only worse. Methicillin-resistant Staphylococcus aureus or MRSA, for example, is resistant to many antibiotics, leaving physicians with few treatment options. In September 2014, the White House announced a national strategy to combat antibiotic resistant bacteria, responsible for 2 million illnesses and 23,000 deaths each year.

Arsanis Biosciences follows a different strategy, developing antibodies rather than antibiotics to address staph bacteria. The company designs monoclonal, or highly targeted, antibodies engineered to neutralize the virulence of bacteria infections, by generating an immune response to infections. These engineered antibodies, says Arsanis, work for longer periods in the body, thus can be given in smaller doses with fewer adverse effects.

The company’s lead product, code-named ASN100, is designed as a preventive medication for people at high risk for staph infections, as well as a treatment. ASN100 — developed with a partner company Adimab, in Lebanon, New Hampshire, a spin-off enterprise from Dartmouth University — is a combination of two monoclonal antibodies that neutralize six toxins created by the infections that cause cell and tissue damage, resulting from MRSA and the related methicillin-susceptible Staphylococcus aureus or MSSA.

The clinical trial is enrolling healthy volunteers to test ASN100 for safety, tolerability, and chemical effects in the body. Arsanis also has monoclonal antibodies in discovery and lead optimization for E. coli infections and pneumonia.

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Trial Tests Vibrating Mattress to Prevent Infant Apnea

Stochastic resonance mattress

Stochastic resonance mattress for preterm babies (Wyss Institute, Harvard University)

24 November 2015. A mattress that provides occasional mild vibrations was shown in a clinical trial to prevent episodes of interrupted breathing in preterm babies, a condition known as infant apnea. Results of the study testing the device, developed at the Wyss Institute, a biomedical engineering research center at Harvard University, were reported yesterday in the journal Pediatrics (paid subscription required).

Babies born prematurely often do not have a fully developed central nervous system that regulates and allows for non-stop breathing. As a result, some babies born before 35 weeks gestation experience periods when apnea occurs, causing their breathing to stop and heart rate to fall. Neonatal intensive care units need to constantly watch for these episodes, which can last up to 2 or 3 months before babies can breath constantly. Low doses of caffeine are given in some cases to keep preterm infants alert and breathing constant.

David Paydarfar, a neurologist on the faculty at Wyss Institute, and University of Massachusetts Medical School in Worcester, led the study testing a mattress for preterm babies designed to prevent apnea episodes. The danger posed by apnea, says Paydarfar in a Wyss Institute statement,”prompted us to develop a non-invasive, non-pharmacological solution that can address the immature respiratory control in these preterm infants.”

The mattress adopts stochastic resonance, a principle from physics where adding random noise to a signal in the right way and right time can improve the detection of that signal. Applied to biological systems, stochastic resonance should improve detection of neurological signals as well. Earlier research by James Collins, a Wyss Institute colleague, shows random vibrations act as noise in stochastic resonance to stimulate greater sensitivity in complex biological systems.

Payfardar, with colleagues at Wyss Institute and UMass medical school, developed a mattress for preterm babies that provides subtle vibrations acting as noise in stochastic resonance, to help regulate breathing and improve heart rates without waking the babies. Based on early pilot studies, the mattress provides vibrations only to the baby’s body to protect the head from adverse effects.

The team tested the device in a clinical trial with 36 preterm babies in the neonatal intensive care unit at Beth Israel Deaconess Medical Center in Boston, affiliated with Harvard Medical School. The babies had an average gestational age of 30.5 months and experienced at least one episode of apnea, low heart rate, or reduced blood oxygen levels. They received intervals of stochastic resonance stimulation for 30 minutes at randomly assigned periods, which were compared to randomly assigned periods of no stimulation. Researchers looked primarily for periods of apnea, low heart rate, and low blood oxygen levels.

The results show during periods when babies received stochastic resonance stimulation, the number of apnea events was reduced by half, compared to similar periods without stimulation. In addition, the number and intensity of low blood oxygen events were reduced by 20 to 35 percent during times of stimulation, and the intensity of low heart rate episodes was reduced by 20 percent.

Wyss Institute says it has patents on the technology, including the equipment, software and algorithms, which are available for licensing from the university.

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ARPA-E Funding 41 Energy Generation, Efficiency Projects

Ernest Moniz at 1776

Secretary of Energy Ernest Moniz speaking at 1776 (A. Kotok)

23 November 2015. Advanced Research Projects Agency-Energy, or ARPA-E, the agency funding riskier energy research and development initiatives in the U.S., announced funding for 41 new projects, including those at 19 private companies. The grants totaling $125 million were revealed today by Secretary of Energy Ernest Moniz at 1776, a technology incubator and seed fund in Washington, D.C.

Moniz underscored the key role of innovation in advancing technology to meet climate change goals in preparation for the U.N. conference on climate change, known as Conference of Parties or COP21 scheduled to begin 30 November in Paris. Innovation, says Moniz, will be a a major theme in Paris, since it’s a key driver in the adoption of technologies to mitigate the effects of climate change. “Innovation in this space,” noted Moniz, “keeps driving down costs of these technologies.”

ARPA-E funds research on advances in high-impact energy-related technologies deemed too early or risky for private sector funding. This latest group of grants were the result of an open-call for proposals, only the third such open call since 2009. Most ARPA-E funding rounds are related to specific agency priorities or themes. The competition for funding is highly competitive, with these 41 new projects representing only about 2 percent of all submissions. Moniz, who was a professor pf physics at MIT before becoming energy secretary, pointed out that “it is easier to get into MIT than to get an ARPA-E award.”

Of the 41 grants, 19 were awarded to private companies, with about the same number going to university researchers, and the remainder awarded to national labs and non-for-profit institutions. Of the private industry awards, a few went to major corporations including General Electric and Corning Inc., but most went to small, early-stage enterprises.

Among the recipients of 2015 ARPA-E grants is Marine BioEnergy Inc. in San Diego, a developer of acquaculture systems. In this project, Marine BioEnergy plans to create a cultivation system for algae biomass for biofuels in the open ocean that takes advantage of its water and sunlight, but can still submerge in times of storms or to avoid ships in the vicinity. With its $2.1 million award, the company plans to grow its crop in the  the U.S. Economic Exclusion Zone off California.

Another private sector grant recipient is Mackinac Technology Company in Grand Rapids, Michigan, a developer of window insulation systems designed to work with existing windows and frames in residential and commercial buildings. With its $2.5 million grant, Mackinac Technology is creating a transparent film that lets in more than 90 percent of sunlight, yet reflects ultraviolet and thermal-infrared energies to reduce heat loss in winter.

Proton Onsite, in Wallingford, Connecticut is receiving a $2.5 million award to develop a hydrogen-iron flow battery that plans to generate hydrogen for fuel cell vehicles, as well as store energy for the power grid. The device is expected to recharge either with electricity from the power grid or from exposure to sunlight. The company says its dual hydrogen generator and grid battery operates at a higher rate of efficiency than conventional electrolyzers that split water into hydrogen and oxygen.

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Chip Device Removes Nanoparticles from Plasma

Electrokinetic chip

Electrokinetic chip for isolating nanoparticles in blood (Univ of California, San Diego)

23 November 2015. A team from University of California in San Diego used a miniature electronic chip to quickly separate nanoparticles for delivering drugs from blood plasma. The process, with a technology developed in the engineering lab of Michael Heller at UC-San Diego and licensed to a spin-off company from the university, is described in a recent article appearing in the journal Small (paid subscription required).

Heller and colleagues are seeking an easier way to recover nanoparticles from blood for evaluation, which can help clinicians determine the effectiveness of drugs delivered with this method. Nanoscale particles — where 1 nanometer equals 1 billionth of a meter — are gaining more interest as a way to deliver therapies. Nanoparticles in various forms and chemistries flow through the blood and are delivered to and accumulate at the site of disease or injury, usually in smaller doses, and thus with fewer side effects.

Isolating therapeutic nanoparticles today, however, is a difficult and complex process, because of the particles’ tiny size and low concentration in blood. Today’s techniques, say the authors, generally require adding a concentrated sugar solution and separation with a centrifuge, or adding an agent that attaches to the particles, all of which can affect the particles and make them difficult to evaluate.

“We were interested in a fast and easy way to take these nanoparticles out of plasma,” says Heller in a university statement, “so we could find out what’s going on at their surfaces and redesign them to work more effectively in blood.”

Researchers — from the university’s engineering, medical, and neuroscience faculties — employed a technology developed earlier in Heller’s lab for separating the particles from plasma, the liquid part of blood. That technology adapts an electrokinetic process requiring a tiny sample of blood, 250 microliters, exposed to a lab-on-a-chip device creating an electric field. The oscillating field polarizes the particles of interest, pulling them out of the sample and collecting them on the chip’s electrodes.

The team reports the technique processed plasma samples with several types and materials of nanoparticles, including nanoscale lipsomes, tiny bubbles made with the same lipid membranes found in cells, and used more frequently for drug delivery. The technique, say the researchers, takes about seven minutes and requires no special sample preparation.

Once separated from the plasma, drug-delivery nanoparticles can them be inspected with an electron microscope for changes in surface or structure. The team says the technique can be used to test a patient’s blood in advance for reactions to nanoparticle drug delivery, as well as inspections after a nanoparticle drug is delivered.

The analytical chip used in this study was developed by Raj Krishnan, then a doctoral student in Heller’s lab, who started the company Biological Dynamics that licensed the technology from UC-San Diego. Biological Dynamics, founded in 2008 by Krishnan and others, applies the technology to diagnostics for a range of conditions including cancer, infectious disease, cardiovascular disease, and trauma.

The company’s lead product is a liquid biopsy for cancer designed to extract cell-free DNA and other biomarkers for tracking a cancer patient’s response to treatment, which quickly isolates and quantifies the biomarkers with a small sample of blood. The company says the product, known as TR(ACE) is being evaluated in clinical settings.

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FDA Approves Nasal Spray for Opioid Overdose

Narcan nasal spray

Narcan nasal spray (Adapt Pharma Ltd)

20 November 2015. The U.S. Food and Drug Administration this week approved the first formulation of a current drug to treat opioid overdose in nasal spray form. The Narcan nasal spray is made by Adapt Pharma Ltd., a company headquartered in Dublin, Ireland.

Opioids work by reducing the intensity of pain signals to the brain, particularly regions of the brain controlling emotion, which reduces effects of the pain stimulus. Examples of leading opioid prescription pain medications are hydrocodone, oxycodon, morphine, and codeine.

Abuse of opioid pain killers is described by Centers for Disease Control and Prevention as a growing epidemic, fueled in part by growing numbers of prescriptions written for pain killing drugs. CDC reports that in 2012, physicians in the U.S. wrote 259 million prescriptions for pain killers, enough for one bottle of pills for every adult in the country. As of July 2014, according to the CDC, 46 people die each day in the U.S. from an overdose of prescription pain killers. The 10 states with the highest rates of prescriptions for pain killers, says CDC, are in the South.

Narcan nasal spray contains the opioid overdose antidote naloxone, now administered by physicians or emergency medical technicians as an injection, but can also be given by family members or home health care givers. Naloxone activates and binds to opioid receptors in the brain to reverse the effects of natural and synthetic opioids, and is considered a standard treatment for an opioid overdose.

FDA says naloxone is already being used as an unapproved nasal spray by combining the drug with an atomizer. The agency says Narcan provides a consistent pre-measured dose of the drug, and can be used directly out of the box and administered by non-professionals, such as family members, as well as clinicians and first responders. Clinical trials of Narcan show a single dose delivered in one nostril provide as much or more naloxone as a conventional intramuscular injection, and works about as quickly.

Narcan received both fast-track and priority review from FDA, which provides for expedited review of new drugs that address unmet serious conditions, and offer improvements in safety or effectiveness over current drugs. FDA said it completed its review in less than four months.

Adapt Pharma says it arranged with the Clinton Health Matters Initiative to make the Narcan nasal spray available at a discounted price to group purchasers in law enforcement and first responders, public health, educational institutions, and community organizations.

In July 2015, as reported in Science & Enterprise, FDA designated another nalaxone nasal spray for priority review, made by Indivior, in Slough, U.K.

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Vital-Signs Sensors Built Into Ingestible Capsule

Ingestible vital signs device

Ingestible electronic device that measures heart and respiratory rates (Albert Swiston, MIT Lincoln Laboratory)

19 November 2015. Engineering and medical researchers developed and tested in pigs a swallowed capsule with sensors that records heart and respiratory rates in real time. The team from the bioengineering lab of Robert Langer and Lincoln Laboratory at Massachusetts Institute of Technology published its proof-of-concept results yesterday in the journal PLOS One.

The technology from the MIT team, with colleagues from Massachusetts General Hospital, is designed to address a need for measuring vital signs in burn or other trauma patients or in settings where regular health monitors are impractical, such as soldiers in combat. Vital signs sensors packed into a capsule could also improve health monitoring of people with chronic diseases and training of elite athletes.

Current technologies for monitoring vital signs require devices that come into contact with the skin, such as pulse oximeters or electrocardiograms, which can be difficult for burn patients. Wearable monitors are also available, but they can be uncomfortable or add weight and bulk, which would discourage their use by athletes. Plus, current ingestible devices are designed to monitor the digestive tract, not heart and breathing rates.

For this technology, the researchers adapted the principle of a stethoscope, a device that listens in on heart and respiratory rates. The team combined a tiny microphone with signal processing components that identify background noises in the digestive tract, then separate the resulting acoustic wave into heart beats or lungs inhaling and exhaling. For this study, the device is packed into a silicone capsule about the size of a multi-vitamin tablet and wired to an endoscope. A second microphone is placed over the heart.

The researchers tested the device with 6 anesthetized pigs, who were fed the capsule either when fasting or after taking food, both solid and liquid. “Through characterization of the acoustic wave, recorded from different parts of the GI tract,” says first author Giovanni Traverso in a university statement, “we found that we could measure both heart rate and respiratory rate with good accuracy.” Traverso is a gastroenterologist at Massachusetts General Hospital, and a researcher affiliated with MIT.

Among the limitations noted by the authors are differences in transit time through the gastrointestinal tract, with the best results noted in the upper tract — esophagus to the small intestine. Another issue was ambient noise, both internal and external, which the team believes can be addressed with more sophisticated signal processing algorithms. The researchers next want to develop the device further making a completely wireless system from FDA-approved materials.

Traverso and senior co-author Robert Langer founded the company Lyndra Inc. in Cambridge, Massachusetts to commercialize technology that extends the release of oral medications to one week. While the company is not working on ingestible diagnostics or vital signs monitoring, many aspects of its technology, including testing with pigs, are similar to the methods used in the study.

Senior co-author Albert Swiston and Traverso tell more about the device in the following video.

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Genomic, Patient Data Integrated for Precision Medicine

Doctor with tablet

(NEC Corporation of America with Creative Commons license)

18 November 2015. A collaboration of genomic profiling and software companies plans to integrate their services to provide what they call more informed precision medicine treatment options for cancer patients. Financial aspects of the agreement between genetic diagnostics enterprise Caris Life Sciences in Irving, Texas and software provider Syapse in Palo Alto, California were not disclosed.

Caris provides a service called molecular intelligence that analyzes the genomic composition of tumors from cancer patients, and compares the results with data from clinical studies to provide their doctors with treatment recommendations best fitting the patients’ tumor profiles. The company says it has more than 80,000 such tumor profiles in its databases.

The collaboration will be part of what Caris calls its centers of excellence, or COE, network for precision medicine. The network is made up of medical centers that provide precision medicine services and work to improve standards of care for molecular tumor profiling in oncology.

The agreement calls for participating medical centers in the Caris network to adopt Syapse software for integrating tumor profiles from Caris with data from electronic medical records. Syapse’s precision medicine platform includes a package tailored for oncology, including components for recording molecular profiles. The integrated records will also be made available, with identification removed, for sharing across the Caris network and aggregated to provide insights into clinical outcomes.

The combination of services, say the companies, will make it possible to better understand the nature of cancer in individual patients and identify effective treatments, as well as provide patients better access to new therapies and clinical trials. In addition, Syapse’s software is expected to help Caris network members participate in virtual tumor boards, where they can review cases and exchange guidance with network colleagues. Tumor boards bring together specialists across disciplines to review proposed treatments.

“Sharing the clinical and molecular profile of patients, alongside their treatments and outcomes,” says Jonathan Hirsch, president and founder of Syapse in a joint statement, “will enable members of the COE Network to collaboratively develop the best practices and clinical utility evidence needed to advance the practice of precision oncology.”

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Brain Tissue Banks Partner on Autism Research

Human brain

(, Flickr)

18 November 2015. Two repositories of brain tissue for research on neurological disorders agreed to coordinate their donation and distribution policies for studies of autism. The agreement aims to bring into alignment policies and practices of NeuroBioBank at National Institutes of Health and Autism BrainNet, a private tissue bank.

The deal covers brain tissue samples for research on autism spectrum disorder, a collection of neurodevelopmental conditions, marked by communication difficulties and impaired social interaction, as well as repetitive and stereotyped patterns of behavior. Some 1 in 68 children have autism spectrum disorder, according to Centers for Disease Control and Prevention, with males 5 times more likely to have the disorder than females. Classic autism is considered the most severe form of the syndrome.

Research on neurological conditions, including autism spectrum disorder, benefits from the availability of high-quality brain tissue. The NeuroBioBank, begun at NIH in 2013, collects post-mortem brain tissue in a network of academic research sites in the U.S. for studies of neurological and psychiatric disorders. Autism BrainNet also collects post-mortem brain tissue in a consortium of academic research sites, but focusing on autism spectrum disorder.

Under the agreement, National Institute of Mental Health, part of NIH, will bring together the two tissue banks to establish common best practices on donation and maintenance of brain tissue for research on autism spectrum disorder. The collaboration aims at writing standardized brain donation protocols that cover obtaining consent, ensuring privacy protection, processing, and maintaining donor tissue.

The common protocols are also expected to include procedures for collecting donors’ clinical, medical, and education records. In addition, the agreement plans to establish a catalog of available samples and data from both tissue repositories and enforce fair distribution rules for those samples.

NeuroBioBank is supported by National Institute of Mental Health, as well as  National Institute of Neurological Disorders and Stroke, and Eunice Kennedy Shriver National Institute of Child Health and Human Development, also at NIH. Autism BrainNet is supported by Autism Speaks and the Simons Foundation Autism Research Initiative.

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