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Test IDs Mesothelioma Years Before Symptoms Appear

Lungs illustration

(National Cancer Institute)

5 February 2016. A company spun-off from Purdue University designed a test that in a recent study detects cases of mesothelioma, a form of lung cancer, several years before symptoms develop. Results of the study conducted by MorNuCo Laboratories in West Lafayette, Indiana appear in the 22 January issue of the journal Clinical Proteomics.

Mesothelioma is an aggressive form of cancer affecting the lungs, but can also occur in the abdomen and heart cavities. In the lungs, which accounts for about three-quarters of the cases, cancer strikes the mesothelium, the protective layer of the chest cavity. Exposure to asbestos in the air increases the risk of contracting mesothelioma, which strikes 2,500 to 3,000 people in the U.S. each year, according to Mesothelioma Cancer Alliance.

MorNuCo Laboratories was founded in 2011 by former Purdue medicinal chemists and pharmacy school faculty D. James and Dorothy Morré, The company develops disease diagnostics that detect the Ecto-nicotinamide dinucleotide oxidase disulfide exchangers or Enox family of proteins found on the surface of cells, and released into blood and other fluids in the body. The Enox2 protein is associated with unregulated cell growth and expressed on malignant tumor cells, and according to the company takes on different forms that can identify 25 specific types of cancer.

The study reported on MorNuCo’s OncoBlot test to detect mesothelioma in individuals taking part in a cancer screening program among workers in Australia exposed to asbestos. OncoBlot tests for the presence of two Enox2 proteins with an antibody developed by MorNuCo. Both Enox2 proteins need to be present for a positive result.

The team from MorNuCo, led by James Morré, and University of Western Australia tested blood serum samples of 17 individuals participating in the cancer screening program going back as far as the 1990s who later developed mesothelioma. The results show the OncoBlot tests detected the presence of both Enox2 protein markers from 4 to 10 years — average of 6.2 years — before participants reported symptoms of the disease. In addition, one or both Enox2 proteins were missing in 14 of 15 patients with benign pleural plaques, non-cancerous scar tissue in the lungs resulting from asbestos exposure.

While the findings point to the utility of OncoBlot tests for early detection of mesothelioma, the authors say there is still a need for independent validation with a larger sample of participants in prospective studies, as well as retrospective studies like the one reported. MorNuCo says it’s preparing an application for clearance of the test by FDA as a medical device.

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FDA Assessing Opioid Regulatory Reviews, Labeling

Pills in blister packs

(PublicDomainPictures, Pixabay)

4 February 2016. U.S. Food and Drug Administration is evaluating its practices on reviewing applications for new opioid pain drugs and their labeling requirements, in light of the expanding epidemic of abuse and overdose.  An action plan with these steps was released today, although funding for new initiatives was not discussed.

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, fentanyl, and codeine. The illegal drug heroin is also an opioid derivative.

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 agency says more Americans now die every year from drug overdoses than they do in motor vehicle crashes.

FDA’s plan for revising its opioid regulations calls for reassessing its framework for evaluating risks and benefits of opioids, particularly when considering wider public health needs. FDA’s Science Board meets in March 2016, and is expected to take up this issue, and National Academy of Medicine is being consulted. The agency is also convening an expert committee to advise on new opioid drug applications that do not have properties or mechanisms to deter abuse.

In addition, the plan calls for new labeling requirements for opioids that act immediately, adding in more safety information and warnings. FDA already requires special warnings and safety labeling for extended-release and long-acting opioid formulations. Requirements for immediate-acting opioid drugs would resemble labels for the extended-release drugs. The agency will also convene its advisory committee on pediatric drugs to advise on a new framework for labeling opioids for children.

FDA notes it lacks evidence for evaluating long-term impacts of long-acting opioid formulations and will ask drug companies to provide that evidence in studies conducted after the agency approves marketing of new drugs in the U.S. The agency will also ask drug companies to increase their continuing education for health care providers on appropriate use of these products.

Another part of the plan calls for expanding access to formulations that discourage abuse and treatments for addiction and overdoses. In April 2015, FDA issued guidelines for conducting studies to evaluate opioid pain killers in abuse-deterrent formulations, but the agency now says it will move ahead with approval standards for generic forms of these formulations, which will have a high priority.

Likewise, FDA says it is reviewing options for making naloxone, a drug to treat opioid overdose, more accessible. In November, as reported in Science & Enterprise, the agency approved a nasal spray formulation of naloxone that can be administered by family members or home health caregivers, as well as medical professionals.

FDA’s plan does not give any new funding requirements, but it comes two days after the White House announced it is requesting an additional $1.1 billion in the fiscal year 2017 budget to expand access to treatment for prescription drug abuse and heroin use.

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Chip Designed for Efficient, Mobile Neural Networks

Neural network illustration

(geralt, Pixabay)

4 February 2016. An engineering lab at Massachusetts Institute of Technology designed a new processing chip that could allow running of neural networks on mobile devices. A team led by electrical engineering and computer science professor Vivienne Sze described and demonstrated the new chip on 2 February at the International Solid State Circuits Conference in San Francisco.

Sze and colleagues in MIT’s Energy-Efficient Multimedia Systems Group seek to develop more efficient, but still high-performance systems for multimedia applications that usually require a great good deal of computing resources.  In this case, Sze’s team is looking for alternatives to graphic processing unit or GPU chips now used to implement neural networks that simulate human thought, including the ability to recognize objects and people, or learn new skills.

While GPUs were designed initially to represent graphics on computing screens, they can be adapted to resource-intensive applications, such as neural networks. These applications of artificial intelligence are often called deep learning, but even high-power GPU chips still need to tap into data and power of remote systems in the cloud to perform deep-learning functions. More efficient circuits would make it possible to perform these functions completely on local devices, even mobile phones.

“Right now, the networks are pretty complex and are mostly run on high-power GPUs,” says Sze in a university statement. “You can imagine that if you can bring that functionality to your cell phone or embedded devices, you could still operate even if you don’t have a Wi-Fi connection. You might also want to process locally for privacy reasons.”

The team, including research scientist Joel Emer with NVidia (also on the MIT computer science faculty), a pioneering company with GPU chips, designed the new circuit — called  Eyeriss — with 168 cores, nearly as many as the 200 cores found in GPU chips, but with 10 times the power. The design separates the training of the neural network, where deep learning is implemented, from the trained network on the device. The implemented network in Eyeriss is also configured so cores that share data are adjacent in the circuit, removing the need to route data through the main memory.

In addition, tasks in Eyeriss are allocated to store both data describing the processing core’s function, as well as data needed for the task and manipulated by the core. These task allocations can be done dynamically on Eyeriss to maximize its efficiency. And to minimize the need for exchanges with remote data banks, Eyeriss’s cores directly store the data from the remote sources in a compressed format.

Sze and colleagues demonstrated an image-recognition task with Eyeriss at the conference. The designers believe the chip can be used to run algorithms for Internet of Things applications, where sensors built-in to vehicles, appliances, and other devices could exchange data with smaller local systems, thus requiring fewer exchanges with remote data banks. Neural networks in embedded systems could also provide more intelligence to autonomous robots.

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Ebola Monitoring System Devised with Genome Sequencing

Ebola genome sequencing lab

Ebola genome sequencing lab in Guinea (European Mobile Lab)

3 February 2016. An international team of scientists and engineers designed a mobile system using a hand-held genome sequencing device that provided real-time monitoring of the Ebola outbreak in West Africa in 2015. Researchers led by microbiologists Nicholas Loman and Joshua Quick at University of Birmingham in the U.K. published their findings in today’s (3 February) issue of the journal Nature.

The researchers from Loman’s group at Birmingham and elsewhere in Europe, Africa, Canada, and the U.S. were responding to the long delay in conclusively identifying Ebola viruses in patients during the height of the outbreak in West Africa in the spring of 2015. Sequencing viruses’ genomes can provide vital data to guide control efforts by health authorities, but sequencing required sending samples to remote labs, in some cases outside of Africa. The results of remote sequencing, which provide target signatures for therapies and identify mutations in the virus, were sometimes obsolete by the time they were reported to clinicians and health authorities.

To conduct the sequencing, researchers used the MinIon, made by Oxford Nanopore Technologies. MinIon is a disease surveillance system that analyzes DNA from blood samples, and operates as a plug-in peripheral on a laptop computer. Because MinIon is powered by the host laptop computer, it does not need an additional power source, unlike high-powered conventional DNA sequencing systems.

The MinIon technology is based on straining and isolating individual DNA strands through nanoscale pores in a membrane that allows for electronic sequencing processes to identify the base components of DNA passing through the pore. As reported in Science & Enterprise, astronauts aboard the International Space Station are testing the feasibility of portable DNA sequencing in space using the MinIon.

Loman, Quick, and colleagues built a mobile system built around the MinIon that could be transported easily and deployed in field sites. The entire system, including the laptop computer hosting the MinIon fits into an ordinary suitcase and weighs less than 50 kilograms (110 pounds), the weight limit for airline luggage.

The Birmingham team worked with European Mobile Laboratory Project and World Health Organization to test the system on the ground in Guinea from March to October 2015. During that time, researchers sequenced 142 samples from patients, with the sequencing itself taking no more than 60 minutes, and providing analytical results in less than 24 hours.

“Having a portable DNA sequencing system opens up the possibility to do outbreak genome sequencing in real-time,” says Loman in a university statement, “which can directly impact on the response on the ground, as well as providing a wealth of information about pathogen evolution. Crucially we shared our data as it was generated, increasing its use immensely.”

While WHO declared the outbreak officially over in January 2016, isolated cases of Ebola continue to be reported. The research team left the sequencing system in Guinea for health authorities to continue their surveillance of the disease.

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Genome-Editing Company Raises $94 Million in IPO

NASDAQ display

(bfishadow, WikimediaCommons)

3 February 2016. Editas Medicine, developer of treatments for disease that harness editing of the human genome, is raising $94.4 million in its initial public stock offering. The company, trading on the Nasdaq exchange under the symbol EDIT, issued 5.9 million shares priced at $16.00. As of 12 noon on 3 February, the stock is trading at $17.00 a share, up 6.25 percent, while the Nasdaq overall is down 0.8 percent.

Founded in 2013, Editas Medicine is designing therapies with the ability to turn off and on and repair genes causing disease. The company’s technology uses a technique called clustered, regularly interspaced short palindromic repeats, or Crispr, and related Crispr-associated protein 9, together known as CRISPR-Cas9. With CRISPR-Cas9, the Cas9 protein binds to targeted RNA molecules generated by the human genome. The RNA molecules then guide Cas9 proteins to specific genes needing repair, making it possible to address root causes of many diseases.

In December 2014, the Cambridge, Massachusetts company licensed the work of its founders George Church and David Liu of Harvard University and Feng Zhang of the Broad Institute, a medical research center at Harvard and MIT. Church, Liu, and Zhang are pioneers in the development of Crispr-Cas9 and serve as scientific advisers to Editas. Since September 2015, as reported in Science & Enterprise, Zhang published studies demonstrating methods to simplify the Crispr technique and improving its accuracy.

Researchers from Editas in March 2015 demonstrated repair of genetic defects causing sickle-cell disease, an inherited blood disorder affecting hemoglobin that delivers oxygen to cells in the body. The team applied Crispr/Cas9 to a process known as gene conversion, where the mutated gene is repaired with a different, but closely related gene.  That demonstration used lab cultures and was not tested in humans or lab animals.

An international summit on genome editing in December 2015 established voluntary guidelines for further research and development of Crispr and related techniques. Those guidelines allow continued work with editing of genes in somatic cells, where the genomes are not transmitted to future generations. Examples include editing genes for sickle-cell disease or improving the ability of immune cells to target cancer. The guidelines, however, ask that clinical applications to germ line cells — for example, in human embryos — not proceed until much more is known about their medical and social consequences.

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Many FDA Advisory Speakers Found with Industry Funding

Meeting microphone

(Fill, Pixabay)

2 February 2016. A review of an FDA advisory committee on cancer drugs finds nearly one-third of speakers at its meetings receive financial support from companies making the drugs under review. The analysis by Vinay Prasad at Oregon Health and Science University and Matthew Abola, a medical student at Case Western Reserve University, is reported in yesterday’s (1 February) issue of the journal JAMA Internal Medicine (paid subscription required).

Prasad is a  a hematologist-oncologist at OHSU, as well as a scholar at the school’s Center for Health Care Ethics. He and Abola examined transcripts of 28 meetings of the Food and Drug Administration’s Oncologic Drugs Advisory Committee that reviews and evaluates data on drug products for treating cancer, from 2009 to 2014. The study excluded 21 meetings during that time without public hearings, or where cancer drugs were not discussed.

FDA’s advisory committees seek independent outside guidance on new therapies and medical devices. The Oncologic Drugs Advisory Committee has 13 members mainly with a background in cancer care as well as biostatistics. One consumer representative is also authorized among the voting members, in addition to a non-voting industry representative. As with other advisory committees, its recommendations are not binding, but often predict the FDA’s decision.

Prasad and Abola identified 103 speakers at the 28 committee hearings. Of those speakers, 3 in 10 (30%) had some financial connection with the companies making the drugs being reviewed, either from funding of travel to attend the meeting or as representatives of organizations supported by the companies. Two of the speakers revealed their organizational affiliations, but not the financial support received by the companies making the drugs, which the research team discovered later on.

Among all 103 speakers, nearly half (45%) experienced the type of cancer which the drug under review addresses, while about 3 in 10 (31%) actually used the drug being reviewed. In addition, 2 speakers were principal investigators of key clinical trials testing the drugs being discussed. The researchers examined comments made by speakers in the meeting transcripts, and nearly all speakers (92%) spoke favorably about the drugs in question. Only 6 of the 103 speakers did not support FDA approval of the drugs, with none having a financial connection to the drug’s developer.

Because such a large percentage of the speakers are cancer patients, say the authors, they can offer unique perspectives and deserve to be heard. “Some of the stories are really compelling,” notes Prasad in a university statement, “but it’s a mistake to assume that people who speak at these hearings represent the average patient or express what the average patient wants.” Prasad adds, “Patients who suffered real side effects, they are not the ones able to travel to these meetings.”

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Workplace Heart Health Platform in Development

Measuring blood pressure

(Wikimedia Commons)

1 February 2016. American Heart Association is developing a technology platform to help people at work track progress toward their wellness goals, and allow companies to evaluate their corporate wellness programs. The platform takes advantage of cloud computing power from the IBM Watson system and connects users through the Web or mobile access.

The new system is based on American Heart Association’s assessments for individuals to measure factors affecting heart health, for improving overall wellness and reducing the incidence of heart disease. Centers for Disease Control and Prevention says heart disease is the leading cause of death for both men and women, resulting in 610,000 deaths each year, or about 1 death in every 4. Coronary heart disease is the most common heart disorder, causing some 370,000 deaths. In addition, 735,000 Americans have a heart attack each year, including 525,000 individuals who have  heart attacks for the first time.

The platform gathers data with the association’s Life’s Simple 7 questionnaire that measures an individual’s performance on seven cardiovascular indicators — smoking, maintaining a healthy weight, exercise, healthy food choices, managing blood pressure, controlling cholesterol, and reducing blood sugar — which can help reduce risk for heart disease, stroke, and cancer. These indicators are then collected with their employers’ scores on best practices to compute an overall workplace health achievement index, providing a measure of a company’s workplace health culture.

American Heart Association contracted with health technology company Welltok to collect and initially process individual wellness and company health-culture data. Welltok offers its CaféWell health optimization platform for employees to connect and engage with their wellness information, while maintaining legal-mandated privacy controls. In the new system, Welltok is providing data-collection routines both for Web and mobile access, as well as importing data from devices such as fitness trackers, blood-pressure cuffs, and wireless scales.

In addition to assessments for individuals and employers, the system is making use of IBM Watson, a cloud-based analytical platform that analyzes large volumes of data and can respond to queries made in natural language. In the American Heart Association program, Watson is expected to provide insights and guidance for companies to better support their workers’ health goals and optimize overall workforce health. For health applications, Watson’s data records are de-identified and processed to provide evidenced-based answers. The system’s deep learning capabilities will make it possible to train Watson in evidence-based heart health issues, goals, and measures.

American Heart Association says a study it commissioned finds employees respond and feel encouraged by senior management when workplace health programs are available. The results show staff taking part in workplace health programs are more than twice as likely to eat healthy, and encourage greater job satisfaction.

Disclosure: The author owns shares in IBM.

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Illumina Providing Genomic Analysis for Precision Medicine

Genetic testing illustration

(National Institute of General Medical Sciences, NIH)

1 February 2016. Illumina Inc., a developer of genetic systems, is analyzing genomic data at four medical centers to integrate with patients’ electric health records for precision medicine. The San Diego company’s analytical services are expected to sequence and characterize the genomes of more than 200,000 individuals in the U.S. and Canada.

Medical centers taking part in the initiative are Vanderbilt University in Nashville, University of Colorado in Denver, Partners HealthCare in Boston, and Montreal Heart Institute in Quebec, Canada. Vanderbilt is providing 100,000 patients for the project, with the other medical centers offering between 25,000 and 50,000 participants.

The medical centers plan to use the data to discover underlying genetic factors contributing to heart disease, cancer, Alzheimer’s disease, bipolar disorder, and Crohn’s disease, among others. Each facility has a biobank, where specimen samples are collected and will be analyzed by Illumina. Each medical center also uses electronic records for storing patients’ clinical data as well as the genomic analyses.

Illumina will conduct its analysis with genotyping systems that the company says identify mutations and variations quickly. The company also expects to offer methylation sequencing, useful for identifying epigenetic factors, those outside the genome that influence gene expression.

Vanderbilt University, providing about half of the samples, will add the Illumina analyses to its BioVu collection of de-identified blood samples offered by patients with their consent. The university says it has some 150 research studies underway making use of BioVu. Nancy Cox, director of Vanderbilt’s Genetic Institute, says in an Illumina statement that BioVu “is at the core of a vision that will combine genome variation, biomarker data, patient electronic medical record information and pharmacogenomic data to advance personalized medicine.”

Montreal Heart Institute, offering about a quarter of the samples, will use Illumina’s multi-ethnic genotyping services to identify genetic predictors of responses to drugs for treating cardiac and metabolic disorders. A part of those samples, says the institute, will also be included in a study following a group of patients over time who took part in an earlier clinical trial.

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Allergan, AstraZeneca Partner on Drug-Resistant Bacteria

Bacteria growing in petri dishes

(Centers for Disease Control and Prevention)

29 January 2016. Pharmaceutical companies Allergan and AstraZeneca are developing a new treatment for infections caused by a type of bacteria already resistant to antibiotics. Financial aspects of the collaboration between the enterprises were not disclosed.

The agreement calls for the two companies to develop and commercialize ATM-AVI, a new drug that treats infections from metallo beta-lactamase or MBL producing gram-negative bacteria. These bacteria, a subset of carbapenem-resistant enterobacteriaceae, are considered particularly difficult to treat with current antibiotics, and infections from these pathogens are often found among people with weakened immune systems in health care facilities.

ATM-AVI combines the antibiotics aztreonam and avibactam. Aztreonam kills bacteria causing several types of infections, including pneumonia, urinary tract, gynecological, skin, bone, joint, stomach, and blood infections. Avibactam, marketed as Avycaz by Allergan, is prescribed for complicated intra-abdominal infections, as well as infections of the urinary tract.

Allergan notes that aztreonam has limited utility by itself against MBL-producing gram-negative pathogens because of enzymes produced by the bacteria that deactivate the drug. With avibactam added, however, aztreonam’s ability to fight these pathogens is restored. AstraZeneca says ATM-AVI is currently in early-stage clinical trials. “Gram” refers to a classification for bacteria where the microbes either retain (gram-positive) or shed (gram-negative) a test stain on their protective cell coatings.

The collaboration, says Allergan, builds on a partnership between AstraZeneca and Biomedical Advanced Research and Development Authority, or Barda, a division of the U.S. Department of Health and Human Services, begun in September 2015. Under that agreement, Barda is supporting development of ATM-AVI for gram-negative infections for which few treatments are new available, and can be used deployed in case of attack by biological agents, including meliodosis, glanders, and plague.

Under the agreement, Allergan gains the drug’s commercialization rights for the U.S. and Canada, while AstraZeneca secures rights to commercialize ATM-AVI elsewhere. Allergan, headquartered in Dublin, Ireland, is being acquired by the U.S. pharmaceutical company Pfizer for an estimated $160 billion, with that transaction scheduled to close in the second half of 2016.

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FDA Approves Nasal Spray Migraine Therapy

Headache graphic

(geralt, Pixabay)

29 January 2016. The Food and Drug Administration approved a treatment for migraine headaches delivered as a powder sprayed into the nose. The therapy, marketed as Onzetra by Avanir Pharmaceuticals, is a formulation of sumatriptan, an approved oral drug for treating migraine symptoms.

Migraine is a neurological syndrome causing severe headaches along with nausea, vomiting, and extreme sensitivity to light and sound. In some cases, migraines are preceded by warning episodes called aura including flashes of light, blind spots, or tingling in arms and legs. Migraine Foundation says the syndrome is one of the top 20 disabling disorders and estimates some 36 million people suffer migraines in the U.S., including 14 million who experience migraines nearly every day or more often.

Sumatriptan, approved by FDA in 1992, stimulates serotonin receptors in the brain that narrow blood vessels and stop pain signals sent to the brain. Serotonin is a neurotransmitter chemical generated in the brain, regulating signals between neurons that helps maintain mood balance. Decreased levels of serotonin are associated with depression.

Onzetra is administered with a nasal delivery system, where sumatriptan is absorbed faster into the brain than pills, which must be absorbed from the stomach. The delivery device, which the company calls Xsail, carries a low, measured dose of the medication in dry powder form, with a piece that fits in the patient’s nostril and a separate piece that goes in the mouth. The patient exhales into the device, which sends the dose of sumatriptan into the nose and into the nasal passages, deeper than can be delivered with a normal nasal spray, for transfer into the blood stream near the brain.

Avanir conducted a number of clinical trials, including intermediate and late-stage studies with more than 300 participants. The results, say the company, show more individuals with migraines taking Onzetra report headache relief within 30 minutes, and at other points up to 2 hours after taking the drug, than participants receiving a placebo. The trials also report a low incidence of adverse effects from the treatment.

Approval by FDA, however, was delayed three months due to questions from the agency about errors in using the Xsail device, which required Avanir to conduct an additional human factors study to address those concerns. FDA’s approval covers treatment for migraines after they occur, either with or with aura, and not for prevention of migraines. In addition, the drug is approved only after a clear diagnosis of migraine is made. Approval does not cover use of the drug for cluster headaches, a cyclical attack of severe headache pain.

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