The U.S. Food and Drug Administration yesterday cleared for marketing high-throughput sequencing systems by Illumina Inc. in San Diego to analyze a person’s DNA. In a commentary on this approval in New England Journal of Medicine, FDA director Margaret Hamburg and National Institutes of Health director Francis Collins say, “Access to these data opens the door for the transformation of research, clinical care, and patient engagement.”
Sequencing an individual’s DNA reveals the precise order of the base parts in a DNA strand, known by their initials A, G, C, and T. Advanced and powerful computing makes it possible to determine this sequence order for the entire genome, revealing information about a person’s genetics, such as mutations that contribute to various cancers. DNA sequencing technology has advanced to the point that entire genomes can be sequenced in 24 hours and under $5,000, a process that once took months and cost millions of dollars.
FDA cleared Illumina’s MiSeqDx instrument platform and related reagent kits that will allow medical labs to develop tests based on sequencing data. The MiSeqDx system analyzes the genes isolated and copied from blood samples, then compares the individual’s genomic sequence to a reference or model sequence, highlighting any differences. FDA granted Illumina’s application in a de novo petition, a regulatory procedure where equivalent devices are not yet on the market, and the applicant needs to show evidence of the device’s effectiveness.
FDA also cleared two of Illumina’s MiSeqDx systems customized for sequencing genes associated with cystic fibrosis, an inherited disease resulting in build-ups of damaging mucus in the lungs, airways, digestive, and reproductive organs. Illumina’s systems check for variations in the CFTR gene, where mutations are associated with the disease, and sequences the gene to detect differences with a reference CFTR gene. FDA says Illumnia validated its systems against standards developed through FDA’s partnership with National Institutes of Standards and Technology.
Hamburg and Collins, in their New England Journal of Medicine article, say new sequencing technology can advance pharmacogenomics, the application of genomic data to find the right drug and doses for individual patients. The authors say clinical use of pharmacogenomics has been limited because of the difficulty in getting genomic data into the hands of physicians when prescribing therapies. Having genomic data available in or linked to a person’s medical records would make it easier to prescribe more individualized treatments, and remove the need for first taking DNA specimens, shipping them off to a lab, and waiting for the results.
The authors highlight, however, areas that still need to be advanced before personalized medicine is more the rule than the exception. “We need to continue to uncover variants within the genome,” say Hamburg and Collins, “that can be used to predict disease onset, affect progression, and modulate drug response.” The authors also indicate new genomic findings need validation, reimbursement issues need to be addressed, and new regulatory policies are needed to protect patients’ rights in questions involving the use of genomic data in disability, life, and long-term care insurance.
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A therapy using genes to induce production of an enzyme for heart cells to restore their use of calcium was found to help heart failure patients in a clinical trial reduce their incidents of cardiac problems over a three-year period. Researchers at Mount Sinai Health System in New York, with colleagues from the biotechnology company Celladon Corp. in San Diego, University of California in San Diego, and University of Pennsylvania reported their results today at a meeting of American Heart Association in Dallas.
The paper discusses findings from a clinical trial of a candidate gene therapy with 39 congestive heart failure patients. Heart failure occurs when heart muscles cannot pump enough blood, which can result from narrowed arteries or the long-term effects of high blood pressure.
Research by Roger Hajjar, director of Mount Sinai’s cardiovascular research center and others, led to an approach for treating heart failure that introduces healthy SERCA2a genes into the coronary arteries of patients to help heart cells restore their proper use of calcium. The therapy involves SERCA2a genes that produce SERCA2a enzymes, which help drive the pumping action of the heart, and are often deficient in heart failure patients. Without sufficient SERCA2a enzymes, calcium stays longer in heart cells than needed, and encourages overgrowth of the number and size of heart cells, leading to an enlarged heart in heart failure patients.
The clinical trial, known as Calcium Up-Regulation by Percutaneous Administration of Gene Therapy In Cardiac Disease or CUPID 1, first tested the therapy for safety, and then compared the treatments to a placebo. The trial was conducted by Celladon that is commercializing the therapy. Hajjar is a scientific co-founder of the company and serves on its advisory board.
The first phase of the trial tested the therapy, called Mydicar by the company, at several dosage levels, which were found to be safe and well-tolerated by heart failure patients. After 12 months, the group receiving a high-dose of Mydicar had fewer heart problems and deaths from any cause than the group receving the placebo.
After three years, recurrence of heart problems was reduced by 82 percent among patients receiving the therapy. Also after three years, 13 deaths occurred among the patients in the trial, 6 of which among those who received the placebo, 3 each in the low- and mid-dose patients, and 1 in the high-dose patients. Celladon says no safety concerns were reported in the three-year period.
The company is recruiting participants for an intermediate stage clinical trial testing Mydicar against a placebo among heart failure patients. That trial aims to enroll 250 patients in 63 locations.
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A study in Philadelphia shows consumers who read nutritional labels on restaurant menus purchase items lower in calories, sodium, and saturated fats than patrons of that restaurant chain overall. The results of the study by researchers at Drexel University, University of Pennsylvania, and Philadelphia’s public health department appear online in yesterday’s advance issue of the American Journal of Preventive Medicine (paid subscription required).
Nutritional labels in restaurants are becoming required in more locations nationwide. In Philadelphia, full-service chain restaurants with more than 15 locations are required to post calorie, sodium, fat, and carbohydrate information for each item on their menus. Fast-food restaurants in Philadelphia must give calorie information on menu boards and other nutritional data on request. The national Patient Protection and Affordable Care Act will, when fully implemented, require nutritional information at the point of purchase for all fast-food and full-service chain restaurants with more than 20 locations.
The researchers collected 648 customer surveys and payment receipts in 2011 at seven locations of a full-service restaurant chain. Two of the locations had nutritional information on their menus, while the other five locations did not.
The overall results indicate these restaurants are not the best place to go for sound nutrition. On average, customers ate meals with 1,800 calories, of which 1,600 calories came from the food and the remainder from beverages. For most people, about 2,000 calories a day — from all meals – is recommended. Their selections also far exceeded recommended daily limits for sodium (2,300 milligrams) and saturated fat (20 grams).
The presence of nutritional information on the menus, however, suggests the labels at these locations are having an influence on consumers. About 8 in 10 customers at locations with nutritional labels said they saw the labels, and about a quarter (26%) said they used the labels when ordering.
Where the menus had nutritional information, consumers overall bought items with 155 fewer calories, counting both food and beverages, 224 milligrams less sodium, and 3.7 fewer grams of saturated fat, compared to customers at outlets without nutritional labels. Among those who read the nutritional labels – 26 percent — the results indicate an even greater impact: nutritional label readers bought items with on average of 400 fewer calories, 370 milligrams less sodium, and 10 fewer grams of saturated fat.
“This is the first field-based study of mandatory menu labeling laws,” says Drexel’s public health professor and lead author Amy Auchincloss in a university statement, “that found a large overall adjusted difference in calories between customers who dined at labeled restaurants when compared to unlabeled restaurants — about 155 fewer calories purchased.”
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David Kisailus, left, and lead author Jianxin Zhu (UC-Riverside)
Engineers at University of California in Riverside discovered a process for improving cathodes in lithium-ion batteries found in today’s electric cars and most electronic devices, and thus their performance. The team from the lab of Riverside’s David Kisailus published their findings in this month’s issue of the journal Crystal Growth and Design (paid subscription required).
The researchers aimed to improve the efficiency of a key component of lithium-ion batteries, the cathode. In lithium-ion batteries, electrons flow from one electrode, known as the anode, to another electrode, the cathode, through an electrolyte. The materials chosen for these components determine the battery’s power and capacity.
Many of today’s lithium-ion batteries use a cathode made of lithium iron phosphate, a material that provides thermal and chemical stability, low toxicity, and low cost. But lithium iron phosphate also does not do a good job in conducting electric power, nor are lithium ions very mobile in this material.
Kisailus and colleagues, including former lab members now at Berkeley and Brookhaven National Labs, devised a process to alter the size and shape of the nanoscale particles in the lithium iron phosphate, making the particles more uniform and get those particles to move faster in a battery cathode. Their process involves heating the material under pressure, in a medium of solvents.
The process resulted in more evenly-sized primary crystalline lithium iron phosphate nanoparticles inside larger secondary particles. The researchers say this composition reduces the path for lithium ions to travel, while maintaining a high density. Lab tests show cathodes made with this new configuration had a larger discharge capacity at higher rates than comparable cathodes made with single-crystal particles.
Kisailus’s team was also able to trace battery performance back to the type of nanoscale structure in the lithium iron phosphate, and the synthesizing process for that structure. The researchers are refining the process to further improve battery performance, and make it more scalable, thus more economically feasible.
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A system developed by a University of Minnesota medical student helps rehabilitating stroke patients gain more use of their hands and arms by visualizing their thoughts through virtual reality. Alexander Doud, who developed the system while a masters degree student in the lab of Minnesota biomedical engineering professor Bin He, is scheduled to report his findings today at a meeting of American Heart Association in Dallas.
Among the techniques for stroke patients in rehab is to have a therapist physically move the patient’s hand and arm, while asking the patient to imagine making that movement. That practice technique helps reactivate regions in the patient’s brain for making those movements.
Doud’s system captures the patient’s brain activity through an electroencephalogram (EEG) that measures electrical activity in the brain. The patient is then asked to visualize moving a hand or arm in a certain way, or to perform a simple task. The patient’s thoughts of hand or arm movement are then translated into virtual reality images displayed on anaglyphic (3-D) glasses, giving the illusion of the patients making those movements.
With lab colleagues at Minnesota, Doud tested the system with six stroke patients still experiencing weakness in one side of their bodies. The results show patients using the virtual reality system can achieve accuracies up to 81 percent in performing tasks like picking up a glass of tea or water.
Moreover, the patients can get these results in as few as three sessions, each two hours in length. Tests with controlling movements of a computer cursor that served as a control, show similar (87%) achievement levels.
Doud recognizes the study may prove the concept, but the system still needs more testing on larger samples and a greater variety of tasks. The team’s paper notes that stroke management in the U.S. is estimated to cost nearly $74 billion in 2010, and a system of this kind can reduce the amount of time a therapist needs to devote to a single patient, making rehab a more affordable experience for stroke patients.
In addition to studying medicine, Doud is founder (with Natalie Doud) of Synaptic Design, a Minneapolis human-factors design firm. The company, however, is not developing the virtual reality system tested in the study.
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(National Institutes of Health)
A new challenge on InnoCentive is seeking a technique for storing and growing endothelial progenitor cells captured from blood samples and vital for research on and testing for various disorders. The competition has a purse of $25,000 and a deadline of 5 January 2014 for submissions.
InnoCentive in Waltham, Massachusetts conducts open-innovation, crowd-sourcing competitions for corporate and organization sponsors, in this case the Cleveland Clinic. InnoCentive calls this kind of competition a “theoretical challenge” that requires the entrant to propose implementation of an idea, but one that need not yet be a proven concept.
Endothelial progenitor cells are precursor cells made in bone marrow that circulate through the bloodstream and can develop into blood vessel tissue. Impaired development or functioning of endothelial cells contributes to a number of diseases, including pulmonary arterial hypertension, atherosclerosis, diabetes, and Alzheimer’s disease.
The sponsor, Cleveland Clinic, is particularly interested in finding better ways of storing and growing endothelial progenitor cells, which when taken from blood or tissue samples today, must today be plated and processed within two hours. This tight time constraint severely restricts the number of patients available to provide these cells for research and testing.
Cleveland Clinic is looking for solutions that can extend the shelf life of endothelial progenitor cells in blood, so samples can be shipped overnight for processing the next day. The clinic plans to apply the solution to its research on pulmonary arterial hypertension, a chronic and incurable disease that abnormally constricts arteries that carry blood to the lungs, leading to increased blood pressure and extra strain on the heart.
Contestants need to prepare a written proposal for this challenge that can be an early stage idea — before the concept is proven — but still able to be implemented. In a theoretical challenge, says InnoCentive, the sponsor is looking for detailed descriptions and specifications that bring the idea closer to an actual product or service.
To receive an award in this challenge, winning contestants will be required to transfer to Cleveland Clinic exclusive intellectual property rights to their solutions. For winning participants who cannot transfer exclusive intellectual property rights, the sponsor will consider partial awards.
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Catabasis Pharmaceuticals Inc., a clinical-stage biotechnology company in Cambridge, Massachusetts, completed its second venture funding round, securing $32.4 million. The round was led by new investor Lightstone Ventures, with participation by the company’s current investors: SV Life Sciences, Clarus Ventures, MedImmune Ventures, and Advanced Technology Ventures.
Catabasis Pharmaceuticals develops medications to treat cardiovascular, metabolic and inflammatory diseases, with a technology based on the research of Steven Shoelson of Harvard Medical School and Joslin Diabetes Center. Shoelson, a co-founder of the company in 2008, conducts research on the key role of inflammation linking obesity to insulin resistance, type 2 diabetes, and cardiovascular disease.
The platform at Catabasis to develop its therapies is called Safely Metabolized And Rationally Targeted or SMART linker technology that targets multiple points along particular disease pathways. Linkers, says the company, are small sub-molecular components that connect therapeutic molecules, but remain inactive in the bloodstream until they reach the target cells at various points along the pathway.
Once at their targets, the drug molecules are broken off into their active components where they can have an immediate therapeutic impact. The company says this technology makes it possible to produce drugs that address their targets more precisely, with greater safety and fewer adverse effects.
Catabasis has two candidate compounds in clinical trials. Its lead candidate, CAT-2003 that addresses a pathway synthesizing fatty acids is in intermediate-stage trials as a treatment for hypertriglyceridemia, a condition where triglyceride levels become elevated as a result of diabetes or obesity. Another trial is testing the compound in combination with statins to treat high levels of cholesterol in the blood.
Another compound, CAT-1004, completed early stage trials as a treatment for inflammatory bowel disease. CAT-1004 targets a key pathway that responds to signals triggering inflammation in the gastrointestinal tract. The company expects to use the proceeds from the funding round to continue these trials as well as advance compounds still in the preclinical
The lead investor in the financing is Lightstone Ventures, a venture capital company in Palo Alto, California that specializes in life sciences enterprises, mainly early-stage companies.
Hat tip: Fortune/Term Sheet
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Prototype wireless power transfer device (Richard Ebersohl, North Carolina State University)
Engineers at North Carolina State University in Raleigh developed a new, more dynamic, approach for wirelessly charging moving electric vehicles and built a small-scale prototype to prove the concept. The team led by electrical engineering professor Srdjan Lukic published its findings online in a recent issue of the journal IEEE Transactions on Power Electronics (paid subscription required).
The technique created by Lukic and colleagues improves the efficiency of transferring power from a stationary source — the charging station — and a vehicle in motion. A type of earlier charging system for moving vehicles requires large transmitter coils that emit a low-level electromagnetic field to provide a sufficient quantity of power for the vehicle. But the field created by the large coil is imprecise, with power transferring to the vehicle frame as well as the motor. That large blanketing field is not only inefficient, but also raises safety concerns.
Another earlier approach tried to address these concerns with a collection of smaller transmitter coils. The large number of coils required, however, adds cost and complexity to the solution, and also calls for more precise targeting and detection technology to make it possible to transfer the power needed to charge the vehicle.
The solution devised by Lukic and colleagues in NC State’s Advanced Transportation Energy Center tries to take the best of both approaches. The system has transmitter and receiver coils of about equal size, which helps make the transfer of power more efficient. As with earlier technologies, the power transmitter coil is stationary, while the receiving coil is installed in the vehicle.
The NC State researchers, however, built a capability into the coils to couple electronically with each other when the receiver comes into range of the transmitter. When within range of the receiver, the transmitter coil is designed to increase its power output by 400 percent. The transmitter coil then returns to it original output when the vehicle and its receiving coil leave the transmitter’s range.
Lukic and colleagues built a small-scale prototype, which while functional, only transfers a small quantity of power — 0.5 kilowatts. The team is working on a more powerful 50 kilowatt system, which they say would also be more practical.
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Lymphocyte (National Cancer Institute)
The company immatics biotechnologies GmbH in Tuebingen, Germany and the global pharmaceutical maker Roche will collaborate on discovery and development of cancer vaccines and therapies that harness the human immune system. The deal will provide immatics (spelled in all lower case) an immediate payment of $17 million, but future payments to the company could reach as high as $1 billion.
The immatics technology uses mass spectrometry, genomics, biochemistry, and immunology to identify tumor-associated peptides derived from human cancer tissue that are characteristic of a specific type of cancer — e.g., breast or colon cancer — yet still sufficiently common to be shared by as many patients as possible. These tumor-associated peptides also seek to be linked to proteins considered key to survival of tumors, but should also provoke a strong immune response by patients.
In addition, the company says it can use these tumor-associated peptides to generate vaccine candidates in a shorter period of time than other current methods, usually within 24 months. These same peptides can also serve as the basis for antibodies and T-cell receptors — molecules on the surface of lymphocyte or white blood cells in the immune system that attract antibodies — for the development of immunotherapies.
While immatics has products to treat colon and treat kidney cancer in intermediate- or late-stage clinical trials, the collaboration with Roche focuses on therapies much earlier in the development cycle. The most advanced of these products is code-named IMA942 to treat gastric cancer, which expected to begin early-stage trials. Under the deal, Roche will take over further clinical development and commercialization of IMA942.
The deal also calls for immatics to identify candidates based on tumor-associated peptides to treat prostate and non-small cell lung cancer. As with IMA942, Roche will be responsible for clinical development and commercialization of any additional therapies from the collaboration.
Under the deal, Roche will make an initial payment to immatics of $17 million. Future milestone payments and sales royalties across the three types of cancer therapies could reach as high as $1 billion, according to a statement issued by the companies.
Hat tip: FirstWord Pharma
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(Agricultural Research Service/USDA)
Researchers at University of California in Los Angeles found feeding a bio-engineered tomato to lab animals cuts their production of a fatty acid believed to contribute to high cholesterol levels. The team led by Alan Fogelman, director of the atherosclerosis research unit at UCLA’s medical school published their findings in the December issue of the Journal of Lipid Research (paid subscription required).
Fogelman, with co-authors Mohamad Navab and Srinivasa Reddy, are principals in the biotechnology company Bruin Pharma that licensed the technology developed in this research from UCLA, which owns the patents.
Fogelman’s team, which includes colleagues from University of Alabama–Birmingham and University of Kentucky, investigated the role of a lipid — fat or oil — known as unsaturated lysophosphatidic acids or LPAs found in the small intestine. The small intestine produces small amounts of LPAs, which were once considered a minor factor in the production of LDL (bad) cholesterol in the blood.
The researchers found, however, that a high-fat, high-cholesterol diet fed to lab mice caused their levels of LPAs to spike with a two-old increase. Adding LPAs to a low-fat, low-cholesterol diet resulted in much the same increase in LPAs as putting the mice as a high-fat diet. Mice that were fed LPAs with a low-fat diet experienced changes in gene expression patterns leading to increases in LDL and decreases in HDL (good) cholesterol, along with increases in blood biomarkers seen in the mice fed a high-fat, high-cholesterol diet.
The evidence, say the researchers, points to LPAs in the small intestine playing a more important role in determining LDL and HDL cholesterol levels than previously considered. “Recognizing the importance of these minor lipids in the small intestine,” says Fogelman, “may lead to ways to reduce their levels and prevent abnormalities in blood levels of ‘good’ and ‘bad’ cholesterol that contribute to heart attack and stroke.”
The type of bioengineered tomatoes developed at UCLA and tested in the study contains a peptide known as 6F, which acts the same way as the protein apoA-1, a key ingredient in HDL cholesterol. The UCLA team added to the diets of the test mice a freeze-dried powder made from the engineered tomatoes equivalent to 2.2 percent of the low-fat diet, supplement with LPAs. The researchers also added an equivalent amount of the enhanced tomato powder to the mice’s high-fat diet.
The results show adding the powder from the peptide-enhanced tomatoes prevented an increase in LPA levels from occuring in the small intestines of the mice fed the LPA-added low-fat diet and the mice on a high-fat diet. Mice fed ordinary (non-engineered) tomatoes showed no difference in LPA levels.
The researchers say they next want to better understand the processes that are affected by LPAs in the small intestine. That work will involve identifying the small intestine genes altered by LPAs to uncover the signaling pathways that can serve as treatment targets.
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