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.
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.
Opioidswork 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 byCenters for Disease Control and Preventionas 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 antidotenaloxone, 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 andpriority reviewfrom 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.
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.
(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 calledmolecular intelligencethat 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.”
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 toCenters 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.
Triangular gold nanoparticles in microRNA sensor (Indiana University-Purdue University Indianapolis)
17 November 2015. Biochemical and medical researchers developed a technique for sensitive detection of RNA in humans that in lab tests can distinguish between benign conditions and cancer. The team from the lab of chemistry professor Rajesh Sardar at Indiana University-Purdue University Indianapolis published its findings in this month’s issue of the journal ACS Nano.
Sardar’s team, with colleagues from Indiana University’s medical school, were seeking a low-cost, reusable technology to detect pancreatic cancer with microRNAs in blood. MicroRNAs are small non-coding molecules of ribonucleic acid, or RNA, that regulate gene expression by larger RNA molecules. MicroRNAs may directly influence as many as 30 percent of genes in the entire human genome, and play a role in cancer, diabetes, and cardiovascular diseases.
Pancreatic canceris often difficult to diagnose in its early stages, because of few unique symptoms associated with the disease, and because the pancreas is hidden among other organs in the body. As a result, it is often diagnosed in later, more advanced stages of the disease, with generally a poor prognosis for survival.American Cancer Societyestimates nearly 49,000 people in the U.S. will be diagnosed with pancreatic cancer this year, leading to more than 40,000 deaths.
The IUPUI team designed its sensor as a glass chip with gold triangle-shaped nanoparticles having surface plasmon resonance properties that use optical factors to measure the holding of biomaterials on the gold surface. Those properties make it possible to identify different patterns or signatures of microRNAs in blood and other fluids.
In lab tests, the researchers dipped their sensor chip in exosomes — tiny lipid-membrane containers in cells that gather up and secrete cytoplasm, the gel-like material outside the cell nucleus — derived from blood plasma looking for a microRNA signature identifying pancreatic cancer known as microRNA-10b. The team performed these tests with plasma from people with pancreatic cancer, healthy individuals, and people with pancreatitis, a non-cancerous inflammation of the pancreas. The results showed the sensor found reliably higher numbers of microRNA-10b in the samples from cancer patients, than the other two groups.
Testing for microRNAs today requires polymerase chain reaction technology that detects DNA fingerprints in samples. Sardar says the gold nanoparticle approach is simpler and less expensive, even when using gold. He notes in a university statement that “$250 worth of gold makes 4,000 sensors. Four thousand sensors allow you to do at least 4,000 tests. The low cost makes this technique ideal for use anywhere, including in low-resource environments in this country and around the world.”
The university says a patent has been filed for the technology.
17 November 2015. A new biotechnology company developing therapies that use tiny cellular containers to deliver their payloads is spun off from M.D. Anderson Cancer Center and raising $80 million in early venture funding. Codiak Biosciences, based in Cambridge, Massachusetts is founded and licensing research by Raghu Kalluri, chair of M.D. Anderson’s cancer biology department.
Kalluri’s lab studies exosomes as communication vehicles between cells. Exosomesare vesicles, tiny — 40 to 150 nanometer — lipid-membrane containers in cells that gather up and secrete cytoplasm, the gel-like material outside the cell nucleus. While originally believed to carry out waste removal and other maintenance tasks, exosomes were shown in recent years to perform useful delivery functions carryingproteins and genetic materialto other cells, and drawing increased attention from a range of biological disciplines.
As more of these delivery functions were revealed, researchers focused initially on opportunities provided by exosomes as biomarkers for diagnosing disease. In June 2015, for example, Kalluri and colleagues published research showing the potential of exosomes as early indicators of pancreatic cancer. Researchers are also investigating exosomes’therapeutic potential, such as delivering antigens to trigger immune reactions from T-cells. A number ofclinical trialsare currently testing exosome therapies with humans, mainly for cancer.
Codiak plans to develop both therapies and diagnostics for cancer and other disorders based on exosomes. The company is part of VentureLabs, the life sciences incubator of venture capital firm Flagship Ventures in Cambridge that aims to draw on synergies of similar portfolio enterprises. In addition to licensing Kalluri’s research, Flagship is merging VL27, one of its current portfolio companies developing exosome technologies, and its intellectual property into Codiak.
Flagship Ventures and Arch Venture Partners are leading Codiak’s early financing, raising $80 million in what the parties are calling the company’s first two funding rounds. Participating in the financing are Fidelity Management and Research Company, the Alaska Permanent Fund, and Alexandria Venture Investments.
Codiak is co-founded by Eric Lander, president and founding director of the Broad Institute of the Massachusetts Institute of Technology and Harvard University, as well as professor of biology at MIT and professor of systems biology at Harvard Medical School. Douglas Williams, also a co-founder, is Codiak’s president and CEO. Williams served as executive vice president for research and development at the biotechnology company Biogen from January 2011 to July 2015.
16 November 2015. The veterinary medicines company Zoetis is sponsoring a study of pain management and quality of life in dogs with osteoarthritis, using a mobile health monitor worn by the dogs. The 900 dogs serving as subjects in the study will wear the health monitor collar made by Voyce, known officially as i4C Innovations, a subsidiary of Intersections Inc. in Chantilly, Virginia.
The study expects to generate data on the ability of dogs to cope with osteoarthritis, a degenerative disorder brought about by deterioration of the cartilage surrounding their joints. Symptoms include deceased activity levels, stiff gait, and lameness, particularly in cold weather. Older dogs are most at risk of osteoarthritis, which can also be caused by trauma, abnormal development of hips or knees, obesity, or diabetes.
Dogs taking part in the study will wear the Voyce Pro health monitor, a device worn like a collar, for one year. The monitor uses non-invasive sensors to measure several health indicators: resting heart rate, resting respiratory rate, activity and intensity of activity, quality of rest, and distance traveled. The monitor connects via Wi-Fi to a pet health management system for pet owners, and the data are collected by veterinarians through separate database. Voyce says the device was developed by biomedical engineers and veterinary experts at Cornell University and elsewhere.
The Zoetis team will gather data from the monitors showing indicators of pain being suffered by dogs with osteoarthritis and its effects on their day-to-day lives. Those indicators include activity levels, intensity of activity, resting heart rate, and sleep disruptions, collected in the dogs’ home environments. “The ability to gather reliable information is critical when conducting studies, especially involving animals who may be in pain or struggling,” says Zoetis researcher Andrea Wright in an Intersections statement.
Intersections launched the Voyce Pro service for veterinarians in July 2015. The monitors themselves are available through veterinary hospitals. Zoetis offers several products to relieve pain in animals, as well as joint health products for dogs.
16 November 2015. Umeå University and the pharmaceutical company Prometic are partnering on development of new treatments for chronic wounds, such as diabetic foot ulcers and bed sores. The agreement gives Prometic, in Laval, Quebec, Canada an exclusive license to the university’s research on the blood plasma protein plasminogen, with the company funding further studies at Umeå University, in Sweden, on plasminogen. Financial terms of the deal were not disclosed.
Chronic wounds are often slow to heal because of inflammation and other factors that inhibit the healing process. One of those factors is diabetes that reduces blood flow to thelegs and feet, leading to nerve damage and reduced feeling in those regions, as well as slower healing of wounds.CDCsays in 2008, some 70,000 Americans required amputation of a leg or foot because of complications from diabetes. In addition, says CDC, people with diabetes are 8 times more likely to lose a leg or foot than people without diabetes.
At Umeå, the lab of Tor Ny, professor of biochemistry and biophysics, is studying the protein plasminogen, made in the liver and a regulator of inflammation that interrupts the repair of tissue and healing of wounds. Ny’s research with plasminogen in lab animals shows the protein, an enzyme precursor, sends signals to wound regions that reduce inflammation in its early stages, allowing wounds to heal faster. Pilot studies by Ny and colleagues with humans show plasminogen injections around wounds activate and stimulate healing.
At the same time, Prometic is developing protein-based therapies including treatments for plasminogen deficiencies in children. The agreement calls for a research collaboration between Prometic and Umeå University, funded by Prometic, which gives the company an exclusive license to technologies based on Ny’s research with plasminogen. Any further discoveries from the collaboration will also become the property of Prometic. The partnership will be managed from Umeå’s side by Omnio AB, a biotechnology spin-off enterprise from the university founded by Ny.
In addition, the deal calls for Umeå researchers to get access to Prometic’s clinical grade plasminogen developed by the company for clinical trials. “The fact that ProMetic’s plasma-derived plasminogen drug has already been proven safe and efficacious in humans,” says Ny in a Prometic statement, “combined with our own clinical experience in hard-to-treat wounds gives us great confidence as to the success of the upcoming wound healing clinical program,” expected to begin in the second half of 2016.
RNA molecule illustration (Nicolle Rager Fuller, National Science Foundation)
13 November 2015. In a new challenge on InnoCentive, a pharmaceutical company specializing in skin disorders is seeking a new minimally-invasive procedure for skin biopsies to provide samples for RNA analysis. The competition, sponsored by Leo Pharma in Ballerup, Denmark has a purse of $30,000 and a deadline of 10 February 2016.
InnoCentive in Waltham, Massachusetts conducts open-innovation, crowdsourcing competitions for corporate and organization sponsors.Free registrationis required to see details of the competition.
Leo Pharma develops medications for skin diseases including psoriasis, acne, eczema, skin infections, and non-melanoma skin cancer. The company notes that these conditions often create a good deal of physical and social discomfort for people, and its scientists in many cases consult behavioral scientists to develop medications that are easy and comfortable to administer.
Leo Pharma is seeking a new procedure for taking skin biopsies, samples of surface skin and underlying tissue for diagnosing disorders where changes in skin condition are symptoms. Skin cancer and actinic keratosis, a precancerous condition, are examples of disorders where skin biopsies are taken. According to Mayo Clinic, there are currently three main types of skin biopsies: shave biopsy that uses a razor-like device to take a sample of surface skin, punch biopsy that takes a circular sample of surface skin and underlying tissue, and excisional biopsy that uses a scalpel to remove an area of abnormal skin including underlying fatty layers if needed.
In this challenge, Leo Pharma is requesting ideas for a skin biopsy to provide a sufficient sample to conduct an RNA profile. RNA, short for ribonucleic acid, carries instructions for cells from an individual’s DNA or genetic code, and thus can be an indicator of the state of genes producing the RNA. Taking skin samples for RNA analysis, however, is difficult because of the invasiveness of current biopsy procedures, which sharply limits their use.
Thus, the company is seeking a minimally invasive technique causing less pain and tissue damage. One immediate benefit of a new less-invasive technique would be clinical trials that could use skin biopsies for RNA analysis more frequently and get results faster.
InnoCentive calls this type of competition a reduction-to-practice challenge that requires a detailed explanation of the proposed solution and a prototype for testing. Detailed instructions for preparing documents and prototype are provided for registered participants in the competition. The sponsor will review submissions on a rolling basis, and advise competitors to ship prototypes for testing.
Leo Pharma says current products on the market will not be accepted in the challenge, but changes to existing products will be considered. The company is asking for winning competitors to grant a non-exclusive license to practice their solutions. An exclusive transfer of intellectual property rights will not be required.
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