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Common Antibodies Found for Multi-Virus Flu Vaccine

Vaccination

(U.S. Centers for Disease Control and Prevention)

22 July 2016. A team at National Institutes of Health discovered three types of antibodies that can neutralize a variety of influenza viral strains infecting humans. Researchers from National Institute of Allergy and Infectious Diseases and National Human Genome Research Institute published their findings yesterday in the journal Cell (paid subscription required).

The team led by Peter Kwong, John Mascola, and Adrian McDermott at NIAID are seeking a more robust strategy for flu vaccine design, which today requires creating a new vaccine formula every year to meet anticipated mutations in flu viruses. Because vaccines need a long lead time to develop a new formulation, manufacture sufficient quantities, and ship inventories were needed, health authorities often must guess well in advance at the precise targets for each year’s flu vaccine.

Most seasonal flu vaccines in the U.S. cover 3 or 4 strains or lines of the virus. In recent years those strains include H1N1 and H3N2 among the influenza A viruses, and 1 or 2 influenza B lines. Influenza A viruses have 11 different strains, while influenza B viruses have 2 main varieties. People older than 65 usually get a higher dose of the vaccine since between 80 and 90 percent of flu related deaths have occurred in people 65 years and older.

In the paper, the researchers took blood samples from 6 participants in a clinical trial testing a vaccine protecting against the H5N1 or avian flu virus, a strain of influenza A. From the samples, the team identified white blood cells, called B cells, in the immune system producing antibodies that reacted to the test vaccine. The researchers then genetically analyzed the antibodies from these reacting B cells.

Results of the analysis reveal 3 classes of antibodies capable of addressing a wide range of influenza A sub-types, from a common characteristic in their hemagglutinin proteins — the “H” in the influenza strain code. The stem in the crystalline protein structure of the hemagglutinin stem had a common binding area for antibodies. Thus various strains of influenza A viruses may have different protein structures, but the binding regions in the stems overlapped.

The researchers point out that a common binding region in the flu virus stem was found before, but only in humans developing antibodies resulting from a natural flu virus infection. These new findings indicate a common binding region covering a wide range of influenza strains could be induced with a vaccine.

As a result, the authors recommend using the sequencing data from these B cells as a benchmark for measuring the breadth of immune responses in future vaccine trials.

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Device Measuring Nerves on Heart Rhythm in Development

Peng-Sheng Chen

Peng-Sheng Chen (Indiana University)

22 July 2016. A spin-off enterprise from Indiana University is creating a device to measure sympathetic nerve activity — the fight-or-flight response — in people with heart rhythm disorders. Research and development of a prototype device, by Arrhythmotech LLC in Indianapolis, is funded by a new 2-year, $1.47 million grant from National Institute of Drug Abuse, a part of National Institutes of Health.

The device, known as neuECG, is a non-invasive technology to record sympathetic nerve activity and electrocardiogram measures with electrodes placed on the skin. The sympathetic nervous system responds to threats releasing neurotransmitter chemicals into muscle fibers, which can also affect heart muscles, resulting in atrial fibrillation, a condition marked by irregular heart rhythms. While some current techniques can measure sympathetic nerve activity, says Arrhythmotech, they provide only indirect readings or require invasive placement of sensors.

The research behind neuECG was done in the lab of Peng-Sheng Chen, director of Indiana’s cardiology institute. The lab’s research with animals shows an early version of the device with electrodes on or under the skin records sympathetic nerve activity that correlates closely with sensors on the stellate ganglion, a collection of sympathetic nerves in the throat. The university filed a patent application for the device.

Chen, with Indiana cardiology colleague Shien-Fong Lin, founded Arrhythmotech in 2014 to commercialize the technology. The company received a Small Business Technology Transfer or STTR award to establish the feasibility of the neuECG device in humans. The new funding will enable Arrhythmotech, directed by Thomas Everett, another Indiana cardiologist and the company’s chief scientist, to develop working prototypes of the technology for human clinical trials.

Under the new award, the company will validate an neuECG prototype in a clinical study at Cedars-Sinai Medical Center in Los Angeles. Arrhythmotec plans to test the device as well in research at the Mayo Clinic with lidocaine injections into or removal of the stellate ganglia to control sympathetic nerve activity. Lidocaine is a local anesthetic also given to control irregular heart rhythms. In addition, the company expects to test the feasibility of sympathetic nerve activity as a biomarker of vulnerability for atrial fibrillation.

Chen and colleagues formed Arrhythmotec as part of the university’s SpinUp program encouraging scientists to become entrepreneurs. In 2015, the company was one of the finalists in the annual BioCrossroads New Venture Competition, a statewide contest among start-up life sciences enterprises.

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Online Concierge: A New Service Shows the Way

– Sponsored content –

California Academy of Sciences

California Academy of Sciences, an attraction offered through Way.com (calacademy.org)

21 July 2016. Many upscale hotel properties offer a concierge service, where experts on the local scene recommend restaurants, attractions, events, and transportation advice in the cities visited, and in some cases even make reservations. On the other hand, those of us who travel without ever seeing a concierge, probably most travelers, must fend for ourselves. Now we’re no longer on our own; Way.com provides many of those same amenities from our computers or mobile devices.

Way.com bills itself as an online concierge service providing reservations for dining, entertainment, attractions, and parking for travelers and locals alike. Founders Binu Girija and Bhumi Bhutani started Way.com in the San Francisco Bay area in January 2013, and the company is still located in that region at Fremont, California.

The site brings together member customers seeking these services with commercial providers. Registering as a customer or a provider is both free of charge. Signing up as a customer is simple, requiring a minimum of details. Signing on can be done with an e-mail address or with a Google+ or Facebook ID.

As of July 2016, the service is accessible over the Web with computer and mobile versions. The company says a mobile app is in development, and members can request an alert when it’s available.

Way.com signed up providers in San Francisco and a number of other U.S. cities, with New York, Los Angeles, San Diego, Chicago, Boston, Miami, Philadelphia, Houston, and Dallas featured on its Web site. Atlanta and Orlando in the U.S., and Toronto and Montreal in Canada are also in the works. Way.com is signing up vendors as well beyond those cities, which can be viewed by entering the city name in its search box.

The company says a key feature of its site is the ability to bundle a number of related services into one transaction. A couple seeking an evening on the town, for example, can make dinner reservations and book movie tickets with Way.com, as well as find space in a parking garage. Other more specialized services would require separate transactions.

One attraction in San Francisco I’ve always wanted to visit is the California Academy of Sciences in Golden Gate Park, but never quite had the time during several hurried business trips. Tickets to the California Academy of Sciences are available through Way.com. I picked out a date, and selected two senior-citizen e-tickets (yes, I’m that old), which were additionally discounted from the list price. The shopping cart came up quickly, and allowed for payment with Visa, Mastercard, or Discover card. Deleting items from the shopping cart was also one easy step.

In addition, Way.com has a loyalty program called Way Bucks, which like any reward program, lets you accumulate points for purchases. Way Bucks points are calculated with what the company calls an earn percentage, up to 10 percent, of the purchase amount. Most items in its inventory, says Way.com, qualify for Way Bucks.

Since starting up in 2013, Way.com attracted some 100,000 users in all 50 states. Its event tickets inventory exceeds $2 billion, according to the company, supporting more than 30,000 events. Way.com says as well that it’s the largest parking provider in the Bay area.

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Study to Evaluate Blood Pressure Diagnostics

Measuring blood pressure

(Wikimedia Commons)

21 July 2016. A health care system in Seattle is assessing three different techniques for confirming newly found cases of hypertension, or high blood pressure. A research team from Group Health Research Institute, the research arm of Group Health Cooperative, a network of health care providers, is conducting the study, funded by a $2.8 million grant from Patient-Centered Outcomes Research Institute, or PCORI.

The team directed by Group Health researcher Beverly Green is seeking easy and reliable ways of confirming an initial diagnosis of high blood pressure, a condition affecting some 70 million people in the U.S., about 1 in 3 adults. However, only about half (52%) of people with high blood pressure have their condition under control, according to Centers for Disease Control and Prevention. Without controlling high blood pressure, the condition increases the risk of heart disease and stroke, among the leading causes of death in the U.S.

Confirming the initial screening is an important next step, however, since about 3 in 10 people first found with high blood pressure in the clinic turn out to have normal levels outside the clinic, a phenomenon known as “white coat hypertension,” often a result of the stress of being tested. To confirm the initial diagnosis, the U.S. Preventive Services Task Force recommends monitoring an individual’s blood pressure for 24 hours, with readings taken every 30 minutes during the day and every 60 minutes at night. Home monitoring with a blood-pressure cuff for several days is offered by the task force as an option.

Green and colleagues note that continuous, ambulatory blood pressure monitoring is rarely requested of patients, although monitoring at home is more accurate and practical with today’s technology, and kiosks with equipment to check blood pressure are found more often in drug stores and supermarkets. The team plans to evaluate these measurement options in its study.

The researchers expect to recruit 510 adult Group Health patients found with high blood pressure in their initial screening, and randomly assign them to 1 of 3 methods for confirmation: testing at a clinic, at home, or with a public testing kiosk. Each of these methods will then be compared to continuous ambulatory blood-pressure monitoring.

“Correct diagnosis of hypertension is important to prevent strokes, heart attacks, and heart failure,” says Green in a Group Health statement, “and also to avoid making people worry or take medicines when they don’t need to.”

Group Health says the formal award announcement will be made after a review by PCORI of the study’s business plan. On Tuesday, PCORI announced awards of nearly $153 million for 28 comparative clinical effectiveness research projects.

The Group Health researchers may not be aware of the latest innovations in ambulatory blood pressure monitoring. In June, Science & Enterprise reported on development of a wristband device for continuous blood pressure monitoring called Slapband, by recent graduates from University of California in Irvine.

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Cancer Center Tests Mobile Patient Tracking

Woman with smartphone

(kaboompics.com/Pexels)

20 July 2016. Memorial Sloan Kettering Cancer Center in New York is evaluating mobile devices to track the quality of life experienced by multiple myeloma patients. The cancer center is partnering with Medidata Solutions, a provider of cloud-based analytics for clinical research, also in New York.

Multiple myeloma is a cancer of plasma cells, white blood cells helping fight infections by making antibodies that recognize invading germs. The disorder causes cancerous cells to accumulate in the bone marrow, crowding out healthy plasma cells. Instead of antibodies, the malfunctioning cancer cells produce abnormal proteins that cause kidney problems and other disorders.

Memorial Sloan Kettering says it treats more than 400 patients a year with multiple myeloma or related plasma cell diseases. Patients with this type of cancer receiving chemotherapy will be offered an opportunity to take part in the study, where they will wear an activity tracker, and capture data on their smartphone. In addition to physical activity, patients will record fatigue, appetite, and other quality-of-life measures.

Participants in the study will first wear the activity tracker for up to 7 days to establish a baseline, then continuously for 4 months, covering 4 cycles of therapy. Data will be captured in Medidata’s Patient Cloud app, with its ePro feature for patient-entered information and SensorLink that integrates data from apps in Medidata’s Clinical Cloud. The app is available for free from iTunes and Google Play app stores.

Medidata’s Clinical Cloud is the company’s software-as-a-service platform for data collection and analytics for clinical trials. Medidata says its Clinical Cloud databases already store 8 billion records from 2 million patients enrolled in 9,000 studies.

Memorial Sloan Kettering already offers a mobile app, known as Mobile MyMSK, for its patients. The app, available only in an iPhone version, tracks medications, symptoms, side effects, lab and radiology test results, and appointments. The app also has messaging, reports, and directory functions.

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Software Developed to Quantify Single Cells Over Time

Tracking tool screen shot

Screen shot from The Tracking Tool showing cell lineage tree (ETH-Zurich)

20 July 2016. A team of computational biologists and engineers in Europe developed software that analyzes the growth and changes in individual cells over time. Researchers led by Fabian Theiss of the Helmholtz research center in Munich, Germany and Timm Schroeder at ETH technical university in Zurich, Switzerland described their software last week in the journal Nature Biotechnology (paid subscription required).

Theiss, Schroeder, and colleagues are seeking better tools for tracking and measuring properties of individual cells, particularly over extended periods of time. For example, stem cells are being used more frequently for designing new treatments and regenerating tissue, but most existing software is designed for data snapshots of cellular development at various points of time, not for continuous measurements.

A particular challenge in solving this problem is the enormous amounts of data generated. “On the one hand, it is necessary to take enough images in order not to lose track of the cells,” says Theiss in a Helmholtz center statement, “while on the other hand, this results in enormous data quantities, in some cases with millions of images.” Theiss is director of the center’s Institute of Computational Biology and chairs mathematical modeling of biological systems at Technical University of Munich.

Theiss and Schroeder, now a professor of biosystems science and engineering at ETH-Zurich and previously a researcher at Helmholtz center in Munich, took a modular approach for their software. “We put together two separate packages,” notes Schroeder, “a manual tracking tool and a semi-automatic quantification tool for individual cell analyses in time-lapse microscopy movies. The two together allow measurements of properties such as the length of the cell cycle, the expression dynamics of certain proteins, and correlations of these properties between sister cells.”

Schroeder’s cell systems dynamics research group at ETH-Zurich — located in Basel, Switzerland — studies complex cell systems, particularly mammalian stem and progenitor cells. He and his colleagues are developing tools for long-term imaging, tracking and quantification of individual cells and their cellular and molecular behavior in cultures. Those investigations, says the lab, requires work in cell and molecular biology, as well as imaging, engineering, software development, statistics, and mathematical modeling.

The two software packages, The Tracking Tool (tTt) and qTfy, as well as the source code, can be downloaded from the ETH-Zurich web site. The software is made available under a GNU general public license.

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Genetic Disease Biotech Gains $55M in Early Funds

Genomics graphic

(National Human Genome Research Institute, NIH)

19 July 2016. A biotechnology start-up developing therapies for genetic diseases through regulation of genetic processes is raising $55 million in its first venture funding round. Fulcrum Therapeutics in Cambridge, Massachusetts is being established and initially financed by Third Rock Ventures, a venture capital company in Boston backing new scientifically-based enterprises.

Fulcrum Therapeutics is integrating technologies that regulate gene expression and transcription with computational biology to discover therapies at first for stubborn inherited diseases. The company’s initial targets are Fragile X syndrome and facioscapulohumeral muscular dystrophy, or FSHD. Each disease arises from a mutation resulting in errors in the regulation or expression of critical genes.

Fragile X syndrome affects learning and cognitive development in children, mainly boys, affecting speech and language, and resulting in symptoms similar to attention deficit disorder and autism spectrum disorder, as well as seizures. In Fragile X syndrome, a mutation silences the FMR1 gene that instructs the production of proteins needed for development of synapses, the signaling elements of nerve cells.

FSHD is a neuromuscular disease resulting in progressive weakness and atrophy of facial and shoulder muscles, usually in older children and teens. Children with FSHD often have difficulty sipping drinks through a straw, eyes that do not close completely, asymmetric shoulder development, and difficulty raising arms above the shoulder. In FSHD a mutation activates the DUX4 gene that should be silenced, which is believed to influence activity of other genes affecting muscle development.

Fulcrum Therapeutics expects to discover and develop small molecule, or low molecular weight, therapies affecting the on/off genetic switches for disorders like Fragile X syndrome and FSHD. The company plans to tap into advances in cell biology, including induced pluripotent stem cells, combined with concepts of precision medicine from genetics, as well as high-volume computational techniques to screen big data sets and identify drug targets.

The company says its technology reflects advances in genetics and medicine from its scientific founders:

Bradley Bernstein, professor of pathology, and director of the Epigenomics Program at the Broad Institute of MIT and Harvard

Michael Green, professor of molecular medicine at University of Massachusetts Medical School, and director of the school’s cancer center

Rudolf Jaenisch, professor of biology, and founding member of the Whitehead Institute for Biomedical Research at MIT, who works with stem cells and epigenetics

Jeannie Lee, professor of genetics and pathology at Harvard Medical School and molecular biologist at Massachusetts General Hospital

Danny Reinberg, professor of biochemistry and molecular pharmacology at New York University medical school

“One of the single most important biologic breakthroughs of the last decade has been the unraveling of gene regulation at a molecular level” says Fulcrum CEO Robert Gould in a company statement. “The richness of the human genome comes from the way genes are turned on and off. Through the modulation of these on and off switches we have the potential to transform the treatment of hundreds of serious human diseases.”

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Stem Cells, Gene Therapy Produce Replacement Joint Cartilage

Guilak and Ross with prototype hip replacement

Farshid Guilak, right, and co-author Alison Ross show prototype of living hip replacement (Robert Boston, Washington University in St. Louis)

19 July 2016. A process combining stem cells, industrial weaving, and gene therapy to grow replacement joint cartilage for osteoarthritis is shown in lab tests to also prevent inflammation from returning. A team from Washington University in St. Louis and biomaterials company Cytex Therapeutics in Durham, North Carolina demonstrate their technology in yesterday’s issue of Proceedings of the National Academy of Sciences (paid subscription required).

Researchers from the lab of orthopedic surgery professor Farshid Guilak at Washington University’s medical school are seeking better ways to treat osteoarthritis, the most common form of arthritis, affecting some 27 million people in the U.S. Symptoms often appear gradually and become worse with age, but are aggravated by overuse, obesity, previous injuries, and in some cases genetics. Treatments for osteoarthritis usually aim at relieving pain, since no cure is yet found.

While osteoarthritis affects mainly older individuals, it can occur in people as young as 25. The techniques developed by Guilak and colleagues are designed primarily for younger people with the condition, for whom normal joint replacement surgery would be a temporary solution, since replacement joints do not last more than 20 years. Another replacement surgery runs risks of bone damage and infection.

In their paper, the team created a synthetic, hip ball joint made from poly-epsilon-caprolactone, or PCL, fibers, a long-lasting biocompatible polymer. The fibers are woven into 3-D hemispheric scaffolds, about 22 millimeters in diameter, with the structure and properties of cartilage using industrial weaving techniques adapted by Cytex Therapeutics. Cytex is a spin-off enterprise from Duke University in Durham; Guilak is also president of Cytex and formerly a faculty member at Duke.

The fiber scaffolds are then seeded with stem cells derived from adipose or fat tissue from the patient, thus removing the risk for immune rejection. The stem cells are cultured and induced to develop into cartilage, which can replace the patient’s damaged cartilage.

The researchers took the process one step further. The team also coated the PCL fibers with Interleukin-1 Receptor Antagonist or IL-1Ra genes, using benign viruses to deliver the genes, which were transferred into the stem cells. IL-1Ra genes have anti-inflammatory properties blocking signals from Interleukin-1 proteins that promote inflammation.

In lab tests, the team tested identical synthetic cartilage samples treated with Il-1 proteins. The cartilage sample without IL-1Ra genes expressed inflammatory enzymes, while the cartilage receiving the IL-1Ra genes did not produce those enzymes.

“We’ve developed a way to resurface an arthritic joint using a patient’s own stem cells to grow new cartilage,” says Guilak in a university statement, “combined with gene therapy to release anti-inflammatory molecules to keep arthritis at bay. Our hope is to prevent, or at least delay, a standard metal and plastic prosthetic joint replacement.”

The researchers say they began tests of the technology with lab animals, and expect human clinical trials could start in 3 to 5 years.

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Nanotech Imaging Start-Up Raises $3M in Seed Financing

Tracking with magnetic nanoparticles

Tracking injected mesenchymal stem cells in lab mouse with magnetic nanoparticles (Magnetic Insight Inc.)

18 July 2016. A spin-off enterprise from University of California in Berkeley, developing a medical imaging technology with magnetic nanoparticles, is raising $3 million in start-up funding. Magnetic Insight Inc. in Alameda, California says the new financing supplements the $12 million it already raised before start-up.

The company licenses a technology developed in the UC-Berkeley lab of engineering professor Steven Conolly that detects magnetic tracers made with nanoscale particles — 1 nanometer equals 1 billionth of a meter — sent into tissue to diagnose medical conditions. Conolly is a co-founder of Magnetic Insight and a scientific advisor, with company CEO Anna Christensen and chief technologist Patrick Goodwill. The company began initially at StartX, an accelerator for start-up enterprises related to Stanford University; both Conolly and Goodwill got graduate degrees at Stanford.

Magnetic Insight’s technology sends non-radioactive and non-toxic iron oxide nanoparticle tracers into tissue, where they are detected by a magnetic field. Superparamagnetic iron oxide or SPIO particles, as small as 60 nanometers, are already used as contrast agents for MRI scans. Because iron oxide in the particles is not found in the body, the particles can be traced with a high degree of accuracy.

The magnetic field can also direct the movement of nanoparticles, with a location and direction determined by a free field point. When the magnetic direction of the nanoparticle changes, it sends a signal detected by a receiver. Those signals can then be aggregated and displayed as a quantitative image. Conolly with colleagues at Berkeley and Magnetic Insight demonstrated the technology tracking stem cells in lab mice in a paper published in January 2016.

The new financing is seed-round funds led by Sand Hill Angels, a group of Silicon Valley investors supporting innovative start-ups in Internet, information technology, clean tech, consumer, and life sciences. The StartX Fund and other angel investors participated in the financing. Magnetic Insight says it already raised some $12 million in research funding, prior to company start-up, as well as Small Business Innovation Research grants from NIH.

The new funding is expected to support development of Momentum, the company’s lead product. Momentum is a magnetic nanoparticle imaging system designed for preclinical applications, including cell tracking, monitoring vascular functions, cancer, and immunology research. The company also markets Vivotrax, magnetic particle imaging tracers for research, not clinical use.

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Stem Cell Treatments Show Benefit for ALS Patients

Nerve cells illustration

(commonfund.nih.gov)

18 July 2016. A clinical trial testing the safety of treatments derived from patients’ stem cells also shows patients with amyotrophic lateral sclerosis, or ALS, were able to slow the progression of their disease compared to those taking a placebo. Early results of the trial were reported by BrainStorm Cell Therapeutics Inc., in Petach Tikvah, Israel, developer of the treatments.

ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder where neurons or nerve cells controlling muscles in the body begin to waste away, and can no longer send or receive signals from the brain or spinal cord. As the nerve cells stop functioning, the muscles in the limbs, and later speech and breathing muscles, begin weakening and eventually stop functioning. Most people with the disease die of respiratory failure.

BrainStorm’s NurOwn technology, licensed from Tel Aviv University, extracts stem cells from the patient’s bone marrow that are transformed into cells supporting development of nerve cells. These transformed stem cells, says the company, secrete proteins called neurotrophic factors that protect nerve cells, as well as encourage their growth and interactions with muscles. Because the original cells come from the patient, they have little risk of rejection by the immune system.

The clinical trial is an intermediate-stage study conducted at 3 sites in the U.S. Some 48 patients with ALS were randomly assigned to receive either a single NurOwn treatment or a placebo. The trial’s primary objective is to test for the treatments’ safety and tolerability. However, the study team also recorded indicators of efficacy, namely a rating scale measuring decline of various muscle and communications functions, and slow vital capacity, a measure of normal respiratory function, before the treatments and at 10 points over 24 weeks.

BrainStorm reported results from the functional rating scales, specifically changes in scores as marked on a graph over time, where changes in the slope of the curve recording the functional decline can be precisely measured. The results show smaller declines in function, as measured by the slope of the curve over 24 weeks, for patients receiving NurOwn treatments, both in the point scores on the scale and percentages, from before the treatments, compared to patients receiving a placebo.

The company also broke out for a separate analysis ALS patients with a faster rate of decline from the disease — about half of the participants — since those with a slower rate of decline would likely experience a smaller benefit from the treatments.  Among patients with faster progressing disease, those receiving the stem cell treatments show higher functional rating scale percentages at each testing point, than patients receiving the placebo.

BrainStorm says the treatments were largely safe and well-tolerated, with adverse events considered mild or moderate. Participants receiving NurOwn and placebo treatments experienced some kind of reaction, with adverse events happening somewhat more frequently among those receiving stem calls than placebo recipients. Adverse events included local treatment site and back pain, fever, headaches, and joint pain. No deaths were reported and all patients completed the trial.

The results, say BrainStorm, show the company can proceed on a late-stage study, with a larger patient population and multiple treatments.

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