U.S. Patent and Trademark Office. Alexandria, Virginia (A. Kotok)
10 September 2015. VolitionRx, a developer of blood tests to screen for cancer, received a U.S. patent for its underlying technology that detects changes in basic cell proteins found in blood. Patent number 9,128,086 was issued by the U.S. Patent and Trademark Office on 8 September to four inventors and assigned to the company, incorporated in Singapore, but operating from Namur, Belgium.
The patent covers techniques developed by VolitionRx for detecting indicators of disease based on the nature of histone proteins that form in the core of cells. DNA strands coil around histones and are condensed into chromatin, the material that makes up chromosomes. The pieces of DNA that wrap around histones are called nucleosomes, and when mutations form in the DNA, nucleosomes change as well, which affect the underlying histone proteins.
Changes in nucleosomes are unique for each disease condition, which makes it possible to identify the disease by a biomarker or indicator when that nucleosome change occurs. VolitionRx’s technology looks for those indicators in antibodies in blood and other fluid samples that bind to histones and appear when nucleosomes change. The patent applies to tests with this technology to detect cancer and autoimmune diseases, disorders where the immune system is tricked into attacking healthy cells rather than invading pathogens.
VolitionRx is developing tests for cancer using blood samples as small as a single drop. Its lead product tests for colorectal cancer, where screening for the disease today often requires an invasive and expensive colonoscopy. Yesterday, the company released interim results of a retrospective study of 4,800 individuals at 6 hospitals in Denmark who had colonoscopies, and later provided blood samples for analysis with the company’s test.
The results show the VolitionRx blood test detected 81 percent of the colorectal cancer cases, both in early and late stages, with 78 percent specificity, where those not having the condition were recorded as negative. The company’s test also detected 63 to 67 percent of pre-cancerous polyps, which included polyps at high risk of becoming a tumor. The company is presenting the study’s findings this week at industry and professional meetings.
VolitionRx is evaluating its technology in prospective studies of colorectal cancer, as well as current and planned studies of lung, ovarian, and prostate cancer. The company is also studying its blood test technology to detect endometriosis, a painful disorder affecting women where tissue normally found in the uterus begins growing outside the uterus in other organs. Diagnosing endometriosis usually requires a laparoscopy, a surgical procedure done under anesthesia.
9 September 2015. A coalition of three medical centers in the U.S. is leading a comprehensive research initiative to find treatments and eventually cures for amyotrophic lateral sclerosis, or ALS. The collaboration, known as Answer ALS brings together researchers from Johns Hopkins University in Baltimore, Cedars-Sinai Medical Center in Los Angeles, and Massachusetts General Hospital in Boston to amass a coordinated knowledge base about ALS across a range of disciplines, and make their findings freely available to colleagues worldwide to speed development of therapies.
ALS, also known as Lou Gehrig’s disease,is a progressive neurological disease that attacks the nerve cells controlling voluntary muscles, such as those in the arms, legs, and face. In ALS, muscles gradually weaken and waste away, leading to individuals losing their strength and their ability to move their arms, legs, and body. When diaphragm and chest wall muscles fail, people lose the ability to breathe without ventilatory support, often leading to death from respiratory failure.
Answer ALS plans to attack ALS from a number of perspectives, applying new developments in fields such as genomics, stem cells, big data analytics, precision medicine, and artificial intelligence. The project aims to deepen its basic understanding of ALS’s causes, develop cell models that reflect that understanding and screen for new therapy candidates, develop treatment protocols personalized to individual ALS patients, and discover therapies that slow or stop progression of the disease, leading to eventual cures.
The core of Answer ALS, say its organizers, is a massive personalized database of new ALS-specific information. Researchers expects to collect data from 1,000 ALS patients over time, with much of the clinical data coming from real-time monitoring of patients having wearable sensors and devices. Patients will also be asked to donate induced pluripotent stem cells, which will be combined with genomic data and their real-time monitoring. Bioinformatics experts plan to merge the data and generate algorithms, some based on machine learning, to analyze the collections for insights into ALS treatments.
Over the first two years of the project, Answer ALS expects to generate the stem cell lines differentiated into nerve cell and supporting (glial) cells in the brain, which will be analyzed by the founding medical centers and collaborators for underlying patterns in the genome and associated RNA and proteins. After two years, other teams will uncover subgroups within the ALS patient population for commonalities that can lead to clinical trials based on expected drug responses. Researchers will also seek out biomarkers for diagnostics and disease progression, as well as disease-causing pathways and drug targets.
Answer ALS plans to raise $25 million to finance the research, of which $20 million is collected so far. Funding is led by the Leandro P. Rizzuto Foundation and the Robert Packard Center for ALS Research at Johns Hopkins University. The Leandro P. Rizzuto Foundation sponsors ALS Finding a Cure, a fund-raising project for ALS.
Team Gleason, another ALS fund-raising effort, organized the first meetings leading to Answer ALS. The group is named for former NFL player Steve Gleason who lives with ALS. Major donors include the National Football League and PGA Tour, as well as financial services company Travelers whose chairman and CEO Jay Fishman was recently diagnosed with ALS.
“After being diagnosed with ALS,” says Fishman in an Answer ALS statement, “I looked for the most aggressive project with the greatest possibility of yielding results through rapid benchmarks and milestones. This was that project.”
9 September 2015. A survey of teens and young adults in the U.S. shows those who smoke electronic cigarettes are much more likely to start smoking tobacco within one year. Results of the study, conducted by a team from University of Pittsburgh and Dartmouth University medical centers, appear online in yesterday’s issue of the journal JAMA Pediatrics.
The researchers — led by Dartmouth pediatrics professor James Sargent and Brian Primack, director of Pittsburgh’s Center for Research on Media, Technology, and Health — sought to uncover connections between e-cigarettes and tobacco use among young people, particularly as they reach the age when these habits start forming. E-cigarettes are battery-powered nicotine delivery devices, that heat a liquid containing nicotine, moisturizing agents — propylene glycol or glycerol — and flavoring agents, as well as preservatives and artificial colorings.
Makers of e-cigarettes often market the devices as safer alternatives to tobacco-burning cigarettes and sometimes as a technique to help tobacco smokers quit conventional cigarettes. The authors cite evidence that e-cigarettes give off lower levels of toxic gases than burning tobacco, and among some smokers can reduce conventional cigarette use. More teens, however, are smoking e-cigarettes than conventional cigarettes and e-cigarette use is also increasing among young adults.
Sargent, Primack, and colleagues drew their data from a national survey of teenagers and young adults in the U.S., age 16 to 26, using landline and mobile telephone calls. The first wave of calls in 2012-13 yielded 694 respondents, who they contacted one year later. Participants were asked about their smoking behavior or intention to smoke, and were classified as nonsmokers or smokers, and among nonsmokers either susceptible or not susceptible to cigarette smoking.
All participants at the beginning of the survey did not smoke conventional cigarettes and were considered not susceptible to begin, as indicated by little interest or attraction to smoking. Of those participants, 16 or about 2 percent of all participants said they smoked e-cigarettes.
After one year, 6 of the 16 e-cigarette smokers (38%) progressed to smoking conventional cigarettes, compared to 10 percent of the remaining 678 participants who were not using either e-cigarettes or tobacco. Another 5 of the 16 original e-cigarette users (31%) expressed more of an interest or attraction to conventional cigarettes, although they had not yet started, compared to 9 percent of the original nonusers of e-cigarettes.
Primack says in a joint statement that these results hold up when accounting for demographic and environmental factors associated with smoking, noting “These differences remained statistically significant and robust even when we controlled for multiple known risk factors for initiating cigarette smoking, such as age, sex, race, ethnicity, socioeconomic status, sensation seeking, parental smoking and friend smoking.”
Regulating e-cigarettes is a complicated policy issue because of their potential to reduce the intake of toxic gases other than nicotine among established smokers. But Sargent points out that, “it is important to continue surveillance of both e-cigarettes and tobacco products among young people so policymakers can establish research-informed regulations to help prevent e-cigarettes from becoming gateway products on the road to youth smoking.”
From left: Wilfred van der Donk, first author and postdoctoral researcher Kou-San Ju, and William Metcalf (University of Illinois, Champaign)
8 September 2015. Researchers at University of Illinois in Champaign developed a technique using genomic tools to identify natural substances in bacterial strains with potential therapeutic properties. The team led by microbiologist William Metcalf and chemistry professor Wilfed van der Donk published its findings last week in Proceedings of the National Academy of Sciences(paid subscription required).
The Illinois team is seeking a faster and more systematic process for identifying promising drug candidates from a large pool of natural sources, that today requires tests on and examinations of extracts from individual compounds. In their paper, the researchers report on a technique they call genomic mining that systematically reviewed more than 10,000 actinomycetes, a type of bacteria, searching for phosphonates or phosphonic acids, natural signaling molecules with antimicrobial, antiviral, antimalarial, and herbicidal characteristics.
Because of these properties, phosphonates can be a good raw material for drug compounds. “Of the 20 previously known natural-product phosphonates, two are used commercially, one as a clinical antibiotic and one as an herbicide, says vand der Donk in a university statement, “and another one is now in clinical trials to treat malaria.”
In their paper, vanderDonk’s and Metcalf’s labs used high-throughput screening to analyze the genomes of the 10,000 microbes, looking for a specific gene known as pepM required to synthesize phosphonates. This analysis yielded 278 strains of actinomycetes with the pepM gene. The team then reviewed the 278 strains for the structure of their genomes, matching them against known compounds to discover new therapeutic candidates.
The results revealed a new pathway for production of phosphonates in these organisms, as well as 11 previously undescribed natural phosphonic acid products. One of the new discoveries is a compound the team calls argolaphos, an antibacterial candidate with potency against Salmonella typhimurium,Escherichia coli (E. coli), andStaphylococcus aureus, three major disease-causing microbes.
The researchers believe genomic mining can speed the drug discovery process with natural sources. Metcalf notes, “pharmaceutical companies would have done bioassays on extracts from all 10,000 species,” adding “It was very, very tedious and very expensive. That would have taken a large company with hundreds of people years, if not decades.”
8 September 2015. An early-stage clinical trial testing an implanted biocompatible plastic framework to encourage healing of spinal cord injuries completed its initial enrollment. The Neuro-Spinal Scaffold device is made by InVivo Therapeutics Holdings Corp. in Cambridge, Massachusetts.
Spinal cord injuriesare usually caused by a sudden, traumatic blow to the spine that bruises or tears into spinal cord tissue, resulting in fractures or compression to vertebrae, or in some cases severing of the spinal cord. Depending on severity, people with spinal cord injuries often suffer loss of feeling or motor function in the limbs, and in some cases complete paralysis. According to theNational Spinal Cord Injury Statistical Center, spinal cord injuries occur in 40 out of 1 million people in the U.S., adding some 12,500 new cases each year.
The Neuro-Spinal Scaffold, says the company, is designed for surgical implantation at the site of the injury, to provide structural support and a matrix on which new nerve cells can regrow. The scaffold’s framework is made of poly lactic-co-glycolic acid, or PLGA, a polymer material used in sutures that breaks down and absorbed into the body. The device is coated with poly-lysine, also a biocompatible polymer, used as a coating on culture dishes and slides that enhances electrostatic attraction of cell membranes, in this case to encourage regrowth of nerve cells.
The clinical trial is a pilot study to evaluate the safety and feasibility of the Neuro-Spinal Scaffold, as well as gather early clinical evidence of its efficacy. Researchers will look for adverse effects of any kind, and record changes in functional impairment using a standard measurement scale at several times over the 12 months following implantation of the device.
The study planned to enroll five patients and recruited its fifth patient at University of Southern California medical center in Los Angeles. Mark Perrin, InVivo’s CEO and chairman says in a company statement, “we intend to request expanding the number of patients in the current pilot study beyond five to further compress clinical timelines. We anticipate that we will receive formal approval of this expansion within the next two months.”
The technology underlying the biopolymer scaffolds and related therapies in development at InVivo is based on research by Robert Langer of MIT and Joseph Vacanti of Massachusetts General Hospital, affiliated with Harvard University, that InVivo licensed from the institutions. Langer is a scientific advisor to the company.
4 September 2015. A new challenge on InnoCentive is asking the public for a design of an efficient yet simple incinerator of medical waste generated during humanitarian emergencies. The competition has a total potential payout of $30,000 and a deadline for submissions of 4 November 2015.
InnoCentive in Waltham, Massachusetts conducts open-innovation, crowdsourcing competitions for corporate and organization sponsors, in this case Humanitarian Innovation Fund. Free registrationis required to see details of the competition.
Humanitarian Innovation Fund sponsoring the challenge supports organizations seeking to make the delivery of humanitarian aid more effective and cost-efficient. For this competition, the fund is tackling the problem of medical waste that piles up in humanitarian emergencies, such as floods and armed conflicts, particularly in low-resource countries.
Without a means of effectively destroying medical waste, affected populations face more exposure to infectious diseases and fouling of air, ground, and drinking water. In many cases, medical workers in the field during emergencies burn the waste in empty fuel drums, but they rarely work well and can cause problems with pollution. More durable medical waste incinerators can be brought in, but they are often expensive and need skilled staff to set-up and operate.
The sponsors are calling for a medical waste incinerator design that is simple, efficient, and durable. The device should be economical to operate in low-resource regions, easy to transport, and be assembled with local skills and materials. In addition, the incinerator must meet specific fuel and temperature requirements.
InnoCentive calls this type of competition a theoretical challenge requiring a written proposal that fleshes out an idea before it becomes a proven concept. Proposals submitted in a theoretical challenge usually offer detailed descriptions and specifications showing how the ideas would work. Humanitarian Innovation Fund indicates it expects written proposals to run about 10 pages.
Proposals will be reviewed by a panel of experts from humanitarian aid organizations such as Oxfam and Médecins Sans Frontières (Doctors Without Borders). The sponsor says it plans to award three prizes of $5,000 each to the top ideas generated in the competition. A separate bonus prize of $15,000 will also be awarded to a winning proposal that can be immediately turned into a working prototype device.
Humanitarian Innovation Fund asks competitors receiving awards to grant a non-exclusive license to their intellectual property. Sub-licensing of intellectual property is possible for further development or manufacturing of the solution.
4 September 2015. A synthetic antibody designed to prevent bleeding episodes among people with the most common type of hemophilia received a breakthrough therapy designation from the U.S. Food and Drug Administration. The pharmaceutical company Roche says FDA assigned the designation its biologic therapy code-named ACE910, now being tested in clinical trials.
Hemophiliais an inherited disorder, where the proteins needed to mix with platelets to allow blood to coagulate are missing. About 8 in 10 people with the condition have hemophilia type A, where the proteinclotting factor 8is missing. In type B, clotting factor 9 is missing.
ACE910 is an engineered, humanized antibody that simulates some of the functions of clotting factor 8, given once a week by injections under the skin. While ACE910 acts like factor 8, Roche says its structure does not generate reactions leading to formation of factor 8 inhibitors, a problem with traditional factor 8 replacement therapies. Formation of factor 8 inhibitors is a serious complication for some people with hemophilia, which makes control of their bleeding more difficult.
FDA assigns abreakthrough designationto therapies that address a serious condition and demonstrate through clinical evidence that the treatment is a substantial improvement over current methods. Once designated as a breakthrough therapy, a drug or biologic can receive early and frequent communications with FDA staff, quick resolution of questions, intensive guidance on drug development, and an organizational commitment from top managers.
The breakthrough designation was given to ACE910 as a preventive drug for people with hemophilia A and factor 8 inhibitors, based on an early-stage clinical trial with a small sample of individuals in Japan having severe cases of hemophilia A. The most recent report from the trial, given at a meeting of the International Society of Thrombosis and Hemostasis in June, shows ACE910 completely controlled bleeding in half of the participants (9 of 18) while receiving the therapy. Adverse effects among participants were considered mild or moderate, largely due to injection site reactions.
ACE910 was originally developed by Chugai Pharmaceutical Co. in Tokyo, and later licensed to Roche, which is now co-developing the therapy with Chugai. A late-stage clinical trial is planned to begin later this year among individuals with hemophilia A and factor 8 inhibitors. A separate trial with people having hemophilia A without factor 8 inhibitors is planned for 2016.
The two research labs — both in Toronto, Ontario, Canada — jointly developed a small molecule compound that in lab tests already shows promise in blocking growth of breast cancer cells and some types of acute myeloid leukemia. The molecule, code-named OICR-9429, targets and stops activity of WD repeat-containing protein 5 or WDR5 protein associated with a number of regulatory processes in the body affecting cell growth.
Developers of OICR-9429 already collaborated with labs in the U.S. and Austria to find targets for the therapeutic molecule. In a study published yesterday in the journal Nature (paid subscription required), a lab at University of Pennsylvania in Philadelphia discovered OICR-9429 can counteract mutations of the TP53 gene associated with a wide range of cancer types, and in the study sharply reducing proliferation of breast cancer cells.
In a study published on 20 August in Nature Chemical Biology (paid subscription required), a team led by researchers at CeMM Research Center for Molecular Medicine in Vienna, Austria applied OICR-9429 to mutations of the CEBPA gene associated with about 9 percent of cases of acute myeloid leukemia that expresses a protein that interacts with WDR5. In lab tests, the researchers found OICR-9429 inhibited growth of acute myeloid leukemia cells expressing the mutation-associated protein.
Developers of OICR-9429 want to see more of these studies and quickly, which is the reason for making OICR-9429 available to fellow researchers. “In the time that it would normally take to negotiate a legal agreement to provide OICR-9429 to other research teams,” notes Cheryl Arrowsmith, chief scientist at Structural Genomics Consortium in a joint statement, “we have received results back from our collaborators showing that it can kill two different types of cancer cells.”
By making OICR-9429 readily available and insisting on researchers sharing the results, Ontario Institute for Cancer Research and Structural Genomics Consortium say they hope to speed the identification of targets for the compound and build on the common experiences of teams testing the compound. The two organizations are collaborating on other therapeutic molecules with which they expect to apply these same development methods.
3 September 2015. Engineers and medical researchers at Columbia University developed a technique that delivers small amounts of medications in liquid form to specific areas of lungs. The team led by biomedical engineering professor Gordana Vunjak-Novakovic published its proof-of-concept findings earlier this week in Proceedings of the National Academy of Sciences (paid subscription required).
The Columbia team is seeking a method to more carefully target a small volume of drugs to treat lung diseases such as cystic fibrosis, pneumonia, chronic obstructive pulmonary disease (COPD), and lung cancer. Current techniques deliver drugs for the lungs systemically with pills or inhaled aerosols that require a large dosages of medications. The high volume is needed for the drugs to reach their targets, but the quantities can also cause adverse side effects.
Vunjak-Novakovic’s lab in New York studies lung regeneration with stem cells and bioengineering methods, which led to its work on drug delivery to this highly complex organ. Postdoctoral researcher Jinho Kim, the paper’s first author, tracked the flow of liquid in a lab model of lungs with glass tubing representing the channels and stages the compound passes from the airway down to the individual air sacs.
Kim and colleagues then developed a mathematical model of drug delivery with liquids designed to have lower surface tension for easier absorption by the air sacs, a technique used sometimes with premature infants having weak weak lungs. The team used the math model to simulate delivery of minute volumes of drugs, less than 1 milliliter, to various parts of the lung and under varying conditions of ventilation.
The researchers tested the process in lungs of lab rats, delivering less than 1 milliliter of drug and enzyme solutions, with fluorescence imaging to record the results. The findings show the technique can deliver these small quantities to specific areas of lungs, depositing a thin film of liquids on the targeted locations.
“We envision that our micro-volume liquid instillation approach will enable predictable drug concentrations at the target site,” says Vunjak-Novakovic in a university statement, “reducing the amount of drug required for effective disease treatment with significantly reduced side effects.”
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