Accent Therapeutics, headquartered in Cambridge, Massachusetts, closed on a $40 million Series A financing. The round was funded by The Column Group, Atlas Venture and EcoR1 Capital.
Accent will focus on the fairly new area of epitranscriptomics—how RNA structure, stability, function and translation is involved in various diseases. In short, investigating how genes are turned on and off and how their activity is regulated.
RNA, especially messenger RNA (mRNA) function as go-betweens for DNA and the cells’ protein-manufacturing processes. Xconomy writes, “But before the cell makes proteins from RNA, it harnesses a variety of enzymes to attach or remove chemical groups from the RNA. These chemical modifications don’t affect the sequence of the RNA molecule, but they do change the RNA’s molecular structure, stability and function. This can ultimately affect how much protein is made from a particular mRNA. This gives the cell another control knob to turn when it wants to fine-tune the activity of a gene.”
Researchers with Accent recently published an overview of their work in Nature Reviews Drug Discovery with the title, “RNA-Modifying Proteins as Anticancer Drug Targets.” RNA-Modifying Proteins are referred to as RMPs.
The company’s founders include Howard Chang, Standford University; Chuan He, the University of Chicago; and Robert Copeland, president and chief scientific officer of Accent. Copeland said in a statement, “Epitranscriptomics opens a rich new target space, including RMPs that are associated with specific cancers, many with poor patient prognoses. We plan to treat patients by precisely targeting cancers that are uniquely dependent on these specific RMPs.”
Maps of the human epitranscriptome, which show the spots on mRNA molecules where there have been chemical modifications, only first began to be published in 2012. What these changes do, specifically, are still being determined, and are thought to be potential targets for disease modifying therapeutics. Some have already been impliciated in cancer.
The science is very new, which will leave Accent Therapeutics with plenty of basic research to do as it works to develop possible therapeutics. In addition to determining specific mRNA sites and what they do, it will work to identify and develop small molecule drugs that inhibit RNA-modifying enzymes and proteins associated with cancer.
“I like working on the cutting edge of new biology,” Copeland told Xconomy.
The company will use a variety of laboratory techniques, including a CRISPR-based system that, writes Xconomy, “allows them to systematically knock out genes involved in RNA modification one by one, in a wide range of cancer cell types.”
So far Accent has identified approximately 20 targets and has prioritized four. It hopes to identify more.
Copeland launched Epizyme in 2008 as its first chief scientific officer. He was there for nine years, launched an initial public offering, and pushed three drugs into the clinic. Epizyme is also an epigenetics company, focused on drugs that inhibit enzymes that alter DNA. The difference between epigenetics and epitranscriptomic drugs is that epitranscriptomic drug target RNA modifications instead of DNA modifications. The thinking on the part of Copeland and Accent is that the focus on RNA will be more precise.
https://bit.ly/2LzBAdy
Sunday, May 27, 2018
Bloom Science Launches from Exclusive UCLA Tech License
San Diego-based Bloom Science launched to develop epilepsy treatments based on a new class of neuroprotective drugs. The company, whose research was published in the journal Cell today, focuses on gut bacteria involved in the anti-seizure effects of the ketogenic diet.
The ketogenic diet was developed in the 1920s to treat epilepsy. In rare types of epilepsy, and in patients who don’t respond to other therapeutics, the diet has positive effects, but because it is low carbohydrate, high fat, compliance is usually a problem. Until recently, it wasn’t clear why the diet worked.
Elaine Hsiao, assistant professor in the Department of Integrative Biology and Physiology in the Life Sciences Division of the UCLA College, and the UCLA David Geffen School of Medicine,as well as co-founder of Bloom, is the senior author of the article, which shows in two preclinical mouse models that the diet increases the growth of certain but bacteria. These specific strains of bacteria are necessary to offer seizure protection. They regulate circulating metabolites that stimulate neurotransmitters in the brain, specifically gamma aminobutyric acid (GABA).
The company will focus on developing products from these bacteria that modulate GABA.
“Despite the introduction of 20 new anti-epilepsy drugs in recent decades, a third of patients with epilepsy never achieve seizure control, and half of those who respond to treatment report negative side effects that limit compliance and negatively impact their quality of life,” said Anthony Colasin, Bloom’s chief executive officer, in a statement. “New and better approaches to managing epilepsy are urgently needed. At Bloom, we are addressing that need by hacking the ketogenic diet to identify microbes with therapeutic potential, and then leveraging a unique business model to develop those microbes as neuroprotective therapies for orphan epilepsy indications in an accelerated time frame.”
The UCLA Technology Development Group has filed a patent on the technology and exclusively licensed it to Bloom.
Colasin is the co-founder, chief executive officer and director of Bloom. Prior to founding Bloom, he was chief business officer of Bionomics, and before that, vice president of Business Development for Ironwood Pharmaceuticals.
Christopher Reyes is the company’s co-founder, chief scientific officer and director. He is also the co-founder and director of Hove. From September 2012 to December 2015 he was vice president of Research and Development Biologics at Bionomics. Before that he was co-founder, chief scientific officer and director of Eclipse Therapeutics.
Hsiao said in a statement, “The human body is comprised of trillions of resident microbes that are important for normal biology, including brain health. The discovery has the potential to impact the many conditions that are associated with alterations in GABA and shown to be modified by the ketogenic diet, such as epilepsy, Alzheimer’s disease, Parkinson’s disease, autism, anxiety and schizophrenia.”
Bloom will be working in the booming area of microbiome research and development, working to develop drugs that exploit the effects of gut bacteria on various diseases. Other companies working in the area include Synthetic Biologics, Microbiota, Sciota Biosciences, and the University of California San Diego School of Medicine, which is running the American Gut Project, a crowdsourced project focused on the human microbiome.
Kaplan, CBLA Collaborate on 1st Official Occupational English Test Study Guide
Cambridge Boxhill Language Assessment (CBLA), the owners of the Occupational English Test (OET), and Kaplan Test Prep, the world leader in test preparation, today announced a collaboration on publishing “Official Guide to OET”, the first official study guide for the healthcare-specific exam.
OET assesses the English language skills of healthcare professionals seeking to register and practice in an English-speaking environment. Unlike general English tests, OET test materials are based on real healthcare scenarios so employers can be confident that successful candidates have the right level of English to provide safe, high-quality patient care.
OET results are recognized by healthcare boards and councils globally, including in the UK, Ireland, Australia, New Zealand, Singapore and Dubai as proof of English language proficiency.
The book, available by August, will be the first guide to prepare students for the updated OET, which launches in September.
The OET has gained popularity, with double-digit growth annually, as healthcare professionals increasingly look to this exam as most appropriate for assessing their English language ability.
“We are delighted to have worked with Kaplan Test Prep to create the first official OET study guide. The new book is relevant, an excellent study resource, and will no doubt assist our candidates in developing both the English language skills and confidence to deliver patient safety and quality care in a variety of healthcare settings,” said Sujata Stead, CEO of CBLA.
”The collaboration with CBLA to create this official guide allows us to produce a world-class preparation resource that combines Kaplan’s unparalleled expertise in proven test-taking strategies with verified test-like content vetted by CBLA,” said Steven Marietti, President, Licensure division, Kaplan Test Prep.
Med Students Still Do Pelvic Exams on Women Under Anesthesia
Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU School of Medicine. How many of you watching learned to do a pelvic exam in medical school or residency on an anesthetized woman, who was getting ready to undergo a surgical procedure for some sort of obstetrical/gynecologic condition? Many people did. I thought the practice was over. After all, many groups, including the American College of Obstetricians and Gynecologists, have issued statements that that should not happen; no one should be using a woman to learn how to do a pelvic exam without consent before that teaching practice is undertaken.
However, when Phoebe Friesen, a former student of mine, was at NYU, she found out that in other parts of the country, and in other nations, there are still women who are being used as teaching subjects for these exams without their permission, without any consent. The practice is just unethical. It’s wrong. It should not be happening. Pointedly, it is because the women themselves have the right to and deserve the respect of giving their permission. Obviously, it is an intimate bodily contact, and more than one person might be involved in these exams.
Think about people like Larry Nassar, who was convicted of molesting young women by touching them without their permission in the name of a therapeutic intervention. Nassar is an extreme case—I understand that. He was a deviant who was getting sexual pleasure from molesting women in the name of medical practice. Nonetheless, part of the outrage about what he was doing is nonconsensual touching in intimate areas on women. We don’t want to see that practice even extended for the noble reason of trying to learn and teach about pelvic exams. I think we should be asking the women, because they have every right to say yes or no, to say whether it’s okay to do that. Some may say yes, some may say no.
If too many people say no, I think the other option is to pay women or find women who would allow people to examine them. Interestingly enough, you may learn better on a conscious woman than on an unconscious woman. Many schools have moved to the practice of hiring women to take on this particular role to help students learn. The other reason it is very important not to do any type of nonconsensual touching is that it teaches students the wrong message. What we want to be saying is, get consent when you touch somebody. Don’t treat somebody as an object or a thing; get their permission. It’s very important to have informed consent.
Sometimes informed consent is a difficult thing to obtain, but it isn’t in this area. People can understand very well what they are being asked. You want to teach the students to respect their patients when they are going to do something like this. It’s very important to send the right message if you’re going to use a patient in a teaching or research role, and to get their permission.
At the end of the day, this is a practice that should come to an abrupt and immediate halt. There should be no teaching on unconscious women without their permission. It’s a violation of their privacy, their dignity, their right not to be touched without their consent. Continuing the practice sends the absolutely wrong message to medical students about how they should be relating to their patients.
LA’s people walker is beating loneliness, one step at a time
Chuck McCarthy’s walking service provides fresh air, exercise and companionship for $30 an hour—but peeing on trees is an absolute no-no.
The Los Angeles-based entrepreneur works with humans, not animals, and is striking a blow for health and social inclusion as the founder of the famously car-friendly city’s first people-walking business.
“I was thinking about becoming a dog walker. But I’ve never had a dog in the city, so I’ve never had to pick up dog poop,” McCarthy told AFP on a recent leisurely saunter in the Hollywood Hills.
“I was also seeing a lot of personal trainer ads. And so I kind of said to my girlfriend, ‘Maybe I’ll just become a people walker.’”
McCarthy was joking but the more he thought about it, the more he realized there was a need for the kind of comradeship he could provide.
The People Walker started as a one-man operation two years ago. But demand was so high that McCarthy now has a roster of 35 walkers, and a website where people can choose routes and walking partners.
Social disconnection has been linked in various studies to depression, heart disease, diabetes and cancer, and can shorten life as profoundly as regular smoking, according to some estimates.
Eric Klinenberg, a professor of sociology at New York University, identified a major cause of loneliness in a recent column in The New York Times: a growing global culture of individualism.
‘Human connection’
It’s not that people have fewer friends, say experts, but rather that the “gig economy” has produced a generation of freelancers with none of the routines or social bonds that traditionally connected workers.
“I’ve walked people that are married with kids that have tons of friends. It’s about convenience and it’s about location and basically having things your way,” McCarthy says.
Meanwhile smartphones and social media have deepened divisions, replacing real human relationships with the ersatz companionship of a social media following.
Instead of “screaming into the void of Twitter or Facebook,” McCarthy’s clients get to enjoy real human connections with people that don’t know them and won’t judge or gossip.
“It seems like something new but it’s very similar to going to confession, to a bar, to a therapist, or going to a hairstylist,” he tells AFP.
McCarthy is an aspiring actor, which makes him coy about revealing his exact age—”I guess I’m in my 30s,” he concedes—but auditions have taken a back seat to the business recently.
“I still wouldn’t turn down a starring role opposite George Clooney,” he adds, just for the record.
The business is on the cusp of making the kind of money McCarthy could call a living, with an app about to launch and grand plans for expansion across California, the US and, eventually, the world.
All shapes and sizes
McCarthy has no idea how far his feet have taken him in the last two years but he walks clients four or five times a week, typically for an hour, and describes himself as more of a listener than a talker.
“It’s less of a confession and more of a conversation. So I wouldn’t say that I’m getting the deepest darkest secrets and nobody is breaking down crying on our walks,” he says.
McCarthy’s clients come in all shapes and sizes, and walk for a variety of reasons.
Anie Dee, a Wisconsinite in her late 20s who decamped to LA seven years ago, had been driving for a ride share service, sitting down all day, and decided last year to get out more.
“I have some health issues so walking long distances is very difficult for me. And so having somebody with me, we walk a lot further than I ever thought I could,” she told AFP.
The freelance theater box office manager noticed as she began going out with McCarthy that her mood and outlook were noticeably more positive.
“When you’re working a lot of desk jobs and you’re by yourself, you don’t really have that social aspect,” she said.
“So when you go for a long walk it’s like, ‘I feel refreshed—this is really nice.’”.
Aggression neurons identified
High activity in a relatively poorly studied group of brain cells can be linked to aggressive behaviour in mice, a new study from Karolinska Institutet in Sweden shows. Using optogenetic techniques, the researchers were able to control aggression in mice by stimulating or inhibiting these cells. The results, which are published in the scientific journal Nature Neuroscience, contribute to a new understanding of the biological mechanisms behind aggressive behaviour.
Aggression is a behaviour found throughout the animal kingdom that shapes human lives from early schoolyard encounters to armed, global conflict. Like all behaviour, aggression originates in the brain. However, the identity of the neurons involved, and how their properties contribute to the stereotyped expression of interpersonal conflicts, remains largely a mystery. Researchers at Karolinska Institutet now show that a previously relatively unknown group of neurons in the ventral premammillary nucleus (PMv) of the hypothalamus, an evolutionarily well-preserved part of the brain that controls many of our fundamental drives, plays a key role in initiating and organising aggressive behaviour.
Studying male mice, the researchers found that the animals that displayed aggression when a new male was placed in their home cage also had more active PMv neurons. By activating the PMv through optogenetics, whereby neurons are controlled using light, they were able to initiate aggressive behaviour in situations where animals do not normally attack, and by inhibiting the PMv, interrupt an ongoing attack.
The mapping of the PMv neurons also showed that they, in turn, can activate other brain regions such as the reward centres.
“That could explain why mice naturally make their way to a place where they have experienced an aggressive situation,” says the study’s lead author Stefanos Stagkourakis, doctoral student at the Department of Neuroscience, Karolinska Institutet. “We also found that the brief activation of the PMv cells could trigger a protracted outburst, which may explain something we all recognise—how after a quarrel has ended, the feeling of antagonism can persist for a long time.”
Aggression between male mice is often ritualised and focused less on causing harm than on establishing a group hierarchy by determining the strongest member. This can be studied experimentally in the so-called tube test, wherein two mice encounter each other in a narrow corridor, from which observations can be made about submission and dominance. By inhibiting the PMv cells in a dominant male and stimulating the same cells in a submissive male, the researchers were able to invert their mutual hierarchical status.
“One of the most surprising findings in our study was that the role-switch we achieved by manipulating PMv activity during an encounter lasted up to two weeks,” says study leader Christian Broberger, associate professor at the Department of Neuroscience, Karolinska Institutet.
The researchers hope that the results can contribute to new strategies for managing aggression.
“Aggressive behaviour and violence cause injury and lasting mental trauma for many people, with costly structural and economic consequences for society,” says Dr. Broberger. “Our study adds fundamental biological knowledge about its origins.”
Explore further: Unexpected discovery gives new model for studying brain networks
More information: Stefanos Stagkourakis et al, A neural network for intermale aggression to establish social hierarchy, Nature Neuroscience (2018). DOI: 10.1038/s41593-018-0153-x
VA turns to foster care for veterans instead of putting them in nursing homes
Ralph Stepney’s home on a quiet street in north Baltimore has a welcoming front porch and large rooms, with plenty of space for his comfortable recliner and vast collection of action movies. The house is owned by Joann West, a licensed caregiver who shares it with Stepney and his fellow Vietnam War veteran Frank Hundt.
“There is no place that I’d rather be. . . . I love the quiet of living here, the help we get. I thank the Lord every year that I am here,” Stepney, 73, said.
It’s a far cry from a decade ago, when Stepney was homeless and “didn’t care about anything.” His diabetes went unchecked and he had suffered a stroke — a medical event that landed him at the Baltimore Veterans Affairs Medical Center.
After having part of his foot amputated, Stepney moved into long-term nursing home care at a Department of Veterans Affairs medical facility, where he thought he’d remain — until he became a candidate for a small VA effort that puts aging veterans in private homes: the Medical Foster Homeprogram.
The $20.7 million-per-year program provides housing and care for more than 1,000 veterans in 42 states and Puerto Rico, serving as an alternative to nursing home care for those who cannot live safely on their own. Veterans pay their caregivers $1,500 to $3,000 a month, depending on location, saving the government about $10,000 a month in nursing home care. It has been difficult to scale up, though, because VA accepts only foster homes that meet strict qualifications.
For the veterans, it’s a chance to live in a home setting with caregivers who treat them like family. For VA, the program provides an option for meeting its legal obligation to care for ailing, aging patients at significantly reduced costs, because the veterans pay room and board directly to their caregivers.
Cost-effectiveness is but one of the program’s benefits. Stepney and Hundt, 67, are in good hands with West, who previously ran a home health-care services company. And they’re in good company, watching television together in the main living room, going twice a week to a center that offers daytime care and sitting on West’s porch chatting with neighbors.
West, who considers caring for older adults “her calling,” also savors the companionship and finds satisfaction in giving back to those who spent their young lives in military service to the United States.
“I took care of my mother when she got cancer and I found that I really had a passion for it. I took classes and ran an in-home nursing care business for years. But my dream was always to get my own place and do what I am doing now,” West said. “God worked it out.”
The Medical Foster Home program has slightly more than 700 licensed caregivers who live full time with no more than three veterans and provide round-the-clock supervision and care, according to VA. Akin to a community residential care facility, each foster home must be state-licensed as an assisted-living facility and submit to frequent inspections by VA as well as state inspectors, nutritionists, pharmacists and nurses.
Unlike typical community care facilities, foster home caregivers are required to live on-site and tend to the needs of their patients themselves 24/7 — or supply relief staff.
“It’s a lot of work, but I have support,” West said. “I try to make all my personal appointments on days when Mr. Ralph and Mr. Frank are out, but if I can’t, someone comes in to be here when I’m gone.”
VA medical foster home providers also must pass a federal background check, complete 80 hours of training before they can accept patients, plus 20 hours of additional training each year, and allow VA to make announced and unannounced home visits. They cannot work outside the home and must maintain certification in first aid, CPR and medicine administration.
But one prerequisite cannot be taught — the ability to make a veteran feel at home. West has grown children serving in the military and takes pride in contributing to the well-being of veterans.
“It’s a lot of joy taking care of them,” she said of Stepney and Hundt. “They deserve it.”
To be considered for the program, veterans must be enrolled in VA health care; have a serious, chronic disabling medical condition that requires a nursing home level of care; and need care coordination and access to VA services. It can take up to a month to place a veteran in a home once they are found eligible, according to VA.
The veterans also must be able to cover their costs. Because medical foster homes are not considered institutional care, VA is not allowed to pay for it directly. The average monthly fee, according to VA, is $2,300, which most veterans cover with their VA compensation, Social Security and savings, said Nicole Trimble, Medical Foster Home coordinator at the Perry Point VA Medical Center in Maryland.
Pilot program takes off
Since 1999, the Department of Veterans Affairs has been required to provide nursing home services to veterans who qualify for VA health care and have a service-connected disability rating of 70 percent or higher, or are considered unemployable and have a disability rating of 60 percent or higher.
VA provides this care through short- or long-term nursing home facilities, respite care, community living centers on VA hospital grounds, private assisted living facilities and state veterans homes.
Shortly after, the VA Medical Center in Little Rock launched an alternative — a pilot program that placed veterans in individual homes, at an average cost to VA of about $60 a day, including administration and health-care expenses, compared with upward of $500 a day for nursing home care.
And because veterans who are enrolled in the Medical Foster Care program must use VA’s Home Based Primary Care program, which provides an interdisciplinary team of health professionals for in-home medical treatment, the program saves VA even more. One study showed that the home-based care has yielded a 59 percent drop in VA hospital inpatient days and a 31 percent reduction in admissions among those who participate.
More than 120 VA medical centers now oversee a Medical Foster Home program in their regions, and VA has actively promoted the program within its health system.
It also has attracted bipartisan congressional support. In 2013, Sen. Bernie Sanders (I-Vt.) introduced a bill to allow VA to pay for medical foster homes directly.
In 2015, former House Veterans’ Affairs Committee chairman Rep. Jeff Miller (R-Fla.) introduced similar legislation that would have allowed VA to pay for up to 900 veterans under the program.
And this month , Rep. Clay Higgins (R-La.) raised the issue again, sponsoring a bill similar to Miller’s. “Allowing veterans to exercise greater flexibility over their benefits ensures that their individual needs are best met,” Higgins said in support of the program.
A guardian ‘angel’
Foster care has been a blessing for the family of Hundt, who suffered a stroke shortly after his wife died and was unable to care for himself. Hundt’s daughter, Kimberly Malczewski, lives nearby and often stops in to visit her dad, sometimes with her 2-year-old son.
“I’m not sure where my father would be if he didn’t have this,” she said. “With my life situation — my husband and I both work full time, we have no extra room in our house, and we have a small child — I can’t take care of him the way Miss Joann does.”
Trimble, whose program started in 2012 and has five homes, said she hopes to expand by two to three homes a year. VA will remain meticulous about selecting homes.
“There is a strict inspection and vetting process to be a medical foster home,” Trimble said. “We only will accept the best.”
It also takes a special person to be an “angel,” as the caregivers are referred to in the program’s motto, “Where Heroes Meet Angels.”
Stepney and Hundt agree West has earned her wings. On a recent cruise to Bermuda, she brought Stepney and Hundt along.
For Hundt, it was the first time he’d been on a boat. And Stepney said it was nothing like the transport ships he and his fellow troops used in the late 1960s: “Well, I’ve gotten to travel, but it was mainly two years in Vietnam, and there weren’t any women around.”
When asked why she brought the pair along, West said caregiving is “a ministry, something you really have to like to do.”
“And you know how the saying goes,” she said. “When you like what you do, you never work a day in your life.”
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