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In a small pilot study funded by Autism Speaks, treatment with folinic acid – a naturally occurring form of folate – improved communication and eased autism symptoms in language-impaired children who have autism. The gains were greatest in a subgroup of children who tested positive for an autoantibody that may partially block this vitamin from entering brain cells.
Folinic acid is a more metabolically active form of folate (also known as B9) than is folic acid, the synthetic form of folate found in many prenatal and children’s vitamins.
“Though caution is needed with any small study, we hope these results will lead to the kind of large trial needed to fully validate a promising experimental treatment for a subset of individuals with autism,” comments Autism Speaks Interim Chief Science Officer Mathew Pletcher. “If confirmed by further research, this would exemplify the promise of personalizing treatments for autism’s many causes and subtypes.”
In the study, the researchers randomly selected 48 nonverbal or minimally verbal children with autism (average age 7 years) to take either two daily doses of folinic acid (up to 50 mg per day depending on body weight) or a look-alike dummy pill. Folinic acid occurs naturally in many foods (lentils, liver and many green vegetables), but at much lower levels.
Neither the researchers, the children nor their families knew who received the actual treatment (23 children) and who received the placebo (25 children) until after the 12-week trial concluded. Before and after the trial, the researchers administered standardized tests to measure verbal communication and behavioral symptoms of autism.
As a group, the children who took the folinic acid showed greater improvements in both verbal communication and behavioral symptom severity. However, the improvements were significantly greater among a subset of ten children in the folinic acid group who tested positive for an autoantibody. According to the researchers' theory, the antibody may interfere with the transport of the nutrient into brain cells.
The researchers propose that high doses of folinic acid helped improve brain function by overcoming this blockade and restoring normal folate levels inside brain cells. The theory is based on previous research by the group, which detected this folate-blocking autoantibody in 60 percent of children who have autism, but just 3 percent of children with developmental delays that do not involve autism.
The findings are also in line with a large body of research, by other scientists, showing that women who take prenatal vitamins containing folate have a lower risk of having children affected by autism.
“These observations suggest that identifying autism and the presence of folate receptor autoantibodies early in life may present an opportunity to prevent at least some of autism’s developmental deficits with folinic acid treatment,” says senior researcher Edward Quadros, of the State University of New York Downstate Medical Center. Before such treatment can be recommended, larger studies are needed to confirm safety and effectiveness.
The federal Interagency Autism Coordinating Committee (IACC) invites the autism community to participate in its next quarterly meeting – Wednesday, October 26, from 9 to 5 Eastern, at the National Institutes of Health, in Bethesda, Maryland. The meeting will also be available via live webcast.
Join remotely by live webcast or conference call here.
Under the mandate of the Autism CARES Act, the IACC coordinates all autism research and service activities within the US Department of Health and Human Services. It is charged with ensuring that a wide range of ideas and perspectives are considered and discussed in a public forum.
Interested in presenting comments at the July meeting or sending written comments on an issue important to you? Send them to email@example.com. The deadline to register to give in-person comments is 5 pm ET October 12, with submission of a written copy of remarks by 5 pm ET October 18. Submission of written comments for distribution to IACC members is likewise 5 pm ET October 18.
For more information, also visit the IACC Events page.
Free monthly webinars on autism research and healthcare
Sponsored by the Autism Speaks Autism Treatment Network & the Autism Intervention Research Network on Physical Health
“Advances in Autism Research & Care” is a monthly webinar series sponsored by the Autism Speaks Autism Treatment Network as part of its federally funded role as the nation’s Autism Intervention Research on Physical Health. In focus, the webinars alternate between research reports by ATN/AIR-P investigators and trending topics in autism healthcare.
Though focused on educating healthcare providers, the webinars are open to the public. Members of the autism community are particularly welcome.
Research webinars feature current AIR-P research study investigators, while care focused themes cover hot topics in the field of autism, and promote idea generation for future research.
Upcoming webinars for 2016 include:
Tuesday, Nov. 15 from 2-3 pm ET: Neonatologist Bryan Burke, of the University of Arkansas for Medical Sciences, discussing autism spectrum disorders and telehealth. Register for the webinar here.
Thursday, Dec. 1 from 1:30-2:30 pm ET: Psychologist Jayne Bellando, of Arkansas Children’s Hospital, and Angeletta Giles, a member of the hospital’s ATN Family Advisory Committee, will discuss ways to reach underserved, rural populations. Register for this webinar here.
Contact Audrey Wolfe for more information about this webinar series.
We’re pleased to announce the next free webinar in our ongoing series on the environmental epigenetics of autism – co-sponsored by the Escher Fund for Autism, Autism Speaks and the Autism Science Foundation.
On Tuesday, November 15, from 1 pm Eastern, please join us for:
Presented by neuroscientist Tracy Bale, of the Perelman School of Medicine at the University of Pennsylvania, with an introduction by neurodevelopmental neuroscientist Donna Werling, of the University of California-San Francisco. Register here.
Autism BrainNet is dedicated to advancing the highest quality research on autism through the generous post-mortem donation of brain tissue from families affected by the disorder. To learn more about the program – including information about registering your family – click here.
In this month’s Autism Matters podcast, host Laura Crane interviews Autism Speaks-funded researcher Helen Tager-Flusberg about innovative ways to include nonverbal and minimally verbal children and adults in autism research.
“In part [this is] because of the challenging behaviors they present alongside their very limited means for communication,” Dr. Tager-Flusberg writes in this month’s issue of Autism.
In the podcast and its related article, Dr. Tager-Flusberg discusses some of the methods she has successfully used to include this often-neglected group in her studies. She also discusses some of the advances in understanding autism that have resulted from involving those who have little or no language.
Also see “Autism Speaks (and signs)”
In a small new study, a commonly used diabetes drug curbed the troublesome weight gain that is a common side effect of the only two medicines approved for reducing agitation in children and teens with autism.
The promising results of the study – which took place at four centers in the Autism Speaks Autism Treatment Network (ATN) – appear in the latest issue of JAMA Psychiatry. The research was made possible by the ATN’s federally funded role as the nation’s Autism Intervention Research Network for Physical Health.
Risperidone (brand name Risperdal) and aripiprazole (Abilify) are the only medicines approved by the U.S. Food and Drug Administration for reducing agitation and irritability in children with autism spectrum disorder (ASD). These medicines become important when serious agitation – including aggression – does not respond to non-drug, behavioral therapy. However, both risperidone and aripiprazole commonly produce significant weight gain – a worrisome side effect given obesity’s many associated health risks.
Controlling a serious side effect of autism medications
"It's critically important that we investigate new ways to support healthy outcomes as early as possible for those who are on these medications," says pediatric neurologist Evdokia Anagnostou, the study’s principal investigator and co-director of the Autism Speaks ATN at Toronto’s Holland Bloorview Kids Rehabilitation Hospital. "Use of antipsychotics to help manage irritability associated with ASD can sometimes be long-term, which means we need to provide families with solutions that support lasting optimal health in their children," she emphasizes.
Over the course of 16 weeks, the researchers tracked changes in body mass and performed blood work on 60 study participants, ages 6 to 17. Twenty-eight of the children and teens took the diabetes drug metformin in addition to their usual dose of risperidone or aripiprazole. The rest took an inactive placebo pill along with their behavioral medicines. Neither the researchers nor the participating families knew who received the metformin and who received the dummy treatment until the end of the study.
A clear difference in weight control
As a group, those taking the placebo continued to gain weight over the course of the trial. By contrast, the group taking metformin saw an overall reduction in weight. Most remarkably, three participants taking metformin experienced an 8 to 9 percent decrease in body mass. The researchers saw no changes in obesity-associated metabolic measures such as insulin sensitivity and cholesterol. The 16-week study period may not have been long enough to detect such health benefits, they write.
Overall, the metformin was “well-tolerated,” the researchers report. However, as a group, those taking metformin had more days of gastrointestinal issues such as constipation and diarrhea than did those taking the placebo. (This side effect was not associated with individual weight loss.) In addition, the researchers discontinued metformin in five children because of increased agitation or sedation that may or may not have been caused by the drug.
Given the promising results of this small pilot study, the researchers call for follow-up studies enrolling more children for longer periods.
“Medications such as risperidone and aripiprazole are appropriate only for severe behavioral problems when non-drug approaches have not been adequate,” adds developmental pediatrician Paul Wang, Autism Speaks’ head of medical research. “It’s good to know that metformin has the potential to help manage the weight gain that often accompanies these medications.” (Dr. Wang was not directly involved in the study.)
The Autism Speaks ATN centers participating in the study included the Holland Bloorview Kids Rehabilitation Hospital, in Toronto; Ohio State University Wexner Medical Center and Nationwide Children’s Hospital, in Columbus; the University of Pittsburgh; and Vanderbilt University, in Nashville.
For more on this study, see the video below, courtesy The Ohio State University Wexner Medical Center.
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