For patients with celiac disease, following a gluten-free diet is complicated and often challenging.
“Our patients are navigating a gluten-free diet without any feedback to guide them,” says Jocelyn Silvester, MD, PhD, director of research at the Celiac Disease Program at Boston Children’s Hospital. “Symptoms are not a reliable indicator of gluten exposure. Many patients may not have any symptoms at all.”
For clinicians, assessing how well patients are doing on a gluten-free diet can be equally difficult. “There are no good measures of how well the gluten-free-diet is working or how well patients are following the diet,” Silvester says.
Moreover, tolerance to gluten can vary in celiac disease. Some children have symptoms despite being (apparently) on a gluten-free diet. Others have no symptoms after a gluten exposure, yet show severe atrophy of the nutrient-absorbing villi on intestinal biopsy. Villous atrophy poses a risk for complications, such as poor growth, anemia and osteoporosis. …
Sepsis, or blood poisoning, occurs when the body’s response to infection damages its own tissues, leading to organ failure. It is the most common cause of death in people who have been hospitalized, yet no new therapies have been developed in the last 30 years. Many treatments that have prevented death in animal experiments have failed in clinical trials, indicating that a more clinically-relevant sepsis model is needed for therapeutic development.
To bridge this gap, a team of scientists from the Wyss Institute at Harvard University and Boston Children’s Hospital think a better experimental model of sepsis in pigs could help weed out the therapies most likely to succeed in humans. Their method, a scoring criteria to evaluate sepsis in pigs that closely mirrors standard human clinical assessment, is reported in Advances in Critical Care Medicine.…
Boys born with X-linked myotubular myopathy (XLMTM) face a grim prognosis. Extreme muscle weakness leaves many ventilator-dependent from birth, and most infants need feeding tubes. About half pass away before 18 months of age.
Last week, the biotechnology company Audentes Therapeutics announced the dosing of the first patient in a gene-therapy clinical trial — 21 years after the MTM1 gene was first cloned.
Hopes are high. Gene therapy has already shown striking benefits in dogs with XLMTM in studies co-authored by Alan Beggs, PhD, director of the Manton Center for Orphan Disease Research at Boston Children’s Hospital, and colleagues at Généthon and the University of Washington. In the most recent study, 10-week-old Labrador retrievers already showing signs of the disease showed improvements in breathing, limb strength and walking gait after a single dose of the gene therapy vector. …
About 1 out of 100 babies are born with a congenital heart defects. Thanks to medical and surgical advances, these children usually survive into adulthood, but they are often left with developmental, behavioral or learning challenges.
Children with “single-ventricle” defects — in which one of the heart’s two pumping chambers is too small or weak to function properly — are especially at risk for neurodevelopmental problems. “Single-ventricle physiology creates cerebrovascular hemodynamics that can reduce oxygen delivery to the brain,” explains Jane Newburger, MD, MPH, director of the Cardiac Neurodevelopmental Program at Boston Children’s Hospital.
How does this play out in adolescence? In three recent studies, Boston Children’s Heart Center collaborated with the departments of Neurology and Psychiatry to track neurodevelopmental outcomes after corrective Fontan operations. They evaluated preteens and teens as old as 19 — the longest follow-up to date. …
“Our findings may speak to how commonplace discontinuation and non-publication are in medical research in general,” says Natalie Pica, MD, PhD, a senior resident at Boston Children’s Hospital and the study’s coauthor. “We need to make sure that when children participate in clinical trials, their efforts are contributing to broader scientific knowledge.” …
Worldwide, asthma affects an estimated 300 million people, and is expected to surpass 400 million by 2025, according to the World Health Organization. About 1 in 10 U.S. children have asthma, and research shows that the vast majority of them also have allergy. Could that provide a clue to its prevention?
Starting at 2 to 3 years of age, susceptible children start to become sensitized to pollens, mold spores and other airborne allergens. They begin to produce IgE antibodies, which not only trigger allergic reactions but also impair their anti-viral immune responses — potentially leading to more viral infections that can further hasten their progression to asthma.
There’s a natural tension between wanting the FDA to ensure safety and efficacy before a drug enters the market and wanting to speed up what many view as a glacially slow approval process. The rare disease community tends to fall in the second camp, and has become increasingly vocal in calling for more clinical trials, more flexibility in their design and redefinition of what constitutes a benefit.
ALS advocates, for example, have called for a parallel track, “in which FDA provides an early approval based on limited data, and then continues the learning process in a confirmatory clinical trial and if needed, patient registries to collect additional data from patients receiving the drug outside the clinical trial…”
Recent legislation is encouraging patient engagement in drug development, especially for conditions with profound unmet medical needs. In its 2012 iteration, the Prescription Drug User Fees Act (PDUFA) introduced public meetings to get input from the patient community, captured in a series of informative white papers. …
A study last week in The New England Journal of Medicine suggests that exposing infants to peanuts can provide lasting protection against peanut allergy. But what about peanut-allergic children right now? They and their parents live a life of precautions — from pre-screening birthday party menus to segregation at the school lunch table — to avoid life-threatening consumption of even trace amounts of peanut.
Now, a multicenter study reports on a protocol combining the allergy medication omalizumab (Xolair) with controlled, gradually increasing peanut consumption. After 20 weeks, most initially allergic children could safely consume the equivalent of 8 to 10 peanuts at a time. Three months after stopping the medication, most had worked up to 16 to 20 peanuts. …
Ed Anderson, CCRP, is a clinical research specialist for the Clinical Research Center’s Development and Operations Core at Boston Children’s Hospital.
There’s no way around it. Obtaining approval to market a new drug is lengthy, complex, costly and fraught with uncertainty and risk. Financial engineers at MIT propose a strategy to minimize that risk—one that deserves a close look.
In the last 10 years, the aggregate cost of pharmaceutical research and development has doubled, but the number of approved products has remained the same. To compound the problem, a $1.6 billion reduction in NIH funding, caused by the 2013 sequester, has stalled research projects at more than 2,500 research institutions supported by grants. Pressure from investors and stakeholders is pushing pharmaceutical companies to focus on projects with a greater chance of financial success.
As a result, translational studies—those that bridge the gap between basic research and clinical trials—continue to be neglected and account for less than 12 percent of total research funding. …
Walter Kaufmann, MD, is co-director of the Fragile X Syndrome Program and a member of the department of Neurology at Boston Children’s Hospital. He was site principal investigator for three arbaclofen trials sponsored by Seaside Therapeutics and currently advises the company on data analyses. This post is second in a two-part series on clinical trials in autism spectrum disorders. (Read part 1)
The outcomes of drug trials in autism spectrum disorder (ASD) have, to date, been mixed. While atypical neuroleptic drugs have been effective for treating disruptive behavior in people with autism and are FDA-approved for that purpose, no available psychotropic drug has improved the core symptoms of ASD, such as social interaction deficits or stereotypic behaviors.
The heterogeneity—diversity—of ASD in both causes and symptoms may explain treatment failures to some extent. However, we have also lacked drugs targeting the brain mechanisms that underlie ASD. For this reason, targeted trials in fragile X syndrome, informed by neurobiology, have raised hopes of finally addressing core autistic symptoms.