Stories about: clinical trials

New hope for X-linked myotubular myopathy as gene therapy clinical trial begins

gene therapy myotubular myopathy

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.

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Can we improve neuropsychiatric outcomes in children with congenital heart disease?

Jane Newburger studies neurodevelopment in children with congenital heart defects
Jane Newburger, MD, has dedicated her career to helping children with heart defects reach their full potential.

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.

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More clinical trials in kids? Nearly half are unfinished or unpublished

pediatric trials clinical trials
Of 559 interventional trials in children, 19 percent were stopped early and 30 percent of completed trials remained unpublished several years later, finds a new study. (Vmenkov/Wikimedia Commons)

Recent laws like the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act are encouraging clinical trials in children. Yet, as with adult trials, these trials commonly stall out or, if completed, remain unpublished several years later, finds a study published online today in Pediatrics.

“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.”

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Can asthma be nipped in the bud?

asthma
A multicenter randomized trial is testing omalizumab (Xolair) in wheezy toddlers. (FDA/Wikimedia Commons)

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.

A multicenter clinical trial, led by Wanda Phipatanakul, MD, MS, of the Division of Allergy & Immunology at Boston Children’s Hospital, now aims to test whether the anti-IgE drug omalizumab (Xolair) can short-circuit this process.

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Citizen science: Giving patients a voice in drug development

citizen science patient voice drug development

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.

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20-week treatment makes life safer for kids with peanut allergy

peanut allergy

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.

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De-risking drug development: Funding science with financial engineering

401k drug financing
A new proposal suggests spreading drug development risk among many small investors.
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.

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Autism clinical trials are ripe for improvement

Did arbaclofen really fail in autism and fragile X?
Did arbaclofen really fail in autism and fragile X?

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.

Fragile X syndrome is a genetic disorder in which ASD occurs in 15 to 40 percent of cases. Initial results from a Phase 2 trial using the GABA-B agonist arbaclofen demonstrated relatively selective improvements in social avoidance in a wide age-range sample of subjects.

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Pathway(s) to a transparent future for clinical trial data

Medicine on a keyboard - clinical trial data.Ed. note: This is the second in a two-part series on making clinical trial data more transparent. Click here for part 1.

To grossly oversimplify, there are two kinds of people in the world: those who want to see data from clinical trials made widely and freely available, and those who would rather have the data restricted for privacy or business reasons. And as we noted in our last post, there are valid arguments to be made on both sides.

But is there a way to balance the benefits of openness and the safety of confidentiality?

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Raising the veil on clinical trial data

clinical_trial_data_shutterstock_171501788Ed. note: This is the first in a two- part series on making clinical trial data more transparent. Click here for part 2.

2013 was the year when big data became, well, big. Everyone from investment companies to public utilities to security agencies—including medical researchers—are now clamoring for as much data on as many subjects and topics as they can get their digital hands on.

But while data in other fields are becoming ever more open, clinical trial data—especially from corporate-sponsored trials—are relatively hard for medical researchers to obtain.

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