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. Full story »
This post is the first in a two-part series on clinical trials in autism spectrum disorders. Read part 2.
In the world of neurodevelopmental disorders, an exciting trend is the emergence of specific molecular targets and treatments through genetic research. A case in point is IGF-1 therapy for Rett syndrome, a devastating disorder in girls that affects their ability to speak, walk, eat and breathe. It causes autism-like behaviors, intellectual disability and repetitive hand-wringing movements—a hallmark of the disorder.
A Phase I trial, published this week in the Proceedings of the National Academy of Sciences Early Edition, has modest but consistent results suggesting improvements in some salient features of the disorder.
Current treatments for Rett syndrome address only the symptoms and comorbidities, such as seizures, anxiety and scoliosis, but not the disease itself. But in 2007, findings in a mouse model (which even replicated the hand-wringing) changed how scientists think about Rett and other neurodevelopmental disorders, previously thought to be untreatable. Full story »
A project that set out to build better shunts ended with potential ways to help kids avoid shunts altogether.
Shunts often are surgically placed in the brains of infants with hydrocephalus to drain excess cerebrospinal fluid. Unfortunately, these devices eventually fail, and the problem is hard to detect until the child shows neurologic symptoms. CT and MRI scans may then be performed to check for a blockage of flow—followed by urgent neurosurgery if the shunt has failed.
Early detection of shunt failure was the problem pitched last fall at Hacking Pediatrics in Boston. Two bioengineers, Christopher Lee, a PhD student at Harvard-MIT Health Sciences and Technology program, and Babak Movassaghi, PhD, an MBA candidate at MIT Sloan, took the bait.
“We heard that parents would not take vacations in areas without an experienced neurosurgeon around,” says Movassaghi, a former Philips Healthcare engineer with 32 patents in cardiology and electrophysiology. “We were intrigued to solve that.” Full story »
Good things, including therapeutics, can come in small packages—and increasingly this means nano-sized packages. For a sense of the scale of these diminutive tools, a strand of human DNA is 2.5 nanometers in diameter.
Nanomedicine offers the promise of drugs that are activated by physiologic stimuli in the body (like the shear stress of blood flow that’s partially blocked by a clot), that can home to very specific targets in the body (like pancreatic islets that are being attacked by the immune system in diabetes) and that carry their own imaging agents—a built-in “metric” to show that they’re working. Biomaterials are being crafted to enhance their properties—like adding gold “nanowires” to heart patches to increase their electrical conductivity.
Vector’s new sister publication, Innovation Insider, looks at the promise and challenges of nanomedicine—both technical and regulatory. Read more about nanoscissors, theranostics, quantum dots and how the future is nano.
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Some believe that ACA's insurance exchanges leave gaps in pediatric protection.
Funding for the federal Children’s Health Insurance Program (CHIP)
will run out in 2015. Will this leave many kids without health insurance?
About 8 million children currently receive health insurance through CHIP, created in 1997 to bring coverage to children whose families earn too much to qualify for Medicaid but not enough to buy private insurance. States administer the program and receive federal matching funds to cover costs. In 2009, Congress reauthorized funding for CHIP through 2015.
What will happen to CHIP beyond 2015 is uncertain, not just because of the funding deadline but also because of changes brought on by the 2010 Affordable Care Act (ACA). Many believe that the ACA’s Medicaid enrollment incentives and expanded tax credits will add so many lower-income kids to the insurance rolls that CHIP will become unnecessary and simply go away. Others, however, say that the plans sold through the ACA’s insurance exchanges could produce gaps in coverage for children, making it crucial to keep CHIP funded. Full story »
Maitreyi Mazumdar, MD, MPH, practices pediatric neurology at Boston Children’s Hospital. She leads a research program in Bangladesh that studies the effects of the epidemic of arsenic poisoning on neurological outcomes in children.
Neurodevelopmental disorders, including autism and attention deficit/hyperactivity disorder (ADHD), affect many millions of children and appear to be increasing in frequency worldwide. Improved diagnosis and changes in diagnostic criteria explain a portion of the rise, but not all. In other words, the increase in neurodevelopmental disorders seems to be “real.”
To date, research has mainly invested in finding genetic causes, implicating biological pathways that affect, for example, the formation of synapses and the production of neurotransmitters. Such discoveries improve our understanding of the basic biology of neurodevelopmental disorders and may ultimately lead to new therapies. But genetic variants alone cannot explain the recent rise; if they did, population rates of neurodevelopmental disorders would be expected to stay the same, or even decrease over a 30- to 40-year period, due to affected people likely having fewer children. Instead, reported rates have steadily increased over the past several decades. Something else is going on. Full story »
The people who deliver care are starting to think in terms of population health.
A growing number of health care professionals are looking at their patients not just as individuals with unique concerns but also as members of larger groups with common problems and needs. This broader, population-based framework could lead to better health outcomes for more people, according to Jonathan Finkelstein, MD, MPH
of Boston Children’s Hospital.
“The health care system is changing from one that’s more reactive to illness—you come see the doctor when you’re not well—to one that’s more responsible for the promotion of health for defined groups of people,” he explains. While individual patients will always be treated as, well, individuals, the concept of population health can help providers “figure out the most appropriate services within a set of limited resources for specific groups.” Full story »
Ondansetron has not decreased IV rehydration as originally intended.
Acute gastroenteritis is one of the leading causes of emergency department (ED) visits for children, accounting for more than 1.7 million trips each year. Its standard treatment has traditionally been rehydration by giving fluids orally or intravenously. Though both methods are equally effective, oral rehydration is preferred as it results in less discomfort and helps stop diarrhea sooner. The IV route is often employed in children who are vomiting and unable or unwilling to drink a large amount of liquids.
About a decade ago, ED physicians began orally administering the anti-nausea medication ondansetron to vomiting patients with gastroenteritis who were unable to hold down oral fluids. Once the ondansetron has stemmed their nausea, children have a much easier time with oral rehydration.
However, the lack of standardized use of this drug has led to its overuse. Though intended to reduce the use of IV rehydration, ondansetron proved so effective at reducing vomiting that its use skyrocketed in the course of just a few years. Full story »
Israel Green-Hopkins, MD, is a second-year fellow in Pediatric Emergency Medicine at Boston Children’s Hospital and a fierce advocate for innovation in health information technology, with a passion for design, mobile health, remote monitoring and more. Follow him on Twitter @israel_md.
A few months ago, I spent 15 minutes filling out a detailed health data form at the doctor’s office. The paper form contained multiple questions about my health, family history, medications and basic demographic information. I assumed that an administrative specialist would code it into the practice’s electronic medical record (EMR) to be put to use. So it came as a surprise when I spent another 5 minutes reviewing the form with my physician, who then proceeded to type this information into the EMR herself. I’m confident neither my physician nor I felt enabled by the experience.
Countless people have had a similar experience—or worse, filled out a form with no sign that any clinician ever saw the information. Though the industry has made outstanding progress in adopting EMRs, the practice of data acquisition from patients remains cloudy. Patient-generated health data (PGHD), a term encompassing all forms of data that patients provide on their own, is a relatively new concept in health care. It falls into two broad groups: historical data and biometric data. Full story »
The Sylvian fissure (via BodyParts3D/Wikimedia Commons)
Five people with an unusual pattern of brain folds have afforded a glimpse into how the human brain may have evolved its language capabilities.
How the human brain develops its hills and valleys—expanding its surface area and computational capacity—has been difficult to study. Mice, the staple of scientific research, lack folds in their brains.
Christopher Walsh, MD, PhD, head of the Division of Genetics and Genomics at Boston Children’s Hospital, runs a brain development and genetics clinic and has spent 25 years studying people in whom the brain formation process goes awry. Some brains are too small (microcephaly). Some have folds, or gyri, that are too broad and thick (pachygyria). Some are smooth, lacking folds altogether (lissencephaly). And some have an abnormally large number of small, thin folds—known as polymicrogyria.
In 2005, studying people with polymicrogyria, Walsh and colleagues identified a mutation in a gene known as GPR56, a clue that this gene helps drive the formation of folds in the cortex of the human brain.
In a study published in today’s issue of Science, Walsh and his colleagues focused on five people whose brain MRIs showed polymicrogyria, but just in one location—near a large, deep furrow known as the Sylvian fissure, which includes the brain’s primary language area. Full story »