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Nancy Fliesler

Macrophage therapy IBD

Giving patients the right kind of immune cells could curb their IBD, research suggests.

Inflammatory bowel disease (IBD) is miserable for anyone, but when it strikes a child under age 5, it’s much more severe, usually causing bloody diarrhea, wrenching abdominal pain and stunted growth. Early-onset IBD is rare, but on the rise: For reasons unknown, its incidence is increasing by about 5 percent per year in some parts of the world.

A recently identified form of early-onset IBD shows up within months of birth, causing severe inflammation in the large intestine and abscesses around the anus. Recently linked to genetic mutations in the cellular receptor for a signaling protein, interleukin-10 (IL-10), it can also lead to lymphoma later in life.

As with all early-onset IBD, IL-10-receptor deficiency has no good treatment. A bone marrow transplant is actually curative, but carries many risks, especially in infants.

“We’ve been trying to understand why IBD in these children is so severe and presents so early,” says Dror Shouval, MD, a pediatric gastroenterologist at Boston Children’s Hospital and a fellow in the lab of Scott Snapper, MD, PhD. The beginnings of such an understanding—detailed recently in the journal Immunity—could lead to a new treatment approach for this and perhaps other kinds of early-onset IBD. Full story »

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Preliminary findings suggest steroid treatment could improve language and behavior in children with ASD.

Preliminary findings suggest that steroid treatment could improve language and behavior in children with regressive ASD.

In as many as a third of cases of autism spectrum disorder (ASD), children’s language and social skills develop normally at first. Then, between 1 and 2 ½ years of age, they begin to regress, losing words and retreating from interactions with parents—often abruptly. There has been some anecdotal evidence that steroid treatment can help these children, and a small retrospective study agrees—finding improved language and behavior and reversal of a characteristic abnormality in the language processing area of their brains.

Researchers led by Frank H. Duffy, MD, of the Epilepsy Center at Boston Children’s Hospital, looked back at 20 children 3 to 5 years old with documented regressive ASD who had received steroid therapy (prednisolone) under a neurologist’s supervision, generally starting several months after their regression was noted. For comparison, the team also reviewed data from 24 similar autistic children who did not receive steroids. Full story »

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ICISS screengrab2What happens when you try to scale up a successful quality initiative? Eric Fleegler, MD, MPH, and Eugenia Chan, MD, MPH, are facing that challenge with ICISS, their web-based system that went quickly from ideation to adoption by 3,000 patients with attention deficit hyperactivity disorder (ADHD) and their families.

ICISS enables parents, teachers and patients to give online updates on medications, symptoms and school performance in close to real time, then packages that data for clinicians in a visual, actionable fashion. But tasked with introducing ICISS into four other clinics at Boston Children’s Hospital—autism, asthma, depression and epilepsy—a raft of practical, legal and philosophical questions came up about how to handle these patient-generated health data. For example:

  • How should we inform families that they need to contact their provider directly with immediate concerns?
  • What if a parent indicates that a child is at risk of self-harm, and how can we manage this in a timely manner?
  • How can clinics afford to hire additional staff to screen and manage alerts from ICISS when this activity is non-reimbursable?
  • What is the obligation of the provider if actionable data show up months in advance of the scheduled visit?

Fleegler and Chan discuss the challenges and lessons learned in our sister publication, Innovation Insider. We’d be interested to hear from others facing similar questions in handling patient-generated health data.

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A cocktail of approaches is most likely to successfully preserve muscle.

Rather than a single drug, cocktail of approaches is most likely to successfully preserve muscle.

It’s been 28 years since a missing dystrophin protein was found to be the cause of Duchenne muscular dystrophy (DMD), a disease affecting mostly boys in which muscle progressively deteriorates. Dystrophin helps maintain the structure of muscle cells; without it, muscles weaken and suffer progressive damage, forcing boys into wheelchairs and onto respirators.

Today, a variety of approaches that attempt to either restore dystrophin or compensate for its loss are in the therapeutic pipeline.

“We’re at the point where lots of things are going into clinical trials,” says Louis Kunkel, PhD, who is credited with identifying dystrophin in 1987. “I call it the decade of therapy.” Full story »

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heart chip BarthIt was the variability that intrigued pediatric cardiologist William Pu, MD, about his patient with heart failure. The boy suffered from a rare genetic mitochondrial disorder called Barth syndrome. While he ultimately needed a heart transplant, his heart function seemed to vary day-to-day, consistent with reports in the medical literature.

“Often patients present in infancy with severe heart failure, then in childhood it gets much better, and in the teen years, much worse,” says Pu, of the Cardiology Research Center at Boston Children’s Hospital. “This reversibility suggests that this is a disease we should really be able to fix.”

Though it needs much more testing, a potential fix may now be in sight for Barth syndrome, which has no specific treatment and also causes skeletal muscle weakness and low white-blood-cell counts. It’s taken the work of multiple labs collaborating across institutional lines. Full story »

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De-risking drug development for orphan diseasePerhaps counter-intuitively, rare diseases can present attractive business opportunities for pharmaceutical companies. As discussed previously on Vector, they generally offer:

1) a population of patients with a high, unmet need, greatly lowering the bar to FDA approval

2) a closely networked disease community, greatly lowering the bar to creating disease registries and mounting clinical trials

3) well-studied disease pathways.

Recoiling from expensive failures of would-be blockbuster drugs, companies like Pfizer, Novartis, GlaxoSmithKline, Sanofi, Shire and Roche are embracing rare diseases, despite their small market sizes, because of their much clearer path to clinic. But in the current risk-averse industry environment, some projects are stalling. Industry may need more incentive to jump in—and Cydan Development is basing its business model on providing it. Full story »

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direct-to-consumer genetic testingLast November, the U.S. Food and Drug Administration issued a “cease and desist” order to 23andMe, a major purveyor of direct-to-consumer (DTC) genetic testing. In its letter to the company—issued after three prior warnings—the FDA reiterated its view that 23andMe’s Personal Genome Service (PGS) constitutes a medical device requiring further premarket evaluation:

FDA is concerned about the public health consequences of inaccurate results from the PGS device…we still do not have any assurance that the firm has analytically or clinically validated the PGS for its intended uses.

The FDA’s order, based on potential rather than actual medical harm, has generated a great deal of controversy. In a recent critique published in Nature, Robert Green, MD, MPH, of the Partners HealthCare Center for Personalized Genetic Medicine, and Nita Farahany, PhD, JD, of the Duke Institute for Genome Sciences and Policy, argued against regulating DTC genomic interpretation services as medical devices:

… doing so could put FDA regulations in greater tension with the First Amendment of the US Constitution, which protects the rights of individuals to receive information, and of ‘commercial speech’ ….the agency should avoid restricting consumer genomic testing unless faced with empirical evidence of harm. Full story »

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(Photo: Crossroads Foundation https://creativecommons.org/licenses/by/2.0/legalcode)

(Photo: Crossroads Foundation https://creativecommons.org/licenses/by/2.0/legalcode)

The United Nations global Millennium Development Goals (MDGs) for 2015 aim to cut mortality among children younger than 5 by two-thirds. As 2015 approaches, there’s a sense of hope: By 2012, the 1990 base annual figure of 12 million was nearly halved, in part through curbing infectious diseases.

However, two under-recognized, highly preventable chronic conditions—spina bifida and hydrocephalus—have not declined in low- and middle-income countries. Each year, there are an estimated 200,000 new cases of infant hydrocephalus in sub-Saharan Africa alone, and 100,000 neural tube defects in India alone. As other causes of death and disability recede, data suggest that spina bifida and hydrocephalus are gaining a larger share of mortality in young children.

A multi-institution conference at Boston Children’s Hospital on April 11 sounded a global call to action, convening a mix of surgeons, pediatric neurologists, international patient advocacy groups, food fortification proponents, health economists, obstetricians, neuroscientists and others. Many innovative approaches are being explored, including two that caught Vector’s eye. Full story »

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Neural stem cells Lou Gehrig's disease amyotrophic lateral sclerosis ALSUntil recently, most scientific knowledge about amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig’s disease, came from mouse studies. But new research is taking this incurable neurodegenerative condition to the dish, tapping induced pluripotent stem cells (iPS cells)—made from ALS patients’ skin cells—to create motor neurons. These motor neurons are being used not just to model how ALS works at the cellular level but also to screen potential drugs.

This work, taking place at the Harvard Stem Cell Institute (HSCI) in collaboration with Boston Children’s Hospital and Massachusetts General Hospital (MGH), has now paved the way for a clinical trial of a drug that might never otherwise have been thought of. Full story »

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In this screengrab from a Nature video, a siRNA, cradled by an argonaute protein, binds to a messenger RNA. (Watch the full video at: https://www.youtube.com/watch?v=cK-OGB1_ELE)

In this screen grab from a Nature video, a siRNA, cradled by an argonaute protein, binds to a messenger RNA. (More at www.youtube.com/watch?v=cK-OGB1_ELE)

RNA interference (RNAi) is a therapeutic technology that blocks gene expression with either small interfering RNAs (siRNA) or microRNAs (miRNA). RNAi’s discovery was considered transformative enough to earn the 2006 Nobel Prize for Physiology or Medicine, but from the start the challenge of delivering RNA-silencing therapeutics to the right tissues has hobbled efforts to use RNAi to treat patients.

Citing this challenge, the pharmaceutical giant Novartis is the latest major company to withdraw from RNAi research, following Merck and Roche. Forbes was prompted to write:

…for certain diseases where an RNAi therapeutant can be more readily introduced, such as the eye, or ‘privileged compartments’ such as the liver, RNAi still has potential. But given that these therapies would be expensive due to the high cost-of-goods involved in synthesizing these agents, they would have to be targeted to diseases where the cost of therapy would be justified by the beneficial medical effects. … to say that RNAi therapy will rival monoclonal antibodies in terms of revenue potential—well, that’s a bit of a stretch.

Barry Greene, COO of Alnylam Pharmaceuticals, a biotech that’s championed RNAi, countered in Fierce Drug Delivery: “Novartis pulling out is an exemplar of Big Pharma not being able to innovate, and historically they have never been able to innovate.” Full story »

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