Teaching an old drug a new trick to treat an ultra-rare red-blood-cell disease

Failed sickle-cell drug learns a new trick: hereditary xerocytosis

The National Institutes of Health maintains a library of drugs, the Clinical Collection, that are safe for humans but failed in clinical trials or didn’t make it to the market for other reasons. These compounds, numbering 450 to date, are just sitting on the shelf, waiting for a researcher to identify a disease process they might treat.

Repurposing such drugs could potentially save the pharmaceutical industry time and money. Getting a new drug from R&D to market currently takes $2 to 3 billion and 13 to 15 years. In contrast, some estimate that repurposing a safe drug could cost just $300 million and take just 6.5 years.

Pfizer, one of the biggest pharma companies in the world, saw the appeal. It just launched SpringWorks Therapeutics, a mission-driven company dedicated to reviving shelved drugs to treat underserved diseases. In its pipeline are experimental therapies to treat four diseases that currently have no cure.

One of the earliest-stage candidates is senicapoc.

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Organs-on-chips reveal breathing’s critical role in lung cancer development

Image of lung cancer cells grown alongside human lung small airway cells inside an organ-on-a-chip
Inside view of a lung cancer chip: Lung adenocarcinoma cells are grown as a tumor cell colony (blue) next to normal human lung small airway cells (purple). Credit: Wyss Institute at Harvard University

One of the biggest challenges facing cancer researchers — and lots of other medical researchers, in fact — is that experimental models cannot perfectly replicate human diseases in the laboratory.

That’s why human Organs-on-Chips, small devices that mimic human organ environments in an affordable and lifelike manner, have quickly been taken up into use by scientists in academic and industry labs and are being tested by the U.S. Food and Drug Administration.

Now, the chips have helped discover an important link between breathing mechanics and lung cancer behavior.

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Can rare pain syndromes point the way to new analgesics?

analgesic drug discovery could reduce prescription opioid use
Boston Children’s Hospital and Amgen will collaborate to discover and accelerate non-addicting pain drugs.

As the opioid epidemic deepens and drug overdoses increase, effective non-addicting painkillers are desperately needed. Efforts to discover new pain pathways to target with new drugs have thus far had little success. Other promising research is investigating triggerable local delivery systems for non-opioid nerve blockers, but it’s still in the early stages.

A new collaboration between Boston Children’s Hospital and the biopharmaceutical company Amgen is aimed at accelerating new pain treatments. Announced yesterday, it will revolve around patients with rare, perplexing pain syndromes. The scientists hope that the genetic variants they find in these patients will shed new light on pain biology and lead to new ways of controlling pain. 

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MATCHing precision medicine to all kids with cancer

Image of human neuroblastoma tumor cells. A new nationwide clinical trial called pediatric MATCH will utilize genomic sequencing to match children with individualized, targeted drugs matched to their tumor profile.
Human neuroblastoma cells.

A multi-center clinical trial is now offering nationwide genetic profiling services to pediatric and young adult cancer patients across the U.S. The goal is to identify gene mutations that can be individually matched with targeted drugs.

“This is the first-ever nationwide precision medicine clinical trial for pediatric cancer,” says pediatric oncologist Katherine Janeway, MD, clinical director of the solid tumor center at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.

Sponsored by the National Institute of Cancer (NCI) and the Children’s Oncology Group (COG), the so-called NCI-COG Pediatric MATCH trial will screen patients’ tumors for more than 160 gene mutations related to cancer. Nearly 1,000 patients are expected to participate in the trial and it is estimated that 10 percent of those patients will be matched with a targeted therapy.

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Meeting an unmet need: A surgical implant that grows with a child

Depiction of a growth-accommodating implant expanding in sync with a child's growing heart.
Artist’s rendering showing how a braided, tubular implant could grow in sync with a child’s heart valve. Credit: Randal McKenzie

Medical implants can save lives by correcting structural defects in the heart and other organs. But until now, the use of medical implants in children has been complicated by the fact that fixed-size implants cannot expand in tune with a child’s natural growth.

To address this unmet surgical need, a team of researchers from Boston Children’s Hospital and Brigham and Women’s Hospital have developed a growth-accommodating implant designed for use in a cardiac surgical procedure called a valve annuloplasty, which repairs leaking mitral and tricuspid valves in the heart. The innovation was reported today in Nature Biomedical Engineering.

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What do hospitals want from prospective digital health partners?

how digital health startups can better approach hospitals
How digital health startups can better approach hospitals.

How can the growing number of digital health startups sell their products to large-scale healthcare enterprises? Earlier this year, Rock Health, a San Francisco-based venture fund dedicated to digital health, conducted 30-minute interviews with executives at multiple startups and a few large healthcare organizations. They identified several key sticking points: navigating the internal complexities of hospitals, finding the right buyer, identifying the product’s value proposition and relevance to the hospital and avoiding “death by pilot.”

Now, in a Rock Health podcast, John Brownstein, PhD, Chief Innovation Officer at Boston Children’s Hospital’s Innovation and Digital Health Accelerator and Adam Landman, MD, MS, MIS, MHS, Chief Information Officer at Brigham and Women’s Hospital and part of its Innovation Hub, offer further tips from the inside. They were hosted by Rock Health’s director of research, Megan Zweig.

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Gene therapy halts progression of cerebral adrenoleukodystrophy in clinical trial

David Williams, MD, the principal investigator of the clinical trial, discusses gene therapy and its impact on children with adrenoleukodystrophy

Adrenoleukodystrophy — depicted in the 1992 movie “Lorenzo’s Oil” — is a genetic disease that most severely affects boys. Caused by a defective gene on the X chromosome, it triggers a build-up of fatty acids that damage the protective myelin sheaths of the brain’s neurons, leading to cognitive and motor impairment. The most devastating form of the disease is cerebral adrenoleukodystrophy (CALD), marked by loss of myelin and brain inflammation. Without treatment, CALD ultimately leads to a vegetative state, typically claiming boys’ lives within 10 years of diagnosis.

But now, a breakthrough treatment is offering hope to families affected by adrenoleukodystrophy. A gene therapy treatment effectively stabilized CALD’s progression in 88 percent of patients, according to clinical trial results reported in the New England Journal of Medicine. The study was led by researchers from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Massachusetts General Hospital.

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Dock Health’s shared ‘to do’ list for clinical teams — so basic, so necessary

Dock Health - a shared to-do list for clinical teams - could ease clinical burnout

While something as simple as a “to-do list” might seem trivial, a secure hub to store, prioritize and assign clinical and administrative tasks could be game-changing in healthcare.

Michael Docktor, MD, of Boston Children’s Hospital made this case yesterday at the Health 2.0 Conference in Santa Clara, Calif. He demonstrated Dock Health, a secure iOS mobile and web application that helps medical teams manage the numerous tasks that fall under clinical care. The idea was born in his gastroenterology practice at Boston Children’s and was incubated by the hospital’s Innovation and Digital Health Accelerator (IDHA).

“In an average day in clinic, I might see 15 patients and get 75 emails, 10 secure messages, three pages and five [electronic medical record] messages in my inbox,” Docktor writes on Medium. “Not too long ago, some emails were from frustrated colleagues, asking me to do something for a second or third time. Sadly, some were from parents of my patients, kindly reminding me that they were sitting in the lab waiting for the orders I forgot to place or trying to book their colonoscopy, for which I had forgotten to submit the form.”

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How do we sense moonlight? Daylight? There’s a cell for that

environmental light sensing must span a wide spectrum of light intensities

To run our circadian clocks, regulate sleep and control hormone levels, we rely on light-sensing neurons known as M1 ganglion cell photoreceptors. Separate from the retina’s rods and cones, M1 cells specialize in “non-image” vision and function even in people who are blind.

Reporting in today’s Cell, neuroscientists at Boston Children’s Hospital describe an unexpected system that M1 cells use to sense changing amounts of environmental illumination. They found that the cells divvy up the job, with particular neurons tuned to different ranges of light intensity.

“As the earth turns, the level of illumination ranges across many orders of magnitude, from starlight to full daylight,” says Michael Do, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, senior author on the paper. “How do you build a sensory system that covers such a broad range? It seems like a straightforward problem, but the solution we found was a lot more complex than expected.”

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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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