Honoring rare disease ‘citizen scientists’

citizen scientists

The global theme of this year’s Rare Disease Day (February 28) is research, and in keeping with that, we salute a very important group of people: citizen scientists. These can-do patients and family members are putting previously undiagnosed rare diseases on the map and driving the search for treatments. Citizen scientists play multiple roles: They keep scientists focused on therapeutic development, conduct online research to connect ideas, set up patient networks and data registries, raise money and start companies. They’ve earned a voice in clinical trial design and were instrumental in the passage of the 21st Century Cures Act.

Meet a few citizen scientists who have inspired us recently.

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4 tactical steps to designing for digital health

design digital health

Third in an ongoing series of Innovator’s Roadmap posts from Boston Children’s Hospital’s Innovation & Digital Health Accelerator (IDHA). Matt Murphy is Innovation Lead at IDHA.

We recently provided market sizing guidelines for healthcare innovators — strategies to help you determine your innovation’s total number of potential users and your sales opportunities. Next, we’ll take you through our approach to designing digital health products.

The research and design phase is a critical step in the development and commercialization of digital health innovations. This phase is often referred to as user-centered design or human factors design. It requires a significant investment in understanding your users (including clinicians, clinical teams, patients and/or caregivers) and their pain points (problems they repeatedly experience) before developing a technology-based solution.

In our initial consultations with innovators at Boston Children’s Hospital, we spend only a small amount of time discussing end technology solutions. Instead, we seek to understand the intended users, their pain points and how they will interact with the innovation, including clinical, workflow and business considerations.

It’s market research taken a step further. We recommend you follow a specific four-step procedure to optimize the research and design phase.

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Abraham Rudolph, MD: The path of a pediatric cardiology pioneer

Abraham Rudolph MD
Rudolph (left) at Boston Children’s Hospital with Cardiologist-in-Chief Alexander Nadas, MD, c. 1958.

Abraham Rudolph, MD, who recently turned 93, has watched his chosen corner of the medical profession — pediatric cardiology — grow from rudimentary beginnings into a robust, multivariate discipline. Yet while his name is known worldwide in pediatric cardiology circles, he entered cardiology more than 50 years ago only by happenstance.

Born in South Africa in 1924, Rudolph came to the United States in 1951 to train in cardiology by invitation of Charles Janeway, MD, then Physician-in-Chief at Boston Children’s Hospital. Concerned about providing for his wife and newborn daughter, he chose cardiology over hematology or neurology because it offered a salary; many other physician-training opportunities at the time were unpaid. That first year, as the hospital’s first cardiology fellow, he made $3,000 — thanks to a family donation.

He stayed on for nine years, becoming director of the cardiac catheterization laboratory. There he found his focus.

“I became more and more interested in the physiology of the circulation, particularly the problems surrounding infancy,” he said in a 1996 interview with the American Academy of Pediatrics. “At that time, there were relatively few places that were doing anything about infants with heart disease. Most of the emphasis was on older children.”

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Science Seen: Brain myelination in tuberous sclerosis complex

tuberous sclerosis brain myelination improved with CTGF deletion

Tuberous sclerosis complex (TSC) strikes about 1 in 6,000 people and is marked by numerous benign tumors in the brain, kidneys, heart, lungs and other tissues. Children with TSC often have epilepsy, intellectual disability and/or autism, showing disorganized white matter in their brains. Work in the lab of Mustafa Sahin, MD, PhD, has shown that the TSC1 mutation disrupts the brain’s ability to adequately wrap its nerve fibers in myelin, the insulating coating that enhances nerves’ ability to conduct signals. A new study from the lab shows why: neurons lacking functional TSC1 secrete increased amounts of connective tissue growth factor (CTGF). This impairs the development of oligodendrocytes, the cells that do the myelinating. Here, electron microscopy in a TSC mouse model shows a decreased number of nerve fibers wrapped in myelin (dark ovals) on the left. On the right, genetic deletion of CTGF increases myelination. Sahin plans to delve further to develop potential pharmaceutical approaches to restore myelination in TSC. Read more in the Journal of Experimental Medicine. (Image: Ebru Ercan et al.)

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Stem cell workaround cracks open new leads in Diamond Blackfan anemia

Diamond Blackfan anemia iPS cells hematopoietic progenitor cells
Though not bona-fide stem cells, hematopoietic progenitor cells produce red blood cells when exposed to certain chemicals. Could some of these compounds lead to new drugs for Diamond Blackfan anemia?

Diamond Blackfan anemia (DBA) has long been a disease waiting for a cure. First described in 1938 by Louis K. Diamond, MD, of Boston Children’s Hospital and his mentor, Kenneth Blackfan, MD, the rare, severe blood disorder prevents the bone marrow from making enough red blood cells. It’s been linked to mutations affecting a variety of proteins in ribosomes, the cellular organelles that themselves build proteins. The first mutation was reported in 1999.

But scientists have been unable to connect the dots and turn that knowledge into new treatments for DBA. Steroids are still the mainstay of care, and they help only about half of patients. Some people eventually stop responding, and many are forced onto lifelong blood transfusions.

Researchers have tried for years to isolate and study patients’ blood stem cells, hoping to recapture the disease process and gather new therapeutic leads. Some blood stem cells have been isolated, but they’re very rare and can’t be replicated in enough numbers to be useful for research.

Induced pluripotent stem (iPS) cells, first created in 2006 from donor skin cells, seemed to raise new hope. They can theoretically generate virtually any specialized cell, allowing scientists model a patient’s disease in a dish and test potential drugs.

There’s been just one hitch. “People quickly ran into problems with blood,” says hematology researcher Sergei Doulatov, PhD. “iPS cells have been hard to instruct when it comes to making blood cells.”

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Gene therapy restores whisper-fine hearing, balance in Usher syndrome mice

gene therapy for deafness
Sensory hair cells contain tiny cilia that get wiggled by incoming sound waves, sparking a signal to the brain that ultimately translates to hearing. Gene therapy restored this tidy “V” formation. (Credit: Gwenaelle Géléoc and Artur Indzkykulian)

The ear is a part of the body that’s readily accessible to gene therapy: You can inject a gene delivery vector (typically a harmless virus) and it has a good chance of staying put. But will it ferry the corrected gene into the cells of the hearing and/or vestibular organs where it’s most needed?

Back in 2015, a Boston Children’s Hospital/Harvard Medical School team reported using gene therapy to restore rudimentary hearing in mice with genetic deafness. Previously unresponsive mice began jumping when exposed to abrupt loud sounds. But the vector used could get the corrected genes only into the cochlea’s inner hair cells. To really restore significant hearing, the outer hair cells need to be treated too.

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A guide to market sizing for healthcare innovators

market sizing healthcare innovation

Second in a series of Innovator’s Roadmap posts from Boston Children’s Hospital’s Innovation & Digital Health Accelerator (IDHA). Matt Murphy is Innovation Lead at IDHA.

We recently published some helpful tips on how to create a business model that accelerates and operationalizes a healthcare innovation. But a business model — and the unique value proposition you’ll offer to your users or customers — cannot exist on its own. It must serve a specific market or population.

Who are your users? And how many potential users would your product serve? Market sizing will enable you to answer these questions and others as you determine the financial opportunity and economic sustainability of your innovation.

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Why I’m tall and you’re short: GIANT effort finds rare, potent height genes

height genes that make us tall or short

Height is the “poster child” of complex genetic traits, meaning that it’s influenced by multiple genetic variants working together. Because height is easy to measure, it’s a relatively simple model for understanding traits produced by not one gene, but many.

“Mastering the complex genetics of height may give us a blueprint for studying multifactorial disorders that have eluded our complete understanding, such as diabetes and heart disease,” says Joel Hirschhorn, MD, PhD, a pediatric endocrinologist and researcher at Boston Children’s Hospital and the Broad Institute of MIT and Harvard.

Hirschhorn chairs the Genetic Investigation of Anthropometric Traits (GIANT) Consortium, an international group that’s just probed more deeply into the genetics of height than ever before. Its findings, reported today in Nature, reveal previously unknown biological pathways tied to height.

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Seeking a way to keep organs young

Images of mouse hearts with fibrosis
These mouse hearts show differing levels of fibrosis (blue) resulting from cardiac stress. New Boston Children’s Hospital research suggests certain therapies could prevent or reduce fibrosis, like we see in the center and right images.

The wear and tear of life takes a cumulative toll on our bodies. Our organs gradually stiffen through fibrosis, which is a process that deposits tough collagen in our body tissue. Fibrosis happens little by little, each time we experience illness or injury. Eventually, this causes our health to decline.

“As we age, we typically accumulate more fibrosis and our organs become dysfunctional,” says Denisa Wagner, PhD, the Edwin Cohn Professor of Pediatrics in the Program in Cellular and Molecular Medicine and a member of the Division of Hematology/Oncology at Boston Children’s Hospital and Harvard Medical School.

Ironically, fibrosis can stem from our own immune system’s attempt to defend us during injury, stress-related illness, environmental factors and even common infections.

But a Boston Children’s team of scientists thinks preventative therapies could be on the horizon. A study by Wagner and her team, published recently by the Journal of Experimental Medicine, pinpoints a gene responsible for fibrosis and identifies some possible therapeutic solutions.

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A healthcare Innovator’s Roadmap: 4 steps for developing a business model

healthcare innovation business plan

First in an on-going series of Innovator’s Roadmap posts from Boston Children’s Hospital’s Innovation & Digital Health Accelerator (IDHA). Matt Murphy is Innovation Lead at IDHA.

Seeing an idea go from the lab or clinic to the wider world is exciting. However, clinicians, researchers and administrators don’t always have the time or resources to take their innovations to the next step — that is, build them to scale. At Boston Children’s Hospital, the Innovation & Digital Health Accelerator (IDHA), comprised of 50+ researchers, business strategists and technologists, is dedicated to just that: We identify and vet high-priority health technology innovations at the hospital and provide the resources, funding and momentum to accelerate their development and commercialization.

To date, Boston Children’s has spun off more than 25 startup companies developed directly from clinical and research pain points. Some startups, like Neuromotion and Circulation, stand on their own. Others, including Epidemico, have been acquired by industry leaders. Through this experience, IDHA created the Innovator’s Roadmap – a comprehensive resource for taking ideas from concept to commercially available, impactful, economically sustainable products.

In this first installment, we look at the critical first step: understanding and justifying the business value of a technology or service by developing a business model.

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