Stories about: Orphan diseases

Why we need more research into childhood cancer

WilliamsDavidDSC_0056PreviewlargeDavid A. Williams, MD, is chief of hematology/oncology at Boston Children’s Hospital and associate chairman of pediatric oncology at Dana-Farber Cancer Institute. This column was first published on Huffington Post.

The fact that childhood cancer is, thankfully, rare belies the fact that it is the leading cause of disease-related death in U.S. children age 1 to 19. The number of people with a direct stake in expanding research into pediatric cancer is quite large, well beyond the small number of children with cancer and their families. Not only are the life-long contributions of children cured of cancer enormous, but understanding cancers of young children could also hold the key to understanding a broad range of adult cancers. The time is ripe to allocate more resources, public and private, to research on pediatric cancer.

In an age of increased understanding of the genetic basis of diseases, one thing is striking about many childhood cancers. They are relatively “quiet” cancers, with very few mutations of the DNA. Young children haven’t lived long enough to acquire the large number of mutations that create the background “noise” associated with years of living. This makes it much easier to pinpoint the relevant genetic abnormalities in a young child’s cancer.

Add to this the growing realization that biology, including how various tumors use common “pathways,” is a major factor in how the cancer responds to treatment. Thus, a mechanism that’s relatively easier to observe in the cancers of young children could help scientists understand cancers in adults, in whom the same mechanism is hidden amid the clutter of mutations acquired over a longer life.

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Rare disease: A difficult therapeutic path

Rare disease panelWhen a rare disease affects you or your family, it doesn’t seem rare. Add them all up, and rare diseases aren’t all that uncommon. What’s rare is for patients to receive effective treatments.

“There are 7,000 rare diseases, and under 400 approved drugs,” says Peter Saltonstall, president and CEO of the National Organization for Rare Disorders (NORD), “so there’s a huge opportunity there to try to develop more drugs.”

Saltonstall spoke today with five other panelists at Boston Children’s Hospital’s Global Pediatric Innovation Summit + Awards in a session titled, “Rare diseases: Lessons from the path less chosen.” David Meeker, MD, president and CEO of Genzyme, moderated.

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Gene discovery: When you’re the only patient with the disease

Gene Discovery Core rare diseaseVector took a moment this morning at the Boston Children’s Hospital Global Pediatric Innovation Summit + Awards to catch up with the Gene Discovery Core at the Manton Center for Orphan Disease Research. Its exhibition table doesn’t have fancy mannequins or flashy screens, but this team is rocking genetics and genomics, one patient at a time.

The usual methods for finding disease-causing genes don’t work for many patients who walk in the doors of Boston Children’s, or who mail in samples from all over the world. They may be one of just a handful of patients in the world with their condition—which may not even have a name yet.

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A double-shot of good news for SCID: Promising transplant and gene therapy data

Hematopoietic hierarchy aging blood cell hematopoietic stem cell blood disorder Derrick Rossi
Blood-forming hematopoietic stem cells (top) give rise to all blood and immune cell types. In children with SCID, the steps leading to immune cells are broken.

In the world of fatal congenital immunodeficiency diseases, good news is always welcome, because most patients die before their first birthday if not treated. Babies with severe combined immunodeficiency disease, aka SCID or the “bubble boy disease,” now have more hope for survival thanks to two pieces of good news.

Transplants are looking up

First came a July paper in the New England Journal of Medicine (NEJM) by the Primary Immune Deficiency Treatment Consortium. This North American collaborative analyzed a decade’s worth of outcomes of hematopoietic stem cell transplant (HSCT), currently the only standard treatment option for SCID that has a chance of providing a permanent cure.

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Gene therapy gets in the ring with another disease

Emir Seyrek Wiskott-Aldrich syndrome WAS gene therapy Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Emir Seyrek was the first patient with Wiskott-Aldrich syndrome to be treated in the U.S. in an international gene therapy trial.

Seeing that his mother, Kadriye, wasn’t looking, Emir Seyrek got an impish grin on his face, the kind only a two-year-old can have. He quietly dumped his bowl of dry cereal out on his bed and, with another quick look towards his mother, proceeded to pulverize the flakes to dust with his toy truck. The rest of the room burst out laughing while his mother scolded him. Despite the scolding, though, the impish grin remained.

It was hard to believe that he arrived from Turkey six months earlier fighting a host of bacterial and viral infections. Emir was born with Wiskott-Aldrich syndrome (WAS), a genetic immunodeficiency that left him with a defective immune system. He was here because he was the first patient—of two so far—to take part in an international trial of a new gene therapy treatment for WAS at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. And that day he was having his final checkup at Boston Children’s Hospital’s Clinical and Translational Study Unit before going home.

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Duchenne muscular dystrophy: The decade of therapy

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

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Rett syndrome sees glimmer of hope in Phase I trial

Hope for Rett syndrome?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.

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We have a $1,000 genome. Now what?

Abstract model of the genome morphing into human shape representing clinical genomics.The Human Genome Project’s push to completely sequence the human genome ran a tab of roughly $2.7 billion and required the efforts of 20 research centers around the world using rooms full of equipment.

But that was using technology from the 1990s to early-2000s. As by a panel of genomics experts from industry and academia pointed out at last week’s National Pediatric Innovation Summit + Awards, a scientist in a single laboratory today can sequence a genome for as little as $1,000, making sequencing almost a medical commodity.

Now what? How do we go about making clinical genomics an everyday thing? The discussion left the answer to that question—and the other questions it raises—unclear. While the panelists expressed excitement about what’s possible, they cited great uncertainty among doctors, scientists, patients, payers, companies and regulators about how to make clinical genomics work.

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Children as ‘orphans’ of innovation: Finding good homes

Cows provided tuberculosis-free milk to Boston Children's Hospital in 1919.
An early innovation: Specially bred cows graze in front of Boston Children’s Hospital in 1919, providing safe, tuberculosis-free milk for patients.
Clinicians wanting to develop new devices and treatments for children face formidable barriers: regulators’ need to protect the most vulnerable coupled with a lack of commercial interest. But determined innovators do have options, including creative funding sources, says Thomas Krummel, MD, director of surgical innovation at Stanford Medical School.

“Technology developed specifically for children has been a low priority,” Krummel began at a two-part talk at Boston Children’s Hospital this summer (read our coverage of the other part). “The FDA barriers are incredibly high, and ultimately, investors just demand returns that pediatric markets won’t necessarily deliver.”

As Krummel detailed, the FDA barriers are there for a reason: a past history of ethical abuses in human subjects research. In 1966, physician Henry Beecher, MD, exposed many examples in The New England Journal of Medicine, such as withholding effective treatment for the sake of research, proceeding with a treatment despite recognized hazards, or failing to disclose risk to patients. Institutional Review Boards (IRBs) arose in the mid-1970s to protect research subjects—protections that are especially strict when that research is done in children.

But there’s also a deep-seated reluctance to break with the status quo.

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Blood stem cell transplants for metabolic disorders of the brain?

Bone marrow being extracted for a hematopoietic stem cell transplant
A patient’s bone marrow is extracted for a hematopoietic stem cell transplant, or HSCT. Once just a last-resort treatment for cancer, HSCTs are now used for a growing list of conditions, including certain metabolic disorders affecting the brain. (US Navy/Wikimedia Commons)

The history of hematopoietic stem cell transplant (HSCT) starts with severe cancers of the blood or immune system, like relapsed leukemias or lymphomas. Today, HSCTs are no longer solely the treatment of last resort for cancer but is used to treat a growing list of pediatric and adult conditions.

Most of these are cancers and blood disorders, but in recent years, a new frontier has opened up for HSCT: treatment of metabolic diseases, in particular, ones that affect the function of the brain.

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