Stories about: rare disease

With no time to lose, parents drive CMT4J gene therapy forward

CMT4J
Talia Duff’s disorder, CMT4J, is a rare form of Charcot-Marie-Tooth. It has been modeled in mice that will soon undergo a test of gene therapy, largely through her parents’ behind-the-scenes work.

In honor of Rare Disease Day (Feb. 28), we salute “citizen scientists” Jocelyn and John Duff.

When Talia Duff was born, her parents realized life would be different, but still joyful. They were quickly adopted by the Down syndrome parent community and fell in love with Talia and her bright smile.

But when Talia was about four, it was clear she had a true problem. She started losing strength in her arms and legs. When she got sick, which was often, the weakness seemed to accelerate.

Talia was initially diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), an autoimmune disease in which the body attacks its own nerve fibers. Treated with IV immunoglobulin infusions to curb the inflammation, she seemed to grow stronger — but only for a time. Adding prednisone, a steroid, seemed to help. But it also caused bone loss, and Talia began having spine fractures.

“We tried a lot of different things, but she never got 100 percent better,” says Regina Laine, NP, who has been following Talia in Boston Children’s Hospital’s Neuromuscular Center the past several years, together with Basil Darras, MD.That’s when we decided to readdress the possibility that it was genetic.”

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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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Rare blood disorder sideroblastic anemia slowly reveals its genetic secrets

congenital sideroblastic anemia
Regardless of the gene, all patients with sideroblastic anemia have sideroblasts: red blood cell precursors with abnormal iron deposits in mitochondria, shown here ringing the cell nucleus. (Paulo Henrique Orlandi Mourao/Wikimedia)

A decade ago, Brooks McMurray’s routine check-up was anything but routine. The suburban Boston boy’s spleen was enlarged. His red blood cell count was low and the cells were very small and very pale, which suggested a serious iron deficiency anemia. The family pediatrician referred McMurray, now a 19-year-old college freshman, to Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.

There hematologists discovered the boy had unexpectedly high iron levels. Together with pathologist Mark Fleming, MD, DPhil, they solved the mystery. McMurray has congenital sideroblastic anemia, an inherited blood disorder so rare that fewer than 1,000 cases have been reported worldwide. Iron was getting stuck in the wrong place in the precursor red blood cells developing in his bone marrow.

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2017 predictions for biomedicine

2017 predictions for biomedicine

David Williams, MD, is Boston Children’s Hospital’s newly appointed Chief Scientific Officer. He is also president of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and director of Clinical and Translational Research at Boston Children’s. Vector connected with him to get his forecast on where biomedical research and therapeutic development will go in the year ahead.

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Why we’re glad the Cures Act passed: Its provisions benefit children

Cures Act children
Via @POTUS

Amy Judge DeLong is manager of Federal Government Relations at Boston Children’s Hospital.

In the midst of a seismic shift in Presidential administrations and anticipation of the incoming Congress, a landmark medical research bill with several provisions important to children cleared the lame duck session of Congress. The 21st Century Cures Act (Cures) is the end result of nearly three years of bipartisan Congressional activity. Last week, it was signed into law.

Cures includes scores of provisions aimed at strengthening National Institutes of Health funding for medical research and accelerating review efforts at the Food and Drug Administration. The law cleared Congress with overwhelming majorities, an example of bipartisanship that may be challenged in the months ahead.

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The 21st Century Cures Act: Addressing unmet needs in children with rare disease

21st Century Cures Act and children
Among its other provisions, the Cures Act would advance implementation of the 2013 National Pediatric Research Network Act, boosting therapeutic development for rare childhood diseases.

Medical solutions often require countless hours of investigation, months of testing and monitoring, years of post-trial and market analysis and billions of dollars of investment — with no certainty of success.

Last year, after years of groundwork, the U.S. House of Representatives passed the 21st Century Cures Act. A companion measure is being developed in the Senate, and stakeholders are optimistic that agreement on a package — even a slimmed down bill — could happen this year.

While Congress has addressed research and medical product regulatory needs before, the Cures Act has been unique in its comprehensive approach, looking at all elements of the research spectrum — from basic discovery science to translational research to regulatory review. It would upgrade the National Institutes of Health’s research capabilities and update the Food and Drug Administration’s approval policies to get new drugs and devices to the clinic sooner.

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Citizen science: Genetic bone disease fuels a teen’s passion for research

citizen science

When I was just 3 months old, I was diagnosed with fibular hemimelia, a rare genetic condition that affects about 1 in 50,000 people. It manifests itself as the lack of the fibula bone, a key structural bone in the lower leg that provides major stability in the ankle and knee.

Fibular hemimelia leads to a severe leg length discrepancy — which, in my case, would have amounted to over 6 inches without treatment. Prior to my time at Boston Children’s Hospital, the go-to cure was amputation — replacing my lower leg with a series of prostheses.

Luckily, at the time of my diagnosis, leg-lengthening surgeries were just being approved in the U.S. My parents couldn’t bear to part with my leg, so over the course of 18 years, I have undergone 13 procedures to combat my leg-length difference, starting at age 5. This early exposure to the medical field, coupled with encouragement from teachers, led to a passion for science.

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Citizen science: Giving patients a voice in drug development

citizen science patient voice drug development

There’s a natural tension between wanting the FDA to ensure safety and efficacy before a drug enters the market and wanting to speed up what many view as a glacially slow approval process. The rare disease community tends to fall in the second camp, and has become increasingly vocal in calling for more clinical trials, more flexibility in their design and redefinition of what constitutes a benefit.

ALS advocates, for example, have called for a parallel track, “in which FDA provides an early approval based on limited data, and then continues the learning process in a confirmatory clinical trial and if needed, patient registries to collect additional data from patients receiving the drug outside the clinical trial…”

Recent legislation is encouraging patient engagement in drug development, especially for conditions with profound unmet medical needs. In its 2012 iteration, the Prescription Drug User Fees Act (PDUFA) introduced public meetings to get input from the patient community, captured in a series of informative white papers.

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Hunting rare cancers to ground

rare cancers
(UGREEN 3S / Shutterstock)

As we’ve seen this week on Vector, some rare childhood cancers such as medulloblastoma and neuroblastoma are starting to give up their molecular secrets, raising the possibility (and in medulloblastoma’s case, the reality) of precision treatments. Many cancers, though, are so rare that there aren’t even cell lines in which to study them. Yet they could hold important insights. The first tumor suppressor gene, Rb, was discovered in retinoblastoma, a cancer affecting a mere 500 U.S. children each year.

Doctors often have no clear consensus for diagnosing and treating rare cancers, and outcomes tend to be poor in both children and adults. Andrew Hong, MD, a postdoctoral fellow in the Broad Institute’s Cancer Program and a pediatric oncologist at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, is part of a research team that wants to fix that.

Armed with recent advances in culture technology, the scientists aim to engineer cell lines for as many rare cancers as they can get samples for — and then interrogate them for therapeutic targets. A proof-of-concept published in Nature Communications last month finds a lot of potential in their approach. Read more on Broad Minded, the Broad Institute’s science blog.

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Mom-entrepreneur forms gene therapy company to tackle Sanfilippo syndrome

Karen and Ornella Aiach Sanfilippo gene therapy

Sanfilippo syndrome A is a neurodegenerative condition caused by a genetic error in metabolism: because of a missing enzyme, long-chained sugar molecules cannot be broken down. Toxic substrates accumulate in cells, causing a rapid cognitive decline and, later, motor decline. Most affected children die in their teens or earlier.

There is no treatment, and when Karen Aiach’s daughter Ornella was diagnosed with Sanfilippo syndrome A, no companies were even working on the disease.

As a mother, Aiach could not accept that.

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