Stories about: Orphan diseases

An unusual dog, a new approach to muscular dystrophy: Stimulating a protective gene

Vieira with Ringo
Vieira with Ringo

Ringo was a golden retriever that defied the odds. Despite having the gene mutation for Duchenne muscular dystrophy (DMD), he remained healthy. And he’s provided a new lead for boosting muscle strength in DMD, one of the most common forms of muscular dystrophy. Unlike other dogs with the dystrophin mutation, who are weak and typically die by 2 years of age, Ringo was able to walk and run normally and lived to the age of 11, within the normal range for golden retrievers.

What made Ringo so resilient?

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Two big wins for rare disease

Two new developments offer glimmers of hope to patients with rare, hard-to-diagnose conditions—validation of the power of crowd sourcing and the prospect of bringing cognitive computing to rare disease diagnosis. Both developments were announced at the Boston Children’s Hospital Global Pediatric Innovation Summit + Awards (#PedInno15).

The crowd-sourcing challenge, CLARITY Undiagnosed, yesterday announced the findings of 21 teams that competed from seven countries. The winning team, Nationwide Children’s Hospital (Columbus, OH), was awarded $25,000. Invitae Corporation (San Francisco) and Wuxi NextCODE Genomics (Cambridge, MA) were named runners-up.

Each team received DNA sequences and clinical data from five families whose illnesses had eluded many prior diagnostic attempts—in some cases, even prior genomic sequencing.

“These were the toughest of the tough,” says Alan Beggs, PhD, co-organizer of CLARITY Undiagnosed and director of the Manton Center for Orphan Disease Research at Boston Children’s.

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An online portal for undiagnosed patients


Prospects are looking up for patients who have no explanation for their symptoms despite extensive investigations and testing. There’s a growing revolution in DNA diagnostics (see yesterday’s example) and ongoing work to bring clarity and meaning to sequencing data. Patients with similar symptoms can find each other like never before, and are increasingly empowered to lead in research and discovery.

Another small but important development was announced yesterday by the National Institutes of Health. The NIH’s Undiagnosed Diseases Network (UDN) has opened up a one-stop online portal called the UDN Gateway where patients and families can apply for access to expert team analysis and testing. (A referral letter from a provider is required.)

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Focused genetic testing approach ends a 32-year diagnostic journey

Claritas-JackieSmith3-croppedSome 7,500 rare disorders are known to be caused by single-gene mutations. Most of these disorders first appear at birth or in childhood, and for about half, the responsible gene has been identified. Yet, on average, families with rare disorders spend 12 years searching before getting a correct diagnosis.

Jackie Smith, a 35-year-old mother of two, searched for 32 years for the cause of her muscular weakness. Her parents knew something was wrong soon after she was born. At first, because her ankles turned in, they thought she was bow-legged.

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Undiagnosed families hold on as genome competitors look for explanations

undiagnosed patients await answersThe CLARITY Undiagnosed Challenge is heating up. Biomedical teams from seven countries are racing to interpret DNA sequences from five families affected with undiagnosed illnesses—some with gravely ill children, some already bereaved, all desperate for answers.

In July, the 26 competing teams received whole-genome and whole-exome sequence data from each patient and close family members, along with clinical notes and patient videos. Their reports, due September 21, will be judged by an independent panel based on:

  • the methods used to analyze and interpret the sequence data
  • the ability to synthesize the information
  • clinical usefulness, care recommendations and “next steps.”
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So far, so good for gene therapy patient Emir Seyrek

Emir Seyrek gene therapy Wiskott-Aldrich ThrivingRemember Emir Seyrek, the Turkish boy who last year was the first patient in gene therapy trial for a genetic immunodeficiency called Wiskott-Aldrich Syndrome? Emir traveled back to the U.S. earlier this month for an annual follow-up visit with his care team at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. The news was quite good.

“Emir is the star of the trial,” Sung-Yun Pai, MD—a Dana-Farber/Boston Children’s gene therapy and immunodeficiency transplant specialist and lead (along with David Williams, MD, and Luigi Notarangelo, MD) of the U.S. arm of the trial—tells our sister blog, Thriving. “He has the highest platelet count of all of the children who have gone through gene therapy with this vector so far. His immune function is excellent, and we have no worries whatsoever from a bleeding standpoint. He’s perfectly safe to play like a normal child.”

Learn more about Emir’s progress on Thriving.


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The autism-GI link: Inflammatory bowel disease found more prevalent in ASD patients

brain gut connection autism IBD ASDReports from parents and a growing number of studies over the past 10 to 15 years suggest that children with autism spectrum disorder (ASD), especially more severe ASD, are prone to gastrointestinal disorders. Researchers have attributed the association to altered GI microbiota, abnormal intestinal physiology, immune alterations and other mechanisms. Some speculate that the connection results from unusual eating patterns in children with ASD.

A 2012 study led by bioinformatician Isaac Kohane, MD, PhD, of Boston Children’s Hospital and Harvard Medical School grouped autism patients according to the gene expression patterns in their blood, and one group had altered immunologic and inflammatory pathways. A more recent study went a step further, finding similar gene expression profiles in the intestines of children with ASD and those with inflammatory bowel disease (IBD).

Looking at IBD (Crohn’s and colitis) sets the bar a little higher, since IBD is uncommon and also unlikely to be caused by dietary factors (though it can certainly be aggravated by them). In a new study in the journal Inflammatory Bowel Disease, Kohane and colleagues crunched three large databases to create what they believe is the largest ASD/IBD study to date.

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When your child isn’t just rare, but probably one of a kind

Savoie at home with 4-year-old Esmé in New York.
Savoie at home with 4-year-old Esmé in New York.

Hillary Savoie, PhD, founder and director of The Cute Syndrome Foundation, is author of Around And Into The Unknown, chronicling her family’s journey to find a diagnosis for Esmé, and Whoosh, about coming to terms with Esmé’s early medical complications.

I think my daughter Esmé is extraordinarily unique—from her tiny pudgy feet that she likes to stuff in her mouth to her beautifully lashed blue eyes and outrageously untamed hair. It’s a mom thing. I guess it is a symptom of loving another person more than life itself.

But my daughter is also unusual in a more scientific way: in her genes. 

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Power to the people: Citizen science meets precision medicine for rare disease

At this recent GoldLab Symposium presentation in Colorado, parent Matt Might shows how it’s done.

People credit rapid next-generation gene sequencing for the increased pace of medical discovery. But patients and their families—especially those with rare or undiagnosed conditions—are emerging as the true engines of precision medicine. Racing against the clock to save their children, parents are building databanks, connecting scientific dots and fueling therapeutic advances that could otherwise take a decade or more to happen.

“There’s a culture shift,” said Isaac Kohane, MD, PhD, chair of Harvard Medical School’s Department of Biomedical Informatics (DBMI), which hosted a conference titled Precision Medicine 2015: Patient Driven in late June. “A culture shift where patients feel empowered morally and intellectually to lead in precision medicine research and delivery.”

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Gene therapy to germline editing: Promises, challenges, ethics

A report this April rocked the scientific world: scientists in China reported editing the genomes of human embryos using CRISPR/Cas9 technology. It was a limited success: of 86 embryos injected with CRISPR/Cas9, only 71 survived and only 4 had their target gene successfully edited. The edits didn’t take in every cell, creating a mosaic pattern, and worse, unwanted DNA mutations were introduced.

“Their study should give pause to any practitioner who thinks the technology is ready for testing to eradicate disease genes during [in vitro fertilization],” George Q. Daley, MD, PhD, director of the Stem Cell Transplantation Program at Boston Children’s Hospital, told The New York Times. “This is an unsafe procedure and should not be practiced at this time, and perhaps never.”

As Daley detailed last week in his excellent presentation at Harvard Medical School’s Talks@12 series, the report reignited an ethical debate around tampering with life that’s hummed around genetic and stem cell research for decades. What the Chinese report adds is the theoretical capability of not just changing your genetic makeup, but changing the DNA you pass on to your children.

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