Stories about: Stuart Orkin

Science then & now: Progress that you can see

Click and drag to compare and contrast archive photos from the lab with current-day images of research at Boston Children’s Hospital.

Then, 1986: Stuart H. Orkin, MD, examines the DNA sequence of a gene.

Now, 2017: Today, Orkin is associate chief of Hematology/Oncology and chairman of Pediatric Oncology at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center (DF/BC). In this photo, he examines a rendering of a gene regulatory molecule’s structure. Orkin’s lab investigates gene regulation of stem cell development, genetic vulnerabilities to cancer and gene and other therapies for treating hemoglobin disorders. 

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BCL11A-based gene therapy for sickle cell disease passes key preclinical test

sickle cell gene therapy coming
(unsplash/Pixabay)

Research going back to the 1980s has shown that sickle cell disease is milder in people whose red blood cells carry a fetal form of hemoglobin. The healthy fetal hemoglobin compensates for the mutated “adult” hemoglobin that makes red blood cells stiffen and assume the classic “sickle” shape.

Normally, fetal hemoglobin production tails off after birth, shut down by a gene called BCL11A. In 2008, researchers Stuart Orkin, MD, and Vijay Sankaran, MD, PhD, at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center showed that suppressing BCL11A could restart fetal hemoglobin production; in 2011, using this approach, they corrected sickle cell disease in mice.

Now, the decades-old discovery is finally nearly ready for human testing — in the form of gene therapy. Today in the Journal of Clinical Investigation, Dana-Farber/Boston Children’s researchers report that a precision-engineered gene therapy vector suppressing BCL11A production overcame a key technical hurdle.

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A long wait, but worth it: Vonvendi’s Boston origins

blood vessel von willebrand factor Vonvendi
(ktsdesign/Shutterstock)

It’s no secret that it can take years, even decades, for a biological or medical discovery to move from the laboratory to the bedside. The Pharmaceutical Researchers and Manufacturers of America estimates that it takes on average at least 10 years (and $2.6 billion) to develop a new medicine from start to market.

But some wait times stand out. Take the story of Vonvendi, a recombinant form of von Willebrand factor (vWF), a clotting protein implicated in von Willebrand disease, a bleeding disorder.

Stuart Orkin, MD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and his then-research fellow David Ginsburg, MD, first cloned the gene for vWF in 1985. Pharmaceutical company Baxalta, which has been developing Vonvendi based on Orkin and Ginsburg’s original discovery, won FDA approval for the drug at the end of 2015.

But what makes this story unique isn’t the 30-year lag. Rather, it’s that — for reasons that aren’t entirely clear — the patent Orkin and Ginsburg filed for vWF in 1985 hung in limbo until 2013. But today, both men agree that while the wait was long, seeing their discovery emerge as a treatment is thrilling to no end.

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Stuart Orkin honored for his lifetime research on blood development

Awards_3
Presenter Bill Evans, IBM Watson Health and Stuart H. Orkin, MD

When colleagues describe Stuart H. Orkin, MD, associate chief of hematology/oncology at Boston Children’s Hospital and chair of pediatric oncology at Dana-Farber Cancer Institute, the words “immeasurable,” “vanguard” and “mentor” quickly roll off the tongue.

In honor of his 35-year career and commitment to blood cell research, Boston Children’s Hospital presented Orkin with the 2015 Lifetime Impact Award, during Boston Children’s Global Pediatric Innovation Summit held this week. The award recognizes a clinician and/or researcher who has significantly impacted pediatric care through practice-changing innovations or discoveries and made extraordinary and sustained leadership contributions in health care throughout his or her career.

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Gene sifting for gene snipping: GWAS as a source of gene editing targets

Magnifying glass people GWAS gene editing
(Digital Storm/Shutterstock)

When genome-wide association studies (GWAS) first started appearing 10 years ago, they were heralded as the answer to connecting human genetic variation to human disease. These kinds of studies—which sift population-level genetic data—have revealed thousands of genetic variations associated with diseases, from age-related macular degeneration to obesity to diabetes.

However, thus far GWAS have largely come up short when it comes to finding new therapies. Few significant drug targets have come to light based on GWAS data (though some studies suggest that these studies could help drug makers find new uses for existing molecules).

Part of the problem may be that, until now, the right tools haven’t been available to exploit GWAS data. But a few recent studies—including two out of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center—have used GWAS data to identify therapeutically promising targets, and then manipulated those targets using the growing arsenal of gene editing methods.

Does this mean that GWAS’ day has finally come?

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