Even at a place like Boston Children’s Hospital, where doctors regularly see children with rare diseases from all over the world, there are big challenges when it comes to drug discovery and treatment.
“Roughly 70 percent of drugs to treat children are used off-label,” says David Williams, Boston Children’s chief scientific officer. “That’s because these drugs were initially developed for adults and have not been tested formally in children.”
In order to cure rare diseases in children and adults, scientists must bridge the gap between research and industry. On May 25, Boston Children’s Technology and Innovation Development Office (TIDO) and MassBio held a candid panel discussion about what it will take to advance the development of rare disease therapies. Here are three of the biggest takeaways …
Gene therapy stalled in the early 2000s as adverse effects came to light in European trials (leukemias triggered by the gene delivery vector) and following the 1999 death of U.S. patient Jesse Gelsinger. But after 30 years of development, and with the advent of safer vectors, gene therapy is becoming a clinical reality. It falls into two main categories:
In vivo: Direct injection of the gene therapy vector, carrying the desired gene, into the bloodstream or target organ.
Ex vivo: Removal of a patient’s cells, treating the cells with gene therapy, and reinfusing them back into the patient, as in hematopoietic stem cell transplant and CAR T-cell therapy.
When Boston Children’s Hospital decided to hire its first chief scientific officer (CSO) in eight years, the institution sought an individual who could spotlight the hospital’s robust scientific enterprise and effectively connect it to clinical medicine and industry. David Williams, MD, president of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and director of clinical and translational research at Boston Children’s, was the ideal choice.
An award-winning researcher, Williams trained in the clinic but also pursued basic science, developing techniques for introducing genes into mouse and human blood cells. He focused on blood stem cell biology, leukemia and gene therapy to correct genetic blood disorders, becoming a 16-year Howard Hughes Medical Institute Investigator, a Member of the National Academy of Medicine and a Fellow of the American Association for the Advancement of Science. He has secured multiple patents for techniques still in use today.
Williams spoke about his vision as CSO to align basic research and clinical care at Boston Children’s and the challenges ahead. …
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. …
When Brenden Whittaker of Columbus, Ohio, the first patient treated with gene therapy for chronic granulomatous disease (CGD), showed successful engraftment last winter, the gene therapy team lifted glasses for a celebratory toast. The wine they sipped was no ordinary wine. The 2012 Bordeaux blend came from an award-winning California vineyard owned and operated by Robert Baehner, MD, a pioneering pediatric hematologist with ties to Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.
Decades before, Baehner had done fundamental research in CGD, an inherited immune system disorder that occurs when phagocytes, white blood cells that normally help the body fight infection, cannot kill the germs they ingest and thus cannot protect the body from bacterial and fungal infections.
Children with CGD are often healthy at birth, but develop severe infections in infancy and early childhood from bacteria that would cause mild disease or no illness at all in a healthy child. This was true for Whittaker. Diagnosed with CGD when he was 1, his disease became increasingly severe, forcing him to quit school several years ago. …
Although there are more than 150 types of childhood cancer, pediatric cancer receives only a small fraction of NIH and National Cancer Institute funding, Williams writes. Yet, he points out, just as breakthroughs in adult cancer research can help children, breakthroughs in pediatric cancer can also benefit adults.
Williams and other members of the Coalition for Pediatric Medical Research recently met with the staff of Vice President Joseph Biden, leader of the federal government’s cancer moonshot. Their message? Make sure that pediatric cancer is represented on the moonshot.