Boston Children’s Hospital to receive $1.5M to initiate basic work to expand gene therapy treatment of sickle cell disease into developing countries
December 19, 2018
focus on adapting gene therapy for use in low-resource areas with high rates of
Boston Children’s Hospital will receive a $1.5 million grant from the Bill & Melinda Gates Foundation to develop more efficient gene therapy treatments for sickle cell disease and methods that will enable gene therapy to be used in developing regions of the world with high rates of sickle cell disease.
gene therapies are currently confined to a few research hospitals in the U.S.
and other developed countries, our long-term goal is to make this treatment
available to patients in developing countries — and we have already begun to
think about how to translate this specialized, potentially curative therapy,”
says David A. Williams, MD, chief
scientific officer and senior vice president of Boston Children's Hospital and
President of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, who
will lead the collaborative project with Drs. Paula Hammond of the Koch
Institute, Christian Brendel of Dana-Farber/Boston Children’s, Harvey Lodish of
the Whitehead Institute, and David Scadden at Massachusetts General Hospital.
therapy delivers genetic material into a patient’s cells to replace faulty or
missing genes — or adds new genes — in an attempt to cure diseases or to make
changes so the body is better able to fight off disease. In particular,
Williams hopes to adapt methods used in the current Dana-Farber/Boston
Children’s gene therapy clinical trial for sickle cell disease, which
suppresses a gene called BCL11A, enabling patients to make a fetal, non-sickling form of hemoglobin.
several other gene therapy trials for sickle cell disease, this form of gene
therapy is ex vivo — meaning it
involves removing blood stem cells from the body, treating them with a gene
therapy vector, and then infusing the cells back into the patient. However, ex vivo gene therapy involves multiple complicated
manufacturing steps, takes weeks to complete and requires significant
hospitalization. In contrast, in vivo
gene therapy involves direct injection of the gene therapy vector, carrying the desired gene,
into the bloodstream or target organ. The goal of this work is to develop
methods that allow in vivo gene
therapy applications for sickle cell disease in areas of the world where health
care is less developed than in the United States and Europe.
an in vivo approach, in which a gene
or inhibitory RNA is delivered directly to the body, is likely to be optimal
for broadening global access to gene therapy for sickle cell disease,” says
Williams. “Our vision is to apply our expertise in bioengineering and vector
technology, hematology and stem cell engraftment with minimal marrow
conditioning, and closed and simplified manufacturing to ‘commoditize’ gene
disease is a major public health concern in the developing world, leading to
high rates of mortality and life-long morbidities. An estimated 275,000 infants
are born annually with sickle cell disease worldwide, with more than half of
those in developing countries dying in early childhood. At the same time, the
global cost of sickle cell disease is increasing as fewer children die from
infectious diseases with the broadened use of prophylactic antibiotics in
children with this disease. The impact of the disease is greatest in
sub-Saharan Africa and India. It is estimated that in the U.S., more than $1
billion per year is spent on care of individuals with sickle cell disease.
the grant, Williams and colleagues will conduct research in gene delivery
methods to solve current bioengineering and manufacturing constraints.
look at new technologies of non-viral methods for introducing the therapeutic
gene into stem cells that could help standardize gene therapies and make them
more available and affordable,” says Williams.
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