Navigation Links
Potential gene therapy approach to sickle cell disease highlighted at ASH
Date:12/11/2012

BOSTON, Dec. 11, 2012 /PRNewswire-USNewswire/ -- Researchers at Dana-Farber/Children's Hospital Cancer Center (DF/CHCC) have taken the first preliminary steps toward developing a form of gene therapy for sickle cell disease. In an abstract presented on Dec. 10 at the 54th annual meeting of the American Society of Hematology, the research team—led by DF/CHCC's Raffaele Renella, MD, PhD, Stuart H. Orkin, MD, and David A. Williams, MD—announced that they had demonstrated in an animal model the feasibility of activating a form of hemoglobin unaffected by the sickle cell mutation.

The study was included as part of the meeting's Best of ASH session on Dec. 11. At this session, the meeting's scientific co-chairs present what they consider to be the best abstracts of the 4,000-plus presented at the conference.

"This work builds on the transformative basic research discovery of the role of BCL11A in maintaining fetal hemoglobin silencing by the Orkin laboratory with a near-term goal of curing sickle cell disease using gene therapy," said Williams, chief of the Division of Hematology/Oncology at DF/CHCC and senior author on the abstract. "We have had important recent successes in applying this type of gene therapy in treating several other genetic diseases at Boston Children's Hospital."

The team's work builds on previous research, published by Orkin's laboratory, suggesting that strategies targeting a molecular switch called BCL11A have the potential to correct sickle cell disease.

First described over 100 years ago, sickle cell disease (or sickle cell anemia) is an inherited blood disease caused by a single mutation in one of the components of hemoglobin, the oxygen-carrying protein in red blood cells. The mutation reduces the protein's ability to carry oxygen and forces the cells to curve into a distinctive crescent or sickle shape.

Our bodies can actually manufacture two forms of hemoglobin: the adult form susceptible to the sickle cell mutation, and a fetal form that is largely produced during development and for a short time after birth. BCL11A is a transcription factor that facilitates that shift in hemoglobin production. Fetal hemoglobin expression significantly reduces the symptoms and complications of sickle cell disease because it prevents the intracellular abnormalities caused by the sickle mutation.

In their abstract, Renella, Orkin, Williams and their colleagues reported on their efforts to develop a combined lentiviral gene transfer/RNA interference approach capable of turning down BCL11A in vitro in human and mouse cells and in vivo in a mouse bone-marrow transplant model. Among their findings, the researchers documented a five- to 20-fold increase in fetal hemoglobin production in treated mice.

The team is quick to note that they have not yet attempted to correct disease in a model of sickle cell using this approach. Such efforts would be carried out in future studies.

"There are many approaches to sickle cell disease, and while we've shown we can develop viral vectors, knock down BCL11A, and induce fetal hemoglobin production, it's all been done in non-disease model systems," cautioned Renella, a fellow in the Williams laboratory at DF/CHCC. "What we don't yet know is whether we can stop production of sickled cells in a sickle cell system. Further experiments will show us if that is possible."

The study was supported by the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases and the Howard Hughes Medical Institute.

Dana-Farber/Children's Hospital Cancer Center
Since 1947, Boston Children's Hospital and Dana-Farber Cancer Institute have provided comprehensive care for children and adolescents with cancer through Dana-Farber/Children's Hospital Cancer Center. The two Harvard Medical School affiliates share a clinical staff that delivers inpatient care at Boston Children's and outpatient therapies at Dana-Farber's Jimmy Fund Clinic. The Boston Children's inpatient pediatric cancer service has 33 beds, including 13 designated for stem cell transplant patients.

Boston Children's is also the site of DF/CHCC inpatient clinical translational research in pediatric malignancies and has long supported the operation of an effective and productive stem cell transplant service. It has a long history of investment in and support of both clinical and basic cancer research, with more than $7.3 million in National Cancer Institute research support and 47,000 square feet of space devoted to cancer research. It is a recognized center of excellence in angiogenesis, cellular/molecular immunology, cancer genetics, and molecular signaling research.

Contacts:
Rob Graham
Boston Children's Hospital
617-919-3110
Rob.Graham@childrens.harvard.edu

Teresa Herbert
Dana-Farber Cancer Institute
617-632-4090
Teresa_herbert@dfci.harvard.edu


'/>"/>
SOURCE Boston Children's Hospital
Copyright©2012 PR Newswire.
All rights reserved

Related biology news :

1. New coronavirus has many potential hosts, could pass from animals to humans repeatedly
2. ALS TDI and Gladstone Institutes collaborate to discover potential ALS treatments
3. Fracking in Michigan: U-M researchers study potential impact on health, environment, economy
4. Potentially toxic flame retardants found in many US couches
5. Surface analysis techniques for advanced materials enhance Mazovias research potential
6. An international competition reaffirms the potential of bioinformatics in the diagnosis of disease
7. Scripps Research Institute team identifies a potential cause of Parkinsons disease
8. Researchers tap into CO2 storage potential of mine waste
9. Stem cell scientists discover potential way to expand cells for use with patients
10. King Richard III search in new phase after discovery has potential to rewrite history
11. New potential targets discovered for treating squamous cell lung cancers
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:11/15/2016)... 15, 2016  Synthetic Biologics, Inc. (NYSE MKT: ... on the gut microbiome, today announced the pricing ... of its common stock and warrants to purchase ... price to the public of $1.00 per share ... from the offering, excluding the proceeds, if any ...
(Date:6/27/2016)... 2016 Research and Markets has announced the ... report to their offering. The ... to grow at a CAGR of 12.28% during the period ... an in-depth market analysis with inputs from industry experts. The report ... years. The report also includes a discussion of the key vendors ...
(Date:6/21/2016)... Columbia , June 21, 2016 ... to the new role of principal product architect ... named the director of customer development. Both will ... chief technical officer. The moves reflect NuData,s strategic ... in response to high customer demand and customer ...
Breaking Biology News(10 mins):
(Date:11/30/2016)... BILLERICA, Massachusetts , 30. November 2016 ... und Technologieunternehmen, hat heute die Unterzeichnung einer ... gegeben. Diesen zufolge wird Evotec AG Screeningleistungen ... und shRNA-Bibliotheken bereitstellen. Der Zugriff auf diese ... Bereich Screening eröffnet einen schnelleren Weg zur ...
(Date:11/30/2016)... Lafayette, IN (PRWEB) , ... November 30, 2016 , ... ... industry experts to discuss the implications of the latest FDA guidance on pharmaceutical ... December 8, 2016 in Cambridge, MA. , The event follows the successful ...
(Date:11/30/2016)... Triangle Park, North Carolina (PRWEB) , ... November 30, 2016 , ... ... (IUPAC) approved the names and symbols for four elements: nihonium (Nh), moscovium (Mc), ... Following a 5-month period of public review, the names earlier proposed by the discoverers ...
(Date:11/30/2016)... ... November 30, 2016 , ... Microbial genomics leader uBiome ... Arianna Huffington, as part of the Thrive Global pop-up store. This stunning 5,000 ... to explore the microorganisms in their gut, collectively known as the microbiome. , ...
Breaking Biology Technology: