New approach to sickle-cell disease shows promise in mice

Dec 07, 2009

A new genetic approach to treating sickle cell disease is showing promising results in mice, report researchers from Children's Hospital Boston. By inactivating a gene they previously discovered to be important in the laboratory, they were able to boost production of a healthy fetal form of hemoglobin in the mice, potentially compensating for the defective adult hemoglobin that causes red blood cells to "sickle" and obstruct blood flow.

The study was presented by first author Jian Xu, PhD, on Sunday, December 6, at the American Society for Hematology meeting in New Orleans.

Currently, there are only a limited number of therapies available for patients with , the most common inherited in the U.S., says senior study author Stuart H. Orkin, MD, of Children's Division of Hematology/Oncology, also David G. Nathan Professor of Pediatrics at Harvard Medical School.

Shortly after birth, babies switch from producing the fetal form of , the protein inside red that carries oxygen, to producing the adult form - the type that is affected in sickle cell disease. It's long been known that people who retain the ability to produce have much milder disease. In previous studies, the Children's researchers, with collaborators, found that a gene called BCL11A is involved in switching off fetal hemoglobin production in adults. Working with genetically engineered mice, they then explored whether that switch could be turned back on to alleviate the disease.

In embryonic mice, inactivation of the BCL11A gene led to a robust expression of gamma-globin (the long protein chains making up the fetal form of hemoglobin) during late gestation: more than 90 percent of the globin produced was of this fetal type. In adult mice (8-10 weeks old), inactivation of the BCL11A gene in the resulted in more than a 1,000-fold increase in gamma-globin production in bone marrow erythroblasts (the precursors to ) as compared with control mice. This increase was rapid and persisted during the course of the experiments (up until the mice were 25 weeks old).

This line of research began with comprehensive gene association studies, published in 2008 with collaborators at the Broad Institute of Harvard and MIT. These studies, involving 1600 patients with sickle cell disease, identified five DNA sequence variants (altered strings of genetic code) that correlated with fetal hemoglobin levels. BCL11A, on chromosome 2, had the largest effect, and Orkin and Vijay Sankaran, an MD-PhD student working with Orkin, later demonstrated that this gene directly suppresses fetal hemoglobin production.

If these preliminary results in mice hold up in human studies, inactivating BCL11A may also help patients with thalassemia, another blood disorder involving abnormal hemoglobin, adds Orkin.

Source: Children's Hospital Boston (news : web)

Explore further: Restrictions lifted at British bird flu farm

add to favorites email to friend print save as pdf

Related Stories

Gaining ground on sickle cell disease

Jul 15, 2008

Although sickle cell disease is a single-gene disorder, its symptoms are highly variable. In a study published online July 14 by the Proceedings of the National Academy of Sciences, scientists at Children's Hospital Boston ...

Recommended for you

Restrictions lifted at British bird flu farm

9 hours ago

Britain on Sunday lifted all restrictions at a duck farm in northern England after last month's outbreak of H5N8 bird flu, the same strain seen in recent cases across Europe.

Recorded Ebola deaths top 7,000

Dec 20, 2014

The worst Ebola outbreak on record has now killed more than 7,000 people, with many of the latest deaths reported in Sierra Leone, the World Health Organization said as United Nations Secretary-General Ban ...

Liberia holds Senate vote amid Ebola fears (Update)

Dec 20, 2014

Health workers manned polling stations across Liberia on Saturday as voters cast their ballots in a twice-delayed Senate election that has been criticized for its potential to spread the deadly Ebola disease.

Evidence-based recs issued for systemic care in psoriasis

Dec 19, 2014

(HealthDay)—For appropriately selected patients with psoriasis, combining biologics with other systemic treatments, including phototherapy, oral medications, or other biologic, may result in greater efficacy ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.