FYI from the NHLBI Index

January 2007: Vol. 7, Issue 3
In the News

Improving Gene Therapy for People Who Have Hemophilia A
Registry Leads to Better Clinical Care
Losartan May Prevent Aortic Aneurysms

News from Capitol Hill

Continuing Resolution for Fiscal Year (FY) 2007 Appropriations

The Congress passed a continuing resolution (H.J.R. 102) on December 8, 2006, as a short-term measure to continue funding for the NIH at the FY 2006 level. The President signed the resolution into law on December 9, 2006 (P.L. 109-383). The new continuing resolution, which will expire on February 15, 2007, is the third temporary funding resolution passed by the Congress for the 2007 fiscal year, which began on October 1, 2006.

The National Institutes of Health Reform Act of 2006

On December 8, 2006 the Congress passed the National Institutes of Health Reform Act of 2006 (H.R. 6164) to reauthorize the NIH. If signed into law by the President, the measure would create a new Division of Program Coordination, Planning, and Strategic Initiatives within the office of the NIH Director to coordinate trans-NIH activities and develop trans-NIH initiatives. The new law would provide the first reauthorization of NIH since 1993.

Modified 1/31/07
[Back to Top]
[Table of Contents]

Recent Advances from the NHLBI

Improving Gene Therapy for People Who Have Hemophilia A

A new gene therapy technique holds promise for some hemophilia patients who have lost the ability to benefit from standard treatment. People who have hemophilia A lack a functional form of factor VIII, a protein that enables the blood to clot in response to injury. Although infusions of replacement protein are effective, 20 to 30 percent of patients eventually develop antibodies that inhibit the protein’s clotting activity and render subsequent infusions ineffective. Gene therapy has been viewed as a promising treatment for hemophilia, but most gene therapy strategies that are being pursued use liver cells to produce factor VIII protein. Such an approach would not benefit patients with inhibitory antibodies because the liver-produced factor VIII protein would be inactivated before it reached the site of injury.

However, researchers have now developed a strategy for expressing the factor VIII gene in blood platelets instead of in the liver. Because circulating platelets home to the site of injury before releasing their contents, they could deliver factor VIII protein directly to where it is needed for clotting. Using a mouse model of hemophilia A, researchers demonstrated that platelet-produced factor VIII protein stopped bleeding even in mice with circulating inhibitory antibodies. Although much more work is needed before gene therapy is offered as a realistic treatment for hemophilia patients, the latest finding indicates that continued research in this area might benefit more patients than previously thought.

Registry Leads to Better Clinical Care

Data collected from the 420 participants in the Diamond-Blackfan anemia (DBA) registry have prompted some physicians to change how they treat patients who have DBA.

Although corticosteroids and blood transfusions continue to be the standard therapies for DBA patients, the registry has documented that corticosteroids are likely to cause serious side effects when given to children in the first year of life.

Data from the registry also reveal that more infants are receiving blood transfusions as a first line of treatment, presumably because physicians who care for DBA patients are becoming more cognizant of the risks posed by corticosteroids.

The registry also has led to a new understanding of which patients could benefit from a bone marrow or cord blood transplant.

Because registry participants who received cells from unrelated or mismatched donors were at a higher-than-expected risk of death but those who had a matched sibling donor fared particularly well, investigators are not recommending that DBA patients receive bone marrow or cord blood transplants unless the cells are donated by a well-matched brother or sister.

Losartan May Prevent Aortic Aneurysms

New research offers hope that losartan, a drug commonly prescribed to treat hypertension, might also be used to treat Marfan syndrome, a genetic disorder that often causes life-threatening aortic aneurysms. After the discovery that Marfan syndrome is associated with a mutation in the gene encoding fibrillin-1, researchers tried for many years, without success, to develop treatment strategies that involved repair or replacement of fibrillin-1.

Recently, a major breakthrough occurred with the discovery that one of the functions of fibrillin-1 is to bind to another protein, TGF-beta, and regulate its effects. After careful analyses revealed aberrant TGF-beta activity in patients with Marfan syndrome, researchers began to concentrate on treating Marfan syndrome by normalizing the activity of TGF-beta.

Losartan, which is known to affect TGF-beta activity, was tested in a mouse model of Marfan syndrome. The results showed that the drug blocked the development of aortic aneurysms as well as lung defects associated with the disease. Based on the promising results of the study, the NHLBI Pediatric Heart Network is undertaking a trial of losartan in patients with Marfan syndrome. The effects of losartan on other diseases known to involve abnormal TGF-beta activity are also being explored.