JCI online early table of contents: April 8, 2008

Jiahuai Han

The Scripps Research Institute, La Jolla, California, USA.

Phone: (858) 784-8704; Fax: (858) 784-8665; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33680

HEMATOLOGY

Too much of a good thing: high levels of factor VIIa cause problems in mice

Individuals with hemophilia lack either factor VIII or factor IX, proteins crucial for the cascade of events that leads to blood clotting. Although individuals with hemophilia can be treated by intravenous infusion of the factor that they miss, over time, some individuals develop antibodies that prevent the infused factor from working. Intravenous infusion of an activated form of a factor that works earlier in the blood clotting cascade, factor VII (FVIIa), has been used for over a decade to treat individuals who develop antibodies that target factor VIII or factor IX. However, some researchers and clinicians hope that FVIIa gene therapy might provide a simplified way to provide FVIIa to individuals with hemophilia. In a new study, Katherine High and colleagues, at The Children’s Hospital of Philadelphia, have determined a safe and effective level of mouse FVIIa that can be continuously expressed in hemophilia B mice through gene therapy.

The authors observed that continuous expression for up to 16 months of up to 1.5 micrograms per milliliter of mouse FVIIa, either by engineering hemophilia B mice to express this factor throughout life or by treating hemophilia B mice with gene therapy, was safe and corrected the abnormal bleeding of the mice. By contrast, continuous expression of 2 micrograms per milliliter (or more) of mouse FVIIa was associated with early mortality and with heart and lung problems. These data should provide useful information for researchers and clinicians developing gene therapy approaches for the treatment of individuals with hemophilia.

TITLE: Long-term expression of murine activated factor VII is safe, but elevated levels cause premature mortality

AUTHOR CONTACT:

Katherine A. High

The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Phone: (215) 590-4521; Fax: (215) 590-3660; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=32878

VIROLOGY

A pox on TLR9: the immune molecule TLR9 is crucial to prevent lethal poxvirus infection in mice

Smallpox is caused by infection with variola virus, a member of a family of viruses known as poxviruses. New data, generated by Hubertus Hochrein and colleagues, at Bavarian Nordic GmbH, Germany, have identified the protein TLR9 as central to immune defense against infection with some poxviruses in mice.