The Paper Was
Written By: Richard O. Snyder, Carol Miao,
Leonard Meuse, Julie Tubb, Brian A Donahue,
Hui-Feng Lin, Darrel W. Stafford, Salil Patel,
Arthur R. Thompson, Timothy Nichols, Marjorie S.
Read, Dwight A Bellinger, Kenneth M. Brinkhous
and Mark A. Kay. The Paper appeared in Nature
Medicine, volume 5, number 1, January
1999.
The ultimate objective of this research is to
develop a new gene therapy protocol for long
term treatment and eventual cure of hemophilia.
The investigators looked at hemophilia B using
small
and large animals as
models.
Previous studies using recombinant retroviruses
resulted in either short-term correction of the
coagulation deficiency or long-term expression
of sub-therapeutic levels, as well as
immunogenecity and toxicity complications. This
study addresses all of these issues and shows
some promising results.
Frequently Asked
Questions
What is hemophilia?
There are two main types of hemophilia, each
with varying degrees of severity. Hemophilia A
is a factor
VIII deficiency; Hemophilia B is
a
factor IX
deficiency. Both are X-linked
recessive disorders. Hemophilia B occurs in
about 1 in 25,000 males.
What are the symptoms of hemophilia and how
is it treated?
Hemophilia causes spontaneous bleeding into
organs, which can be lethal. It can also cause
severe arthritis. Current treatment consists of
transfusion of clotting factors derived from
human blood.
Why the need for a new strategy of
treatment?
There are risks involved with transfusion of
human clotting factors, such as transmission of
HIV or hepatitis viruses.
What was their strategy?
Recombinant AAV vectors were used to
transfect the factor IX gene into hepatocytes,
(liver cells).
Why is the liver significant for gene
therapy in this study?
In other gene therapy studies where the
vector was introduced into the muscle,
antibodies were produced. These investigators
are trying gene transfer via the liver in hopes
that it will not elicit an immune response.
Experiment 1