Gene therapy shown to assist
blood clotting in haemophilia
An experimental gene therapy technique
boosted the production of a vital blood
clotting factor in six people with
haemophilia B, according to new research
published online 10 December 2011 in the
New England Journal of Medicine. The
therapy could give patients a long-term
solution for preventing prolonged bleeding
episodes and spontaneous bleeding.
Haemophilia B patients are unable to
produce enough human clotting factor IX,
also referred to as FIX, which is essential
for normal blood clotting. Liver cells are
the only cells in the body capable of
producing a form of factor IX that is active
in the clotting process.
In the study researchers joined the FIX
gene to a virus that targets liver cells. This
allowed the normal FIX gene to be delivered
using intravenous infusion to the liver
cells of patients with haemophilia B. The
infusion allowed the patients to produce
Researchers from the University College
London Cancer Institute, and St. Jude
Children’s Research Hospital, Memphis,
in the US, led a team that examined the effects of delivering the FIX gene to
patients. Scientists inserted the FIX gene
into a virus, which served as the delivery
vehicle for the gene therapy.
The researchers studied six people with
severe haemophilia B who were producing
clotting factor IX at less than 1% of normal
levels before receiving the gene therapy.
Prior to enrolling in the study, participants
were receiving the standard treatment for
severe haemophilia B of infusions of manufactured
FIX several times a month.
The FIX gene was packaged in a modified adeno-associated virus, AAV8, which
targets liver cells. After receiving the FIX
gene therapy, each participant produced
FIX at between 2% and 11% of normal
levels. In the short-term follow-up period
(six to 16 months), four of the six participants
no longer required FIX infusions for
routine bleeding. The other two participants
required FIX infusions less frequently
than before the study.
The unique feature of this approach is
the use of AAV8 to deliver the gene to the
appropriate cells. If future studies show
that immunologic or other factors do not limit its long-term effectiveness,
with haemophilia B could produce their
own FIX and potentially avoid reliance
upon FIX infusions. While more work is
needed, these results are more promising
than prior attempts at gene therapy for the
Haemophilia B is less common than
haemophilia A, a deficiency of clotting
factor VIII. About 1 in 5 haemophilia
patients has haemophilia B, while the
other four have haemophilia A.
Haemophilia is an inherited condition
that affects men more frequently.
Worldwide, about 1 in 5,000 men are born
with haemophilia A and 1 in 25,000 men
are born with haemophilia B each year.
Organisations in the United Kingdom
that provided funding for this research
included: the National Health Service; the
National Institute for Health Research; the
Department of Health; and the Royal Free
Hospital. Funding sources in the United
States included: the Howard Hughes
Medical Institute; the ASSISI Foundation
of Memphis; and the American Lebanese
Syrian Associated Charities.
of upload: 21st Jan 2012