|
Researchers from
the United
Kingdom (UK) and
the U.S. have
made a
breakthrough in
hemophilia gene
therapy. In a
study published
last month, the
team reported
successfully
treating six
patients with
severe
hemophilia B.
The lead author
of the study was
Amit C. Nathwani,
MB, ChB, PhD,
Department of
Hematology,
University
College London
(UCL) Cancer
Institute,
London.
The UCL
investigators
used adeno-associated
viruses (AAVs)
as delivery
vehicles, or
vectors, to
carry the
genetic codes
that trigger the
production of
the factor IX
(FIX) protein,
which is
deficient in
hemophilia B
patients.
Ideally, AAVs
deliver the
genetic material
into living
cells to sustain
therapeutic
effect without
causing disease
or triggering
significant
immune
responses.
Nathwani
and his team
reported that a
single injection
of the gene
therapy into an
arm vein
activated the
production of
small amounts of
FIX--enough to
allow four
patients to stop
using FIX
concentrates.
The other two
patients needed
fewer factor
concentrate
infusions. Their
factor levels
went from less
than 1% before
the trial to a
range of 2%-12%,
which is
significant. The
patients have
continued to
produce their
own FIX for up
to 22 months.
The liver
enzymes of two
patients were
elevated, but
were
successfully
treated with
steroids.
Despite
moderate
successes, the
field of gene
therapy has
faced some major
challenges and
setbacks during
the last couple
of decades.
Following the
1999 death of
Jessie Gelsinger,
an 18-year-old
patient with a
rare metabolic
genetic disorder
enrolled in a
gene therapy
trial at the
University of
Pennsylvania,
clinical studies
nationwide were
stopped and
investigators
re-evaluated the
therapy.
During the last
decade, one of
the major
focuses for
researchers has
been on
developing
optimal AAVs.
These viruses
are often
favored because
patients have
little or no
immunity
to them and they
do not cause
disease.
Further, AAVs
often target
liver cells,
which
manufacture FIX.
One potential
drawback,
however, is
long-term
viability. Liver
cells have a
finite life span
and are slow to
regenerate,
which may affect
the duration of
the therapy.
The AAVs for
this study were
prepared by a
team from the
St. Jude
Children’s
Research
Hospital
in Memphis, TN.
The patients
were recruited
and treated with
the therapy by
investigators at
UCL. Study
co-author
Katherine High,
MD, and fellow
researchers at
the
Children’s
Hospital of
Philadelphia,
are monitoring
the patients for
any immune
reactions.
High’s
laboratory has
been conducting
gene therapy
clinical trials
for hemophilia
for more than a
decade.
According to
Edward G.D.
Tuddenham, MB,
BS, MD, director
of the
Hemophilia
Center
at the Royal
Free Hospital in
London, 20
additional
patients will
receive the
therapy to help
determine the
optimal dose of
the AAV. The aim
is to deliver
the highest
possible dose
while
circumventing an
unwanted immune
response. “We
are pretty close
to the sweet
spot,” explained
Tuddenham. “If
all goes well, a
genetic
treatment for
hemophilia B
could be
available for
widespread use
in a couple of
years.”
However, it
should be noted
that the
breakthrough
therapy was
tested on a very
small number of
subjects. It
will need to be
repeated in
clinical trials
at other
institutions on
larger numbers
of patients.
The study,
“Adenovirus-Associated
Virus
Vector–Mediated
Gene Transfer in
Hemophilia B,”
was published
online on
December 10,
2011, by
The New England
Journal of
Medicine.
Source:
The New York
Times,
December 10,
2011
|