In the study, scientists
injected AAV5-hFVIII-SQ, a genetically modified variant of the adeno-associated
virus (AAV) as a slow intravenous infusion over around an hour in nine men with
severe hemophilia A
. The virus was previously modified
to promote the production of factor VIII by the cells of the body, which is
deficient in these patients. One patient was previously taking on-demand factor
VIII injections for hemophilia A, while the others were on preventive
injections. A low and an intermediate dose of the modified virus were
administered in one patient each, while seven patients received high-dose
‘Gene therapy may restore the low factor VIII levels in hemophilia A patients, thereby eliminating the painful bleeding episodes and the need for repeated injections.’
The scientists found
- The factor
VIII activity level improved in all the participants who received
high-dose therapy. The increase in
factor VIII levels was noted between 2 and 9 weeks following the
injection, and stabilized between 20 to 24 weeks. In fact, six out of
seven patients achieved factor VIII levels within the normal range.
Patients with low and intermediate doses had lower than normal levels of
factor VIII (3IU or less), which indicates the dose-related benefit of the
- The level
of factor VIII was sustained even one year after receiving the injection.
- The frequency of bleeding episodes decreased
significantly, as a result of which most patients who received the
high-dose treatment did not require factor VIII injections. The need for
repeated factor VIII injections or pain medications reduced, thereby
improving the quality of life in the patients. Neutralizing antibodies
against factor VIII were not produced in any individual.
- A mild
elevation in the liver enzyme alanine aminotransferase was noted. An increase in aspartate aminotransferase levels was
noted in four patients. Other evidences of possible liver
damage were not noted.
- One patient developed progression of previous chronic
joint disease. Other mild adverse effects noted included joint disease,
back pain, fatigue and productive cough, which may or may not have been
associated with the treatment.
four participants showed high levels of factor VIII intermittently, there
were no adverse episodes of excessive clotting like stroke or heart
attack These patients
had normal levels of platelet count, prothrombin time, and activated
partial-thromboplastin time, which are indicative of normal bleeding and
The study thus stresses
on the potential of gene therapy to improve the life of patients with
hemophilia A and eliminate the need for regular injections. Further studies in
larger number of patients are required to establish the efficacy and detect any
adverse effects of this novel approach of treating hemophilia A.
A is a genetic disorder where the patient lacks a protein in the blood called
A deficiency of the protein makes the patient bleed easily
on exposure to trauma, or even spontaneously in severe cases. Bleeding into the
joints can result in painful joint swelling and arthritis. Uncontrolled bleeds
in the brain and other parts of the body can be fatal. The condition
predominantly affects males while females tend to be carriers.
Hemophilia A patients
are treated with replacement of factor VIII either on an as-and-when needed
basis to heal a bleeding episode or as a preventive treatment on a regular basis.
Preventive treatment with factor VIII has some disadvantages-it needs to be
injected up to 3 times weekly, and the patient can still suffer from bleeding
episodes at times when the factor VIII level is low.
- Rangarajan S et al. AAV5-Factor VIII Gene Transfer in Severe Hemophilia A. New England Journal of Medicine (2017); DOI: 10.1056/NEJMoa1708483