In a world first, Australian researchers at Royal Prince Alfred Hospital have established how to deliver gene therapy successfully and safely.
As part of an international clinical trial, the Australian scientists have effectively achieved a gene transfer in the liver of men with hemophilia, offering a potential cure for this debilitating disease and hope for the future treatment of many other diseases.
Gene therapy is an approach to treating disease by either modifying the expressions of an individual’s genes or correcting abnormal genes, in this case by introducing a missing gene transported to the patient’s liver encased in a harmless virus.
Advances in the field of gene therapy have been limited by severe side effects, failure to deliver sufficient genes and lack of gene function in the recipient’s body.
In an additional step forward, the researchers predict that if they suppress the immune system for several months, the patient’s body will allow the gene to become established, providing a long-term cure.
The study, a collaboration between researchers in Australia, USA and South America, is published in the current edition of the internationally acclaimed leading medical journal Nature Medicine.
Lead Australian researcher Professor John Rasko said the study was designed to demonstrate the safety and necessary dosage required to produce a life-long cure for hemophilia, a bleeding disorder in which one of the essential clotting factors is deficient.
“This is the first time a healthy gene has been successfully introduced directly into the body of a person, in this case suffering from hemophilia, with a sustained result,” Prof Rasko said.
“In two patients we were able to show that the gene encoding the factor they lack at birth could be delivered to the liver following a single injection. This gene converted their own livers into a factory for this essential clotting protein in the fight against the disease,” said Prof Rasko.
Seven hemophilic men were treated with the healthy clotting factor gene carried by a virus, which was introduced into their liver via a catheter. The therapeutic gene was encoded in a harmless virus called AAV which approximately two thirds of people have been exposed to in childhood.
This showed that gene therapy could be safely delivered to the liver at a level sufficient to convert the person with severe hemophilia to one with only a mild predisposition to bleeding.
But after about one month of sustained production of the clotting factor in the liver, a gradual decline occurred, returning to baseline levels ten weeks after gene therapy.
Prof Rasko said that painstaking laboratory studies revealed that the patient’s own immune cells were attacking the therapeutic virus which was coating the cells producing the essential clotting factor.
They predict that if they suppress the immune system for several months, the patient’s body will not attack the virus transporting the gene, allowing the gene to become established in the liver providing a lifelong cure.
It would be expected that at the end of the immune suppression, all trace of the virus would have disappeared. By that time, the gene would be established in the body and able to provide long-term results.
“Progress in this field provides hope, not only for those suffering from hemophilia, but as proof-of-principle for the future treatment of any one of thousands of genetic disorders such as cancer, diabetes, thalassemia and heart disease,” said Prof Rasko.
“This is really a platform technology which could provide cures for many severe diseases. The potential is enormous,” said Prof Rasko.
Researchers plan to establish a new trial to confirm the findings.
It is estimated that more than 1,800 people in Australia are afflicted with hemophilia. Most sufferers are male and hemophilia is a hereditary life-long condition. The clinical severity of the condition is related to the level of deficiency of the clotting factor.
This media release and photographs are available at www.sswahs.nsw.gov.au
Issued by Sydney South West Area Health Service Public Affairs. For further information contact Melissa Roberts or Rebecca Murray on (02) 9515 9607
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