July 12, 2013
HIV Virus Used To Cure Two Genetic Diseases
[ Watch the Video: Gene Therapy Used By San Raffaele Telethon Institute For Gene Therapy ]
redOrbit Staff & Wire Reports - Your Universe Online
In the studies, Luigi Naldini, director of the San Raffaele Telethon Institute for Gene Therapy (TIGET) in Italy, and his colleagues report they successfully used HIV to cure metachromatic leukodystrophy and Wiskott-Aldrich syndrome in a total of six children, all of whom are reportedly in good health.
"Three years after the start of the clinical trial, the results obtained from the first six patients are very encouraging: the therapy is not only safe, but also effective and able to change the clinical history of these severe diseases," Naldini said in a statement. "After 15 years of effort and our successes in the laboratory, but frustration as well, it's really exciting to be able to give a concrete solution to the first patients."
The idea to use HIV as a potential treatment option for these two genetic diseases first came about in 1996. Both conditions have, at their core, a genetic defect that causes a deficiency in a protein essential for the patient during the early years of his or her life. In metachromatic leukodystrophy, the nervous system is affected and over time children lose cognitive and motor skills, while in Wiskott-Aldrich syndrome, a faulty immune system results, making the child prone to infections, autoimmune diseases and cancer, the researchers explained.
After several years of laboratory study produced positive results, the TIGET researchers attempted to correct the genetic defect that causes these diseases with gene therapy. The technique required to do so involves the withdrawal of hematopoietic stem cells from the patient's bone marrow, then introducing a corrected copy of the gene that is defective using viral vectors derived from HIV. They are then re-injected into the body, allowing the cells to start restoring the missing protein to vital organs.
"In patients with Wiskott-Aldrich syndrome, blood cells are directly affected by the disease and the corrected stem cells replace the diseased cells creating a properly functioning immune system and normal platelets," said study coordinator and Head of Research at TIGER's Pediatric Clinic Alessandro Aiuti. "Thanks to gene therapy, the children no longer have to face severe bleeding and infection. They can run, play and go to school."
"In the case of metachromatic leukodystrophy, however, the therapeutic mechanism is more sophisticated: the corrected hematopoietic cells reach the brain through the blood and release the correct protein that is 'gathered' there by the surrounding nerve cells," added Alessandra Biffi, who led the other study. "The winning card was to make engineered cells able to produce a quantity of protein much higher than normal, and thus effectively counteract the neurodegenerative process."
More than 70 researchers, clinicians and other key team members have been working on the study since the spring of 2010. A total of 16 patients participated, six of whom suffered Wiskott-Aldrich syndrome and the other 10 who had been diagnosed with metachromatic leukodystrophy. The newly-published studies only discuss the results of the first three patients from each trial, as they were the only ones for whom enough time had passed since the administration of the therapy to allow the study authors to draw conclusions regarding its safety and efficacy.
Maria Grazia Roncarolo, scientific director of the San Raffaele Institute and the individual who helped design and lead the Wiskott-Aldrich syndrome trials, said she was "proud" of the results, "both as scientific director and as pediatrician who has dedicated her entire professional life to children affected by genetic diseases.
"These goals are an example of how research conducted with accuracy, determination and total commitment can produce the desired results and lead to new frontiers in medicine. The translational path, from the bench in lab to the bedside of patients affected by Wiskott-Aldrich syndrome and metachromatic leukodystrophy, has also presented obstacles and frustrations, both for researchers and for parents and children who understandably find it hard to accept science 'slowness'. But the results we're showing today repay us of all the efforts and give us a great hope for the future of these children and for the possible cure of other genetic diseases," she added.