HIV Virus Used As Vector To Get Gene Therapy Into Six Children

The HIV Virus can be used to treat two severe genetic diseases, according to two studies published in the journal Science.

Researchers from the San Raffaele Telethon Institute for Gene Therapy (TIGET) in Milan, Italy, have revealed that the HIV virus can be used to treat metachromatic leukodystrophy, a disease impairing the fatty covering that acts as an insulator around nerve fibers and Wiskott-Aldrich Syndrome, an immune system deficiency reducing the ability to form blood clots.

The researchers say that the origin of both these diseases is a genetic defect that results in the deficiency of a protein essential in the early years of life. The HIV therapy technique, called lentiviral hematopietic stem cell gene therapy, involves withdrawing hematopoietic stem cells – cells isolated from the bone marrow that can renew themselves – from the bone marrow of the patients.

The patients are then given a corrected copy of the defected gene using viral vectors derived from HIV. A viral vector is a tool that enables the transfer of genetic material into cells. Once this process is complete, the treated cells are able to restore the missing proteins to the key organs, researchers say.

The results of the study revealed that six children from all over the world have received this treatment over the last three years, and are “well and show significant benefits.”

Alessandro Aiuti, head of research of the pediatric clinic at TIGET, explains:

“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. 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. 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.”

Luigi Naldini, the leader of this study, adds: “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. It’s really exciting to be able to give a concrete solution to the first patients.”

Both trials for this treatment began with 16 participants in 2012. Six of the patients were suffering from Wiskott-Aldrich Syndrome and 10 were suffering from metachromatic leukodystrophy. However, the published results refer to six of the patients for whom sufficient time has passed after administration of the therapy.

Maria Grazia Roncarolo, scientific director of TIGET, says: “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.”