Gene therapy: success in the treatment of hereditary disease
A group of researchers from France and the UK demonstrated the effectiveness of the experimental method of gene therapy in the treatment of a rare hereditary disease – Wiskott-Aldrich syndrome.
This X-linked disease occurs with a frequency of 1 case per 250,000 people and is caused by mutations of the gene encoding the WAS protein expressed by hematopoietic stem cells. Predominantly affecting boys, the disease is characterized by severe insufficiency of the immune system and platelet growth of blood, which is manifested by bleeding, severe recurrent infections, severe forms of eczema, as well as the development of autoimmune reactions and cancer in some patients. To date, the only effective treatment for Wiskott-Aldrich syndrome is bone marrow transplantation, which requires a compatible donor and is associated with a number of life-threatening complications.
The ongoing Phase I/II clinical trial initiated by Genethon was launched in December 2010. To date, 6 patients aged 8 months to 16 years who do not have compatible donors for bone marrow transplantation have already participated in it.
Experimental therapy consists in isolating the patient's hematopoietic stem cells carrying a genetic anomaly and correcting them by introducing a normal WAS gene using a lentiviral carrier vector. After that, the modified cells are injected back to the patient who has previously undergone a course of chemotherapy that suppresses the activity of his defective hematopoietic and autoimmune cells. After introduction into the body, modified cells take the place of defective stem cells weakened by chemotherapy, begin to actively multiply and differentiate, giving rise to all types of blood cells: erythrocytes, leukocytes and platelets.
To date, all study participants whose condition has been monitored for at least 9 months have experienced a significant decrease in the severity of symptoms of the disease. In all cases, the manifestations of eczema and severe infections disappeared. In one patient, the symptoms of arthritis disappeared, and in another, the manifestations of vasculitis of the lower extremities significantly decreased, which allowed him to abandon the wheelchair and return to normal physical activity. At the same time, the degree of normalization of platelet levels in the blood varies significantly from patient to patient.
The researchers believe that the preliminary results obtained indicate that gene therapy can be an effective method of treating complex and severe genetic diseases. They also point to the possibility of using gene therapy in the fight against various diseases that currently have no effective treatment methods.
Article by Salima Hacein-Bey Abina et al. Outcomes Following Gene Therapy in Patients With Severe Wiskott-Aldrich Syndrome is published in the Journal of the American Medical Association.