Gene Therapy for Rare Immune System Disease Shows Promise

Wiskott-Aldrich treatment shows robust clinical effect.

Wiskott-Aldrich treatment shows robust clinical effect.

An experimental gene therapy for the treatment of a rare disease that affects the immune system showed significant promise during a recent clinical study.

Wiskott-Aldrich syndrome (WAS) is a congenital immune and platelet deficiency caused by mutations in the gene that encodes the WAS protein (WASp) expressed in hematopoietic cells. The disease causes bleeding, severe and recurrent infections, severe eczema, and in some cases can cause autoimmune reactions and cancer.

The only current treatment available for WAS, which primarily affects boys with an estimated prevalence of 1 in 250,000, is a bone marrow transplant.

The ongoing study, published in JAMA, reported the feasibility and efficacy of gene therapy for WAS in 6 children who were treated and followed for at least 9 months. The study, found the patients had their immune system restored and showed an improvement in their clinical condition.

"This is a very powerful example of how gene therapy can offer highly effective treatment for patients with complex and serious genetic disease,” study lead Adrian Thrasher said in a press release. “It also excitingly demonstrates the potential for treatment of a large number of other diseases for which existing therapies are either unsatisfactory or unavailable."

The gene therapy involved collecting blood stem cells that carry a genetic anomaly to correct it in the laboratory setting. This correction involves the introduction of a healthy WAS gene utilizing a lentiviral vector.

The corrected cells were subsequently injected back into the patients, who were concurrently treated with chemotherapy to suppress defective stem cells and autoimmune cells in order to make room for the newly corrected cells. After the injection, the new cells were differentiated into various cell lines that comprise red and white blood cells and platelets.

"The results obtained in this multicenter clinical trial constitute an important therapeutic advance because they concern a complex pathology which affects almost all of blood cells with dramatic clinical consequences,” researcher Marina Cavazzana said in a press release. “After transfer of gene, the patients showed a significant clinical improvement due to the re-expression of the protein WASp in the cells of the immune system. The efficiency of the treatment of such a deficit for which a high level of correction of hematopoietic stem cells is required, indicates that it is from now on justifiable to hope to treat other complex genetic diseases as those affecting red blood cells."

Thus far, the patients treated with the therapy have shown significant clinical improvement, including the disappearance of severe eczema and severe infection in all cases.

Arthritis was eliminated in one patient, while another patient experienced a major improvement in vasculitis of the lower limbs.This allowed the patient to resume normal physical activity without the use of a wheelchair.

The study also found that the rate of corrected platelets differed from one patient to another.

"We are all very happy and encouraged by the results of this study. It is the first time that a gene therapy based on genetically modified stem cells is tested in a multicenter, international clinical trial that shows a reproducible and robust therapeutic effect in different centers and different countries,” Fulvio Mavilio, chief scientific officer at Genethon said in a press release. “For very rare diseases such as WAS, multicenter clinical trials are the only effective way of proving the safety and efficacy of gene therapy and having it rapidly approved and made available to all patients. We are following the same approach for other rare and less rare blood diseases."