Photo by Chad McNeeley
Results of a small study suggest gene therapy can lead to clinical improvements in children and teens with Wiskott-Aldrich syndrome (WAS).
The gene therapy—autologous, gene-corrected hematopoietic stem cells (HSCs) given along with chemotherapy—improved infectious complications, severe eczema, and symptoms of autoimmunity in 6 of the 7 patients studied.
The therapy also reduced patients’ use of blood products and the amount of time they spent in the hospital.
Marina Cavazzana, MD, PhD, of Necker Children’s Hospital in Paris, France, and colleagues reported these results in JAMA. The study was sponsored by Genethon.
The researchers noted that WAS is caused by loss-of-function mutations in the WAS gene. The condition is characterized by thrombocytopenia, eczema, and recurring infections. In the absence of definitive treatment, patients with classic WAS generally do not survive beyond their second or third decade of life.
Partially HLA-matched, allogeneic HSC transplant is often curative, but it is associated with a high incidence of complications. Dr Cavazzana and colleagues speculated that transplanting autologous, gene-corrected HSCs may be an effective and potentially safer alternative.
So the team assessed the outcomes and safety of autologous HSC gene therapy in 7 patients (age range, 0.8-15.5 years) with severe WAS who lacked HLA antigen-matched related or unrelated HSC donors.
Patients were enrolled in France and England and treated between December 2010 and January 2014. Follow-up ranged from 9 months to 42 months.
The treatment involved collecting mutated HSCs from patients and correcting the cells in the lab by introducing a healthy WAS gene using a lentiviral vector developed and produced by Genethon. The corrected cells were reinjected into patients who, in parallel, received chemotherapy to suppress their defective stem cells and autoimmune cells to make room for new, corrected cells.
Six of the 7 patients saw clinical improvements after this treatment. One patient died of pre-existing, treatment-refractory infectious disease.
In the 6 surviving patients, infectious complications resolved after gene therapy, and prophylactic antibiotic therapy was successfully discontinued in 3 cases. Severe eczema resolved in all affected patients, as did signs and symptoms of autoimmunity.
There were no severe bleeding episodes after treatment. And, at last follow-up, none of the 6 surviving patients required blood product support.
The median number of hospitalization days decreased from 25 during the 2 years before treatment to 0 during the 2 years after treatment.
“[T]he patients showed a significant clinical improvement due to the re-expression of the protein WASp in the cells of the immune system,” Dr
Cavazzana said.
However, the researchers also noted that the interpretation of these results is constrained by the small number of patients studied. So the team said they could not draw conclusions on long-term outcomes and safety without further follow-up and additional trials.
