Refinements in gene therapy prove beneficial for ‘bubble babies’

By Helen Albert, Senior medwireNews Reporter

Results from a long-term study published in Blood show that adding a low dose of chemotherapy prior to gene therapy can help improve outcomes in children with adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID).

The team, lead by Donald Kohn (University of California, Los Angeles, USA), found that combining chemotherapy with refined gene therapy was superior to gene therapy alone during an 11-year study, with three of the six children treated with this method continuing to have almost normal immune function 3 to 5 years post treatment.

"We were very happy that in the human trials we were able to see a benefit in the patients after we modified the protocol," commented Kohn in a press statement.

"Doctors treating ADA-deficient SCID have had too few options for too long, and we hope this will provide them with an efficient and effective treatment for this devastating disease."

The gene therapy used to treat the children involved transducing patients' bone marrow CD34+ cells using a combination of two slightly different retroviral vectors (MND-ADA and GCsapM-ADA) before reinjection.

Ten patients were treated in total, four were not given pretransplant cytoreduction chemotherapy and were treated with ADA enzyme replacement therapy (ERT) throughout the procedure. These patients showed reasonably good results, but still required ERT after treatment

The other six were given gene therapy after withdrawal from ADA-ERT and pretreatment with busulfan 65-90 mg/m². Of these, three have good immune function and do not require ERT, with peripheral blood mononuclear cell gene marking between 1-10% and near normal/normal levels of ADA gene expression. Two of the other patients had to restart ERT and one subsequently needed a hematopoietic stem cell transplant.

"This is a highly rewarding study for those of us in the clinic and lab," said co-author Fabio Candotti (National Institutes of Health, Bethesda, Maryland, USA). "Not only have we realized an important advancement in gene therapy, but we have seen a renewal of health in our patients."

The authors explain that further refinement of the treatment - involving use of a slightly different viral vector - will be tested in the next phase of the study, which is currently recruiting patients.

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