OTL-103

OTL-103 is an investigational gene therapy being developed by Orchard Therapeutics. It utilizes autologous hematopoietic stem cells (HSCs) transduced with a lentiviral vector to deliver a functional copy of the ADA gene to patients with adenosine deaminase severe combined immunodeficiency (ADA-SCID).

ADA-SCID is a rare, life-threatening inherited disorder caused by mutations in the ADA gene, which leads to a deficiency of the adenosine deaminase enzyme. This enzyme is crucial for the metabolism of adenosine and deoxyadenosine. Without functional ADA, toxic metabolites accumulate, particularly in lymphocytes, leading to severe immune dysfunction and rendering affected individuals highly susceptible to infections.

OTL-103 aims to correct the underlying genetic defect by introducing a working copy of the ADA gene into the patient's own HSCs. These modified HSCs are then transplanted back into the patient, with the goal of engrafting and differentiating into various blood cell types, including lymphocytes, which now express the functional ADA enzyme. This could potentially restore immune function and eliminate or reduce the need for enzyme replacement therapy (ERT) or hematopoietic stem cell transplantation from a matched donor.

Clinical trials are ongoing to evaluate the safety and efficacy of OTL-103 in patients with ADA-SCID. The therapeutic approach targets a genetic cause of the disease, providing a potentially long-term solution.