Disease Characteristics: OTC deficiency is a rare, X-linked genetic disorder that is characterised by complete or partial lack of the OTC enzyme. OTC is a key component of the urea cycle and patients with OTC deficiency accumulate nitrogen waste in the form of excess ammonia (hyperammonaemia) in the blood, causing hyperammonaemic decompensations with symptoms including vomiting, impaired voluntary movement and progressive lethargy. If left untreated, these may progress to coma and life-threatening complications. While later onset disease can occur in adults with a milder form of the disorder, symptoms present within a few days of birth of males with severe OTC. Patients are rapidly diagnosed (urine and blood biochemical analyses, gene sequencing) when they present at hospital/are admitted to intensive care with acute hepatic decompensation and hyperammonaemia.
Unmet Need: Current standard of care involves protein-restricted diets and ammonia-scavenger medications; however, these approaches can have a significant impact on patients’ quality of life and patients still face a lifelong risk of decompensation and neurological damage resulting in intellectual disability, developmental delays, and movement disorder. Liver transplant is the only curative option, but is often unavailable and comes with significant morbidity/mortality risk and lifelong immunosuppression and arginine supplementation.
Epidemiology: Over 10,000 patients suffering from OTC deficiency have been identified worldwide.
BGT-OTCD was initially developed by Prof Alexander and Associate Prof Lisowski of Children’s Medical Research Institute (CMRI) at Westmead, Australia, in collaboration with Prof Gissen from UCL.
BGT-OTCD has completed preclinical efficacy, safety and biodistribution studies and will be evaluated in HORACE (Halting Ornithine transcarbamylase deficiency with Recombinant AAV in ChildrEn), a phase 1/2 clinical trial which will be initiated mid-2023. BGT-OTCD has been granted orphan drug designation by the European Medicines Agency (EMA).
J Baruteau et al. Mol Ther Methods & Clin Dev. 2021 Sep 14; 23:135 -146
