Ornithine transcarbamylase (OTC) deficiency is a disorder that can cause comas, seizures, and death, making it necessary for those affected to seek treatment. Arcturus Therapeutics aims to give those with OTC deficiency a treatment option with ARCT-810, their mRNA therapeutic. It has recently been approved for clinical trials by the FDA and New Zealand Medicines and Medical Devices Safety Authority (Medsafe). If these trials are successful, OTC deficiency patients will have a new treatment option.
About OTC Deficiency
OTC deficiency is a urea cycle disorder that leads to an accumulation of ammonia in the blood, which becomes toxic and affects the nervous system and liver. There are multiple forms of this disorder, defined by the severity of symptoms and age of onset. One of every 14,000 to 77,000 people are affected by OTC deficiency. It is a result of a mutation in the OTC gene, which is responsible for the ornithine transcarbamylase enzyme. This mutation is inherited in an X-linked pattern, meaning males are more likely to be affected than females.
Symptoms for the more severe form, which sees the onset soon after birth, include lethargy, a loss of appetite, a poorly controlled breathing rate and body temperature, seizures, comas, intellectual or developmental disabilities, and damage to the liver. The form with a later onset sees effects like episodes of altered mental status, headaches, loss of appetite, vomiting, and seizures.
Blood and urine tests will be performed to obtain a diagnosis. It can be confirmed through genetic testing. Treatment is meant to stop the ammonia from building up, using methods like dietary restrictions and alternative pathways therapy.
About ARCT-810
ARCT-810 is an mRNA therapeutic that is systemically administered in a low dose. It delivers OTC mRNA to the cells in the liver using Arcturus’ LUNAR delivery system. This has the potential to fix the urea cycle activity and stop the buildup of ammonia, which would then effectively stop the characteristic symptoms. Its preclinical data has allowed it to be granted the Orphan Drug designation by the FDA.
The Clinical Trials
There will be two studies of this drug, as the FDA and Medsafe both approved trials. Both primary endpoints will include safety and tolerability, while exploratory endpoints will include various biomarkers.
Researchers plan to recruit 30 healthy participants for the New Zealand trial and 12 OTC deficiency patients for the American study. Those in the New Zealand portion should be enrolled soon, but the American leg of the study is waiting to see the developments of the current COVID-19 pandemic.
Researchers are hopeful that these trials will be successful. That would mean success for Arcturus Therapeutics, as it is becoming a clinical stage company. It also means that OTC deficiency patients may have a disease modifying therapy.
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