OTC deficiency is a life-threatening genetic disease that affects over 10,000 people worldwide. i. Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. A lack of the OTC enzyme in liver cells can lead to life threatening accumulation of ammonia in the blood which can cause seizures, coma, and death in untreated patients. There is currently no cure for OTC deficiency. ii. Arcturus is working to develop an mRNA medicine that enables OTC patients to make healthy functional OTC enzymes in their liver cells
i. Present standard of care involves a strict diet (low protein, high fluid intake) plus ammonia scavengers (sodium phenylbutyrate) ii. The present standard of care also does not effectively prevent life-threatening spikes of ammonia iii. Severe OTC Deficiency patients are typically referred for liver transplant, currently the only cure
i. Preclinical studies have shown that our proprietary LUNAR® delivery platform safely and effectively delivers OTC mRNA to liver cells in a mouse model of OTC deficiency, resulting in restoration of disease markers to normal levels. ii. By enabling the expression of OTC enzymes in the liver, ARCT-810 creates the potential to restore normal urea cycle activity to detoxify ammonia, preventing neurological damage and removing the need for liver transplantation. iii. Were able to safely dose up to 0.4 mg/kg with no steroid pre-treatment in our Phase 1 single dose trial with health volunteers, leaving us optimistic about increasing the dose.
i. Current ammonia scavenging based treatments are extremely expensive for the patient, around $500,000/year. ARCT-810 multi-dose treatment plans to enable the replacement of patient OTC enzymes to restore the patient's normal urea cycle activity to detoxify ammonia.
i. The potential for ARCT-810 to disrupt the current standard of care for those suffering from OTC Deficiency is large. Our therapeutic aims to eliminate the need for patients to navigate symptoms by treating the disease directly and replacing the missing protein. If successful, ARCT-810 will greatly increase the livelihoods of the over 10,000 OTC patients worldwide as well as opening up the possibility of multiple new applications for our technology in the Liver.