In early December 2020, mRNA medicines company Arcturus Therapeutics Holdings Inc. (“Arcturus”) announced that the company begun dosing participants within its Phase 1b clinical trial. Within the trial, researchers will evaluate ARCT-810 for the treatment of patients with ornithine transcarbamylase (OTC) deficiency. Currently, there are few treatments for this condition.
Overall, Arcturus developed ARCT-810 using the company’s own proprietary mRNA therapy platform. The treatment is administered via the LUNAR lipid-mediated delivery. Through this, ARCT-810 delivers OTC messenger RNA (mRNA) directly to affected liver cells. Not only is this treatment targeted, but it offers the chance to reduce neurological and liver damage. Preclinical studies highlight ARCT-810 and its beneficial impact on survival rate.
12 patients enrolled in the Phase 1b trial. During the trial, patients will receive either 0.2 mg/kg or 0.4 mg/kg ARCT-810. In the Phase 1 trial, researchers found the treatment to be safe and well-tolerated, with a positive pharmacokinetic profile. In this study, researchers will advance their knowledge on the safety, efficacy, pharmacokinetic profile, and tolerability of ARCT-810.
Ornithine Transcarbamylase (OTC) Deficiency
Caused by an OTC gene mutation, ornithine transcarbamylase (OTC) deficiency is a genetic urea cycle disorder. Normally, the OTC gene prompts the production of the OTC enzyme. However, when the gene is mutated, the enzyme does not work properly. This negatively impacts the urea cycle, causing ammonia to build-up in the blood. High levels of ammonia are toxic and inhibit liver and nervous system function. Because OTC deficiency is an X-linked condition, males are impacted more significantly than females.
There are multiple forms of OTC deficiency, including neo-natal onset and late-onset. In the first, more severe form, symptoms include:
- Failure to thrive
- Fatigue and lethargy
- Refusal to eat and poor sucking
- Liver enlargement
- Low muscle tone
- Cerebral palsy
- Respiratory distress
- Developmental and intellectual delays
In the late-onset form, which usually occurs following another condition, symptoms include:
- Impaired coordination
Without treatment, both forms of OTC deficiency can be fatal. Learn more about OTC deficiency.