Effect of L1-79 on Core Symptoms of Autism Spectrum Disorder: A Case Series

AbstractPurposeThis study examines the effects of the tyrosine hydroxylase inhibitor L1-79, a racemic formulation of α-methylparatyrosine, in patients with autism spectrum disorder (ASD) in a prospective case series. The l-isomer formulation of α-methylparatyrosine, metyrosine, is approved for the management of patients with pheochromocytoma. MethodsSix male and 2 female patients aged 2.75 to 24 years with ASD were treated for 8 weeks at L1-79 doses ranging from 90 to 400 mg thrice daily. Assessments at weekly intervals included the Aberrant Behavior Checklist–Community (ABC-C), Connor's Parent Rating Scale (CPRS), and Clinical Global Impressions (CGI) scale. The Autism Diagnostic Observation Schedule (ADOS) was administered at baseline and week 10. FindingsThe ABC-C and CPRS scores improved between baseline and end of study for 7 of 8 participants; most participants' assessment scores decreased. At week 8, the CGI efficacy index was 05 for 6 of 8 participants, indicating modest improvement with at least partial resolution of symptoms and no medication adverse effects, and 09 for 2 participants, indicating minimal improvement and no change in status or care needs, without adverse effects. The mean ADOS scores improved by ≥31% for 4 of the 6 participants tested, with 1 patient experiencing a 47% improvement. Seven of the 8 participants previously taking psychotropic medications were stable without their legacy medications while receiving L1-79, and 1 patient resumed a single legacy medication at a lower dose. Three adverse events were reported; symptoms were mild and resolved without change in therapy. ImplicationsThese results suggest L1-79 may be a tolerable and effective treatment for the core symptoms of ASD, which must be confirmed with double-blind studies.