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

Abstract

PURPOSE:

This 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.

METHODS:

Six 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.

FINDINGS:

The 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.

IMPLICATIONS:

These 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.

• Authors: John Rothman, Eric J Bartky, Francis Peter Halas
• Journal: Clinical therapeutics (Clin Ther) Vol. 41 Issue 10 Pg. 1972-1981 (10 2019) ISSN: 1879-114X [Electronic] United States
• PMID: 31492568 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Methyltyrosines
• Tyrosine 3-Monooxygenase

Topics

• Adolescent
• Adult
• Autism Spectrum Disorder (drug therapy)
• Behavior (drug effects)
• Child
• Child, Preschool
• Female
• Humans
• Male
• Methyltyrosines (adverse effects, therapeutic use)
• Treatment Outcome
• Tyrosine 3-Monooxygenase (antagonists & inhibitors)
• Young Adult