STARS-mito
Research type
Research Study
Full title
Supplementation with Targeted Amino acids in mitochondrial Aminoacyl-tRNA Synthetase diseases (STARS-mito)
IRAS ID
352254
Contact name
Rita Horvath
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and University of Cambridge (joint sponsors)
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Transfer RNAs (tRNAs) are small molecules that play a key role in making the growing chain of amino acids that form a protein. The process of attaching amino acids to their matching tRNA is called aminoacylation. Mitochondrial aminoacyl-tRNA synthetases (mt-ARS) are the enzymes needed for aminoacylation of tRNAs with their corresponding amino acid during protein production in the mitochondria. There are 17 mt-ARS and variants in them are an important cause of mitochondrial disease in children. Each mt-ARS is responsible to add a particular amino acid to the corresponding tRNA and therefore defects in these enzymes are thought to impair mitochondrial protein synthesis. Most of these disorders affect the central nervous system but some affect multiple other organs. There are no effective cures, and treatment manages symptoms only. The rarity, diverse presentation, limited preclinical models, lack of biomarkers, and unpredictable progression are challenges in therapy development. The amount of the corresponding amino acids may impact aminoacylation efficiency, especially in the presence of disease-causing variants. We hypothesise that supplementation with the amino acid relevant for a particular mt-ARS increases the amino acid availability and improves mitochondrial protein production, and therefore function, in mt-ARS disorders.
This experimental medicine study will evaluate the effect of supplementation with corresponding amino acid on mitochondrial function in 10 patients with one of three more common forms of mt-ARS diseases: AARS2 (mitochondrial alanyl-tRNA synthetase), EARS2 (mitochondrial glutamyl-tRNA synthetase), and DARS2 (mitochondrial aspartyl-tRNA synthetase). We will assess how amino acid and mitochondrial metabolism changes in response to supplementation using a number of biochemical tests. Physiological, motor and cognitive parameters and participant reported outcomes will be assessed. Participants will attend 8 visits (including 2 virtual) across a period of up to 42 weeks. Participants will receive the amino acid corresponding to their disease at increasing dose levels for 24 weeks.
REC name
West of Scotland REC 1
REC reference
25/WS/0088
Date of REC Opinion
20 Oct 2025
REC opinion
Further Information Favourable Opinion