Phase 2a/b randomised placebo-controlled dose-escalation trial of triheptanoin for ataxia-telangiectasia: treating mitochondrial dysfunction with anaplerosis.

ABSTRACT:

Background

Ataxia-telangiectasia (A-T) is a rare multisystem disease characterised by neurodegenerative cerebellar ataxia, lung disease, immune deficiency, high cancer risk, and mitochondrial dysfunction. A-T cells demonstrate defective endoplasmic reticulum-mitochondrial connectivity disrupting calcium homoeostasis and mitochondrial fusion, which are corrected in vitro by the triheptanoin metabolite, heptanoate.

Methods

We performed a Phase 2a/b trial of triheptanoin with a three-arm placebo-controlled dose-escalation design. Doses escalated at 2-month intervals for 12 months in the sequence 0%, 10%, 20%, 35% of calculated caloric intake. The primary outcome was cell death in respiratory epithelial cells. Key secondary outcomes included scales for assessment and rating of a

SUBMITTER: Lynch M 

PROVIDER: S-EPMC12271818 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature