OP005: AT-007 significantly reduces toxic galactitol in ACTION-galactosemia kids - the 1st therapeutic interventional clinical trial in children with classic galactosemia

Sorbitol reduction via govorestat ameliorates synaptic dysfunction and neurodegeneration in sorbitol dehydrogenase deficiency

“…Proper mitochondrial function is critical for maintaining the neuronal function, as neurons have high-energy demands to maintain their membrane potential and survival of distal axons ( 12 ). Mitochondrial abnormalities have been implicated in many hereditary neuropathies ( 10 , 11 ). Compromised mitochondrial function can contribute to peripheral neuropathies by impairing mitochondrial integrity, membrane potential loss, ATP depletion, and subsequent neuronal death ( 12 , 15 , 16 ).…”

“…AT-007 from Applied Therapeutics has received Orphan Drug and Pediatric Rare Disease designations from the FDA to treat SORD deficiency, Galactosemia, and phosphomannomutase-2 deficiency, a congenital disorder of glycosylation (PMM2-CDG) featured by increased sorbitol level ( 32 ). Preliminary data from the ongoing first therapeutic interventional clinical trial in children aged 2–17 with Classic Galactosemia show that AT-007 significantly reduced toxic galactitol in patients with pediatric Galactosemia and demonstrated a safe and well-tolerated profile ( 10 ). A placebo-controlled phase III clinical trial is ongoing to evaluate the efficacy of AT-007 on sorbitol reduction and clinical outcomes of patients with SORD deficiency (NCT05397665).…”

“…AT-007 is a central nervous system (CNS) penetrant, orally active ARI with IC 50 of 100 pM. AT-007 has been shown to reduce toxic galactitol levels and prevent disease complications in galactose-1-phosphate uridyl transferase deficiency (10), and its effect on SORD deficiency is being evaluated in a Phase 3 trial.…”