A Pilot Study of a Potential Phosphopantothenate Replacement Therapy in 2 Patients with Pantothenate Kinase-Associated Neurodegeneration - Abstract
Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder linked to mutations in the PANK2 gene, presenting with mixed-motor symptoms of dystonia and parkinsonism in childhood to early adulthood. The pantothenate kinase 2 (PanK2) enzyme phosphorylates pantothenic acid to form phosphopantothenic acid (PPA), a key step in the biosynthesis of coenzyme A (CoA). We describe the treatment of 2 adult male siblings with PKAN under compassionate use authorization with fosmetpantotenate (RE-024), a molecule designed to pass the blood-brain barrier and be metabolized to form PPA in neural and glial cells. The therapy aims to restore PPA, the product of the dysfunctional PanK2 enzyme, to physiologic levels. Open, uncontrolled fosmetpantotenate treatment was associated with clinically meaningful improvement, including improved gait and overall functioning in the first 6 months, followed by stabilization of disease progression through 47 weeks. A controlled trials should be conducted to evaluate the safety and efficacy of fosmetpantotenate in patients with PKAN.