Aspartoacylase (ASPA) (ASPA)

Aspartoacylase (ASPA) is a critical metabolic enzyme predominantly expressed in the oligodendrocytes of the central nervous system (CNS) [1, 2]. Its primary biological function is the hydrolysis of N-acetyl-L-aspartate (NAA) into acetate and L-aspartate, a process essential for providing the acetate required for myelin lipid synthesis [2, 3]. Deficiency of this enzyme, caused by mutations in the ASPA gene, leads to Canavan disease, a fatal autosomal recessive leukodystrophy characterized by spongy degeneration of the brain and severe developmental delays [3, 4]. The pathology is driven by both the toxic accumulation of NAA and the lack of acetate for proper myelination [4]. Current therapeutic approaches are centered on gene therapy, utilizing adeno-associated viral (AAV) vectors to deliver a functional copy of the ASPA gene directly to CNS cells [5, 6]. These investigational treatments aim to restore enzymatic activity, reduce NAA levels, and promote the stabilization or recovery of white matter [6]. Clinical trials are currently evaluating the safety and efficacy of these gene replacement strategies in pediatric patients [5]. Sources: [1] UniProt (P45381); [2] Madhavarao et al. (2005) PMID: 15866503; [3] NIH/GARD Canavan Disease; [4] Matalon et al. (1988) PMID: 3335204; [5] BridgeBio/Aspa Therapeutics (BBP-812); [6] Myrtelle Inc. (rAAV-Olig001-ASPA).

Other names

N-acetylaspartate amidohydrolaseACY2Aminoacylase-2N-acetylaspartase

Gene replacement therapy to restore functional aspartoacylase enzyme activity in the central nervous system.