TNAP-D10

TNAP-D10 is a mineral-targeted form of tissue-nonspecific alkaline phosphatase (TNAP) designed to treat hypophosphatasia (HPP) and other heritable osteomalacia disorders. It consists of the TNAP enzyme carrying a deca-aspartate (D10) motif that directs the protein specifically to bone and teeth, where it hydrolyzes extracellular inorganic pyrophosphate (PPi), a potent inhibitor of mineralization. TNAP-D10 is being developed both as a recombinant enzyme replacement therapy and as a gene therapy delivered via an adeno-associated virus serotype 8 (AAV8) vector (AAV8-TNAP-D10, also known as ARU-2801). Originally developed by Sanford Burnham Prebys and Nippon Medical School, the gene therapy program was licensed to Aruvant Sciences (a Roivant subsidiary) but was subsequently discontinued in 2022 during a pipeline reprioritization. Preclinical research continues in academic settings, demonstrating efficacy in improving skeletal and dental phenotypes in mouse models of infantile and late-onset HPP, as well as X-linked hypophosphatemia (XLH).

Other names

TNALP-D10TNALP-D-10TNALP-D 10mineral-targeted tissue-nonspecific alkaline phosphataserecombinant mineral-targeting tissue-nonspecific alkaline phosphatasetissue-nonspecific alkaline phosphatase-D10