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    We are now developing a novel investigative therapeutic agent (ARU-2801) for the potential treatment of hypophosphatasia (HPP). Hypophosphatasia is an inherited bone disease caused by mutations in the gene for tissue-nonspecific alkaline phosphatase (TNALP) 1). The disease is classified into six types based on age of onset and clinical symptoms, with the severe perinatal and infantile types having a poor prognosis. We have been studying gene therapy for hypophosphatasia for many years, and succeeded to treat HPP infantile model mice deficient in the Alpl gene (Alpl-/- mice) 2) by intravenous administration of lentiviral vectors expressing TNALP 3) or adeno-associated virus (AAV) vectors 4) , intrauterine fetal therapy with an AAV vector 5), transplantation of hematopoietic stem cells transduce with lentiviral vectors 6), and intramuscular administration of AAV vectors 7-10). The treatment of HPP Alpl-/- mice has shown therapeutic effects such as prolonged survival and improved bone formation (Table 1).

Table1 Gene therapy research for hypophosphatasia


TU: Transduction Unit, vg: vector genome, IV: Intravenous, IU: Intrauterine, BMT: Bone marrow transplantation, IM: Intramuscular

    Among these therapies, we are developing an investigational therapy using intramuscular administration of TNALP-expressing AAV type8 vectors, which we believe may provide benefits as a one-time treatment.


    ARU-2801 is a type 8 adeno-associated virus vector that expresses TNALP and is currently under development as a regenerative medicine product (gene therapy drug). The intended TTP (Target Product Profile) of ARU-2801 is shown in Table 2.

Table 2 Intended TPP of Investigational Produt ARU-2801 for Hypophoshatasia

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    ARU-2801, an invesgitave one-time treatment, has the potential increase survival for the most severe forms of untreated hypophosphatasia and potentially improve ADL and quality of life for all patients with hypophosphatasia.


1)    Henthorn PS, Whyte MP: Clin Chem, 38: 2501 (1992)

2)    Narisawa S et al: Dev Dyn, 208: 432 (1997)

3)    Yamamoto S et al: J Bone Miner Res, 26: 135 (2011)

4)    Matsumoto T et al: Hum Gene Ther, 22: 1355 (2011)

5)    Sugano H et al: Hum Gene Ther, 23: 399 (2012)

6)    Iijima O, et al: Hum Gene Ther, 26: 801 (2015)

7)    Nakamura-Takahashi A, et al: Mol Ther Methods Clin Dev, 3: 15059 (2016)

8)    Miyake K et al: Selected Topics in Neonatal Care. (Edited by R. Mauricio Barria, Published by InTech) 191 (2018)

9)    Matsumoto T et al: Mol Ther Methods Clin Dev, 22: 330 (2021)

10)    Kinoshita Y et al: J Bone Miner Res, 36: 1835 (2021)

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