Hypophosphatasia is a genetic disorder that disrupts the healthy mineralization of bones and teeth. Symptoms include weakened bones and teeth, reduced mobility, skeletal malformation and joint pain. The disorder affects infants, children and adults and has a significant cost to quality of life and the healthcare system. The biological cause is a mutation of the ALPL gene, which is involved in making the alkaline phosphatase enzyme, required for the mineralization process.
Treatment is primarily symptomatic care. Developments in FDA-approved enzyme replacement therapy (‘asfotase alfa’) have provided novel treatment avenues; significant improvements in bone tissue and been reported with limited side effects. However, this treatment remains restricted to paediatric-onset hypophosphatasia. Other treatments are in development.
PuREC solution – in-vivo REC-MSC engraftment
PuREC specializes in regenerative cell therapy using mesenchymal stem cells (MSCs). MSCs are multipotent cells that differentiate into various mesenchymal lineage cells, including bone. MSCs have low immunogenicity and are a promising candidate for human cell therapy. Advancements in human bone marrow cells isolation have led to the extraction of an extremely pure and rapidly expanding MSC population (Mabuchi et al., 2013). This clonal isolation is achieved by selecting cell surface markers related to enriched clonogenic cells. These cells (REC) exhibit improved self-renewal and multilineage differentiation, highly relevant to cell therapy. In parallel, an initial clinical study infusing MSCs in patients with severe HPP has shown improvement in bone mineralization and bone function (Taketani et al., 2015).
PuREC aims to capitalize on these technologies to enable the engraftment of MSCs (REC-MSC) for the treatment of hypophosphatasia. The benefits of this cell therapy may extend beyond infantile hypophosphatasia and be of great clinical importance. PuREC is en-route to deliver efficient, purer and safer cell therapy.
Mabuchi, Y., Morikawa, S., Harada, S., Niibe, K., Suzuki, S., Renault-Mihara, F., Houlihan, D.D., Akazawa, C., Okano, H. and Matsuzaki, Y., 2013. LNGFR+ THY-1+ VCAM-1hi+ cells reveal functionally distinct subpopulations in mesenchymal stem cells. Stem cell reports, 1(2), pp.152-165.
Taketani, T., Oyama, C., Mihara, A., Tanabe, Y., Abe, M., Hirade, T., Yamamoto, S., Bo, R., Kanai, R., Tadenuma, T. and Michibata, Y., 2015. Ex vivo expanded allogeneic mesenchymal stem cells with bone marrow transplantation improved osteogenesis in infants with severe hypophosphatasia. Cell transplantation, 24(10), pp.1931-1943.