Hypophosphatasia (HPP) is a rare, genetic, metabolic disease that affects the development of bones and teeth. The disease was initially recognized in 1948. Now it is well established that HPP results from mutations in the alkaline phosphatase (ALP) gene ALPL, which encodes tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). TNSALP is a phosphomonoesterase. Mutations in ALPL leads to low alkaline phosphatase activity levels and ultimately to rickets and osteomalacia. Individuals with HPP may experience metatarsal and femoral stress fractures or pseudofractures, pathological fractures after minimal trauma, muscle and joint pain, and osteomalacia. Currently, the diagnosis of HPP is mainly based on low serum ALP enzyme activity, high endogenous levels of TNSALP substrates, and ultimately mutations in the ALPL gene.
It is believed that bone anabolic and/or enzyme replacement treatment strategies could treat HPP. One such therapy called asfotase alfa (Strensiq, Alexion) has already been approved for long-term treatment of pediatric-onset HPP in several countries. Previous clinical trials have shown that asfotase alfa improve survival of patients with severe perinatal/infantile onset of HPP. But due to regulatory specifications, access to asfotase alfa is limited.
Now a team of researchers from the University of Wurzburg, Novartis Pharma AG, and Novartis Institutes for BioMedical Research Inc. has tested the effectiveness of anti-sclerostin monoclonal antibody BPS804 in adult patients with HPP. The found that BPS804 treatment was well tolerated and resulted in increases in bone formation biomarkers and bone mineral density.
The study, titled “Efficacy of anti-sclerostin monoclonal antibody BPS804 in adult patients with hypophosphatasia,” appears in The Journal of Clinical Investigation. Lothar Seefried is the first author.
BPS804 is a high-affinity, fully human, neutralizing, anti-sclerostin monoclonal antibody. Previous studies have shown that this antibody is active in vitro, and is effective against osteoporosis in animal models. In the study, adult patients with HPP were treated with BPS804. The researchers investigated the pharmacodynamics, pharmacokinetics, preliminary efficacy, and safety of BPS804. Results showed that this antibody may improve bone mineral density, stability, and regeneration in non-life-threatening clinical situations in adults with HPP. (Cusabio offers polyclonal antibody.)
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