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The joint project of The Sixth People's Hospital of Shanghai Jiao Tong University School of Medicine and Hong Kong Baptist University on " Clinical precision diagnosis and treatment of hereditary bone diseases based on molecular understandings" won the Fi

2024-10-25

The joint project "Clinical precision diagnosis and treatment of hereditary bone diseases based on molecular understandings", applied by the Sixth People's Hospital of Shanghai Jiao Tong University School of Medicine and Sau Fai Institute for Advancing Translational Medicine in Bone & Joint Diseases (TMBJ), the partner organizations of Aptacure Therapeutics Limited, was awarded the First-class prize of Shanghai Science and Technology Progress Award.

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The Shanghai Science and Technology Progress Award is approved by the Science and Technology Award Committee, and approved by Shanghai Municipal People's Government after the preliminary evaluation, reassessment and final evaluation by the evaluation experts, and is committed to accelerating the construction of scientific and technological innovation, enhancing the ability of scientific and technological innovation, following up the innovation vitality of scientific researchers and creating a favorable environment conducive to scientific and technological innovation, which is highly influential and has a high status in the city and even in the whole country.

 

The project has established the largest sample size and the most diverse genetic bone disease gene bank (1,919 families with 4,939 cases) to date, with a molecular diagnosis rate of 59.1%, and mapped the clinical phenotype spectrum of the major types of hereditary bone diseases and the mutation spectrum of the causative genes in the country, which will provide a strong support for the clinical diagnosis and treatment as well as for the research.

 

Osteogenesis imperfecta (OI, also known as glass dolls or porcelain dolls) is a rare genetic bone disease and  there is a lack of effective therapeutic drugs for this disease. The joint team notably found that serum sclerostin levels were significantly higher in OI patients than in the healthy controls; sclerostin could inhibit bone formation and protect the cardiovascular system via different structural domains (loops); sclerostin loop3 contributed to the antagonistic effect of sclerostin on bone formation, while the protective effect of sclerostin on the cardiovascular system was independent of sclerostin loop3.

 

Based on the above molecular targeting findings, in collaboration with Aptacure Therapeutics Limited, a Hong Kong Science Park and SPH-Inno coincubation company, the joint research team screened and synthesized the nucleic acid aptamer Apc001 specifically targeting sclerostin loop 3 based on the above results. The sclerostin loop3-specific aptamer Apc001 was proved to promote bone formation, increase bone mass, and improve bone microarchitecture integrity in OI mice, while had no influence in the cardiovascular events progression in the mouse model of cardiovascular disease. The U.S. FDA has granted Apc001 an Orphan Drug Designation (DRU-2022-9087) and a Paediatric Rare Disease Designation (RPD-2022-667) for treating OI. This research project has started the process of industrial translation of China's first nucleic acid aptamer new drug research (entering the pilot stage). Currently, it is planned to file IND in both China and United States for the treatment of OI, and the indications will be further expanded to osteoporosis in the future.

 

So far, the joint team has published 67 representative papers, obtained 4 authorized invention patents, co-led the formulation of 3 guidelines/consensus. The relevant diagnostic and treatment strategies have been adopted by more than 200 domestic and foreign medical institutions, which has enabled Chinese clinical research, basic research and drug translation research of hereditary bone diseases to enter a new stage of rapid development, and significantly enhanced the international influence.

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