The joint project "Molecular Mechanisms and Clinical Precision Diagnosis and Treatment of Hereditary Bone Diseases", jointly 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 Prize of the Shanghai Medical Science and Technology Award.
The Shanghai Medical Science and Technology Award was established by the Shanghai Medical Association, which is committed to leading the development of medical science and technology innovation, promoting the transformation of medical science and technology achievements, and playing an essential role in improving medical science and technology innovation ability, promoting the popularization of advanced medical science and technology, and fostering the development of medicine and healthcare cause in the city, which has a higher influence and status in Shanghai and even in China.
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 http://www.aptacure.com), a Hong Kong Science Park and SPH-Inno coincubation company, the joint research team used the innovative artificial intelligence-assisted high-throughput aptamer screening and synthetic modification technologies established at the Hong Kong International Genome Research Centre of HKBU to screen and synthesize 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.