DISCOVER HKBU

Encouraging breakthrough in rare bone disease treatment

28 Jan 2025

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Professor Zhang Ge, Associate Dean (Research) of Chinese Medicine and Director of the Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases at HKBU, in collaboration with other institutions, has developed an aptamer for the treatment of X-linked hypophosphatemia, which has been granted Orphan Drug Designation and Pediatric Rare Disease Designation by the U.S. FDA.
Professor Zhang Ge, Associate Dean (Research) of Chinese Medicine and Director of the Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases at HKBU (2nd left), and his research team.

A groundbreaking discovery from researchers at HKBU and the Shanghai Sixth People’s Hospital offers new hope for treating X-linked hypophosphatemia (XLH), a rare bone disease. This innovative approach utilises an aptamer originally designed for osteogenesis imperfecta, which has recently received special recognition from the U.S. Food and Drug Administration (FDA) as both an Orphan Drug and a Pediatric Rare Disease treatment.

 

Understanding X-Linked Hypophosphatemia (XLH)

XLH, (“X” denotes X-chromosome, a sex-determining chromosome), is a rare bone disease characterised by hypophosphatemia (low phosphate levels in the blood). It results from a mutation in a gene responsible for regulating phosphate levels.  When phosphate levels drop too low, it hinders proper bone mineralisation, leading to softer bones that can cause deformities and growth issues. Adults with XLH might experience pain, changes in body shape, shorter stature and pseudo-fractures, leading to reduced mobility or even disability.

Professor Zhang Ge, Associate Dean (Research) of Chinese Medicine and Director of the Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases at HKBU, and Professor Zhang Zhenlin, Director of Osteoporosis and Bone Diseases of the Shanghai Sixth People’s Hospital, along with Aptacure Therapeutics Ltd., have developed a long-acting sclerostin-loop3 oligonucleotide aptamer for the treatment of XLH. This aptamer was granted Orphan Drug Designation and Pediatric Rare Disease Designation earlier by the U.S. FDA for treatment of XLH.

 

The role of Sclerostin and Apc001

Central to this research is sclerostin, a protein that plays a vital role in bone growth while also protects heart health. Excessive sclerostin can inhibit bone formation. Interestingly, studies indicate that when sclerostin loses a specific segment known as the “loop3 domain,” bone strength improves without compromising cardiovascular health. This finding paves the way for new treatment options.

The research team further identified oligonucleotide aptamers, particularly Apc001, which can inhibit the sclerostin loop3. Animal studies demonstrated that Apc001 promotes bone formation without increasing cardiovascular risk, while significantly elevating blood phosphorus levels in mice with XLH. This positions Apc001 as a promising candidate for targeted XLH treatment.

 

Hope for XLH patients

With both Orphan Drug and Pediatric Rare Disease designations from the FDA, Apc001 is on a fast track for clinical trials, promising potential relief for patients. These designations provide advantages such as fewer required clinical trial samples and a seven-year market exclusivity period.

Currently, pilot-scale production of Apc001 has been completed, and it is undergoing preclinical toxicological assessment by a third party. Apc001 is scheduled to enter clinical trials in both Mainland China and the U.S.