Osteogenesis Imperfecta: Current and Prospective Therapies

Abstract

Osteogenesis Imperfecta (OI) is a group of connective tissue disorders with a broad range of phenotypes characterized primarily by bone fragility. The prevalence of OI ranges from about 1:15,000 to 1:20,000 births. Five types of the disease are commonly distinguished, ranging from a mild (type I) to a lethal one (type II). Types III and IV are severe forms allowing survival after the neonatal period, while type V is characterized by a mild to moderate phenotype with calcification of interosseous membranes. In most cases, there is a reduction in the production of normal type I collagen (col I) or the synthesis of abnormal collagen as a result of mutations in col I genes. Moreover, mutations in genes involved in col I synthesis and processing as well as in osteoblast differentiation have been reported. The currently available treatments try to prevent fractures, control symptoms and increase bone mass. Commonly used medications in OI treatment are bisphosphonates, Denosumab, synthetic parathyroid hormone and growth hormone for children therapy. The main disadvantages of these therapies are their relatively weak effectiveness, lack of effects in some patients or cytotoxic side effects. Experimental approaches, particularly those based on stem cell transplantation and genetic engineering, seem to be promising to improve the therapeutic effects of OI.

Epigenetic Alterations in Sports-Related Injuries

“…Osteogenesis imperfecta (OI) is a group of connective tissue disorders with a broad range of phenotypes, primarily characterised by bone fragility. In most cases, there is a reduction in the production of normal type I collagen (COL1) or the synthesis of abnormal collagen as a result of mutations in COL1 genes [ 191 ]. Friedman et al compared DNA samples from cases with high-grade SF and healthy controls and three missense mutations in the NEB, SLC6A18, and SIGLEC12 genes; three synonymous mutations in the ELFN2, GRK4, and LRRC55 genes displayed significantly different rates in SF cases compared with the control [ 192 ].…”

Mitral Valve Prolapse and Non-Syndromic and Syndromic Variety

“…В настоящее время существует пять клинических подтипов несовершенного остеогенеза, различающихся по степени тяжести, по течению, наиболее легким из которых является I подтип, обусловленный мутациями в генах коллагена I и II типа (COL1A1, COL1A2) [31].…”

Curative Cell and Gene Therapy for Osteogenesis Imperfecta

“…(60) Thus, while the data from preclinical and clinical studies have been mixed and inconclusive, for many, the approach still holds promise. (61) Allogenic MSC transplantation could be applied to treat other rare bone conditions, such as infants born with severe genetic hypophosphatasia. (62) Thus, breakthroughs in OI cell therapy may influence the progress of other bone diseases and vice versa.…”