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Gene therapy approaches for osteogenesis imperfecta

Gene Therapy volume 11, pages 408–416 (2004)Cite this article

Abstract

Osteogenesis imperfecta (OI) is a heterogeneous group of genetic disorders that affect connective tissue integrity. The hallmark of OI is bone fragility, although other manifestations, which include osteoporosis, dentigenesis imperfecta, blue sclera, easy bruising, joint laxity and scoliosis, are also common among OI patients. The severity of OI ranges from prenatal death to mild osteopenia without limb deformity. Most forms of OI result from mutations in the genes that encode either the proα1or proα2 polypeptide chains that comprise type I collagen molecules, the major structural protein of bone. Treatment depends mainly on the severity of the disease with the primary goal to minimize fractures and maximize function. Current treatments include surgical intervention with intramedullarly stabilization and the use of prostheses. Pharmacological agents have also been attempted with limited success with the exception of recent use of bisphosphonates, which have been to shown to have some effect. Since OI is a genetic disease, these agents are not expected to alter the course of the collagen mutations. Cell and gene therapies as potential treatments for OI are therefore currently being actively investigated. The design of gene therapies for OI is however complicated by the genetic heterogeneity of the disease and by the factor that most of the OI mutations are dominant negative where the mutant allele product interferes with the function of the normal allele. The present review will discuss the molecular changes seen in OI, the current treatment options and the gene therapy approaches being investigated as potential future treatments for OI.

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Acknowledgements

The work presented in this review was supported in part by a grant from Children's Brittle Bone Foundation and NIH Grants AR4712 and R01 AR049688.

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Author notes

  1. C Niyibizi

    Present address: Orthopaedics and Rehabilitation, HO89, Penn State College of Medicine, 500 University Drive, Hershey, PA, 17033

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Ferguson Laboratories for Orthopaedic Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    C Niyibizi & S Wang

  2. Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    C Niyibizi

  3. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Z Mi & PD Robbins

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Correspondence to C Niyibizi.

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Niyibizi, C., Wang, S., Mi, Z. et al. Gene therapy approaches for osteogenesis imperfecta. Gene Ther 11, 408–416 (2004). https://doi.org/10.1038/sj.gt.3302199

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