Gene therapy approaches for osteogenesis imperfecta

Christopher Niyibizi, S. Wang, P. D. Robbins

Research output: Contribution to journalReview article

30 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)408-416
Number of pages9
JournalGene Therapy
Volume11
Issue number4
DOIs
StatePublished - Feb 1 2004

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Osteogenesis Imperfecta
Genetic Therapy
Inborn Genetic Diseases
Mutation
Alleles
Therapeutics
Joint Instability
Bone and Bones
Sclera
Genetic Heterogeneity
Metabolic Bone Diseases
Diphosphonates
Scoliosis
Cell- and Tissue-Based Therapy
Collagen Type I
Connective Tissue
Osteoporosis
Prostheses and Implants
Collagen
Extremities

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Niyibizi, Christopher ; Wang, S. ; Robbins, P. D. / Gene therapy approaches for osteogenesis imperfecta. In: Gene Therapy. 2004 ; Vol. 11, No. 4. pp. 408-416.
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Gene therapy approaches for osteogenesis imperfecta. / Niyibizi, Christopher; Wang, S.; Robbins, P. D.

In: Gene Therapy, Vol. 11, No. 4, 01.02.2004, p. 408-416.

Research output: Contribution to journalReview article

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