Intra-Articular Lubricin Gene Therapy for Post-Traumatic Arthritis

Abstract

Twenty-six rabbits underwent sham or ACLT surgery and were euthanized at 4 or 8 weeks post-op, completing live animal work for Major Task 1. Histologic processing was completed and safranin-O-stained sections were scanned. All rabbits that underwent surgery survived to the scheduled endpoints without apparent complications. However, the 10 rabbits euthanized at 4 weeks (5 sham and 5 ACLT) all had joint effusions, indicating an inflammatory reaction to AAV. Effusions were not evident in our initial one-week pilot study designed to detect such responses. A review of AAV titers indicated that the preparation used in the 4-week study was ~ 2-fold more concentrated than that used in the earlier study, suggesting that the effusions were provoked by viral overload. Given these events it would appear prudent to better define the maximum tolerated dose of AAV before beginning Major Task 2, which calls for treatment after OA progression is already underway.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2016
Accession Number
AD1032858

Entities

People

  • James A. Martin

Organizations

  • University of Iowa

Tags

DTIC Thesaurus Topics

  • Arthritis
  • Biomedical Research
  • Cartilage
  • Confocal Microscopy
  • Data Analysis
  • Effusion
  • Electronic Mail
  • Gene Delivery
  • Gene Therapy
  • Histology
  • Medical Personnel
  • Peptide Growth Factors
  • Pilot Studies
  • Surgery
  • Technicians
  • Therapy
  • Tissues

Fields of Study

  • Medicine

Readers

  • Molecular Genetics
  • Neurotrauma and Rehabilitation Medicine.

Technology Areas

  • Biotechnology