Table of Contents
EXECUTIVE SUMMARY
- Introduction
- Scope and coverage of the Brief
- Key findings about the topic
SECTION 1 INTRODUCTION
- Epidemeology
- Current treatments available
- What is required of a DMOAD?
- Clinical trial design for DMOADs
- Measuring the outcome
- Radiography
- Other methods
- Biomarkers
- Cleaved Type II collagen molecules
- New collagen synthesis
- Protoglycan aggrecan
- COMP (Cartilage oligomeric matrix protein)
- Bone
- Pain Scales
- Drug delivery
- Ethnic differences in response
SECTION 2 DMOADS IN THE PIPELINE
- Preventing cartilage degradation
- Overview table
- Matrix Metalloproteinase (MMP) Inhibition
- Doxycycline – Indiana University – Phase II
- Oral MMP inhibitor - P&G - Pre-clinical
- CMT-3 – Collagenex – Discovery
- Esculetin – National Defense College, Japan
– Pre-clinical
- Interleukin –1 (IL-1) inhibition
- Kineret – Amgen – Phase I
- Diacerein - University Rene Descartes, France –
PII
- Insulin
- Slow release Insulin – Genentech –
Pre-clinical
- Steroidal compounds
- DHEA – Seoul National University Hospital –
Pre-clinical
- Enhancing cartilage repair
- Overview table
- Growth factors
- Transforming Growth Factor (TGF)
- Insulin-like Growth Factor (IGF-1)
- Biomechanical and tissue engineering technologies
- Autologous chondrocyte transplantation (ACT)
- Polymer scaffold - Rice University/ NIH - Pre clinical
- BST-CarGel – Biosyntech – Phase I
- Chondrogen – Osiris – Pre-clinical
- Other mechanisms
- Overview table
- Photodynamic treatment
- Electromagnetic fields
- Glucosamine and Chondroitin Sulphate (GCS)
- Estrogen
- Estrogen receptors
- Conclusions
- Discontinued trials
- MMP inhibitor (BAY 12-9566) – Bayer – PII
discontinued
- Insulin Growth Factor (IGF) – Chiron – PII
discontinued
SECTION 3 COMPARISON OF DMOAD METHODS
- DMOAD deadlock
- Comparison of technologies
APPENDIX
- Contributing experts
- Bibliography
- Epidemiology
- Clinical trial design
- Clinical trial data
- Research methodology
- Disclaimer
List of Tables
- Table 1: OA current and future estimated prevalence by
country, 2003 and 2010
- Table 1: Combination and monotherapies, in the seven
major markets, %, 2003
- Table 2: Pros and cons of other end-point measurement
methods
- Table 3: DMOADs using the cartilage degradation
prevention mechanism, 2003
- Table 4: Pain responses in knee OA after a single
intra-articular injection of Kineret (anakinra)
- Table 5: Cartilage repair enhancing drugs or
technology, 2003
- Table 6: ACT trials from the Journal of Bone and Joint
Surgery, 2003
- Table 7: Other mechanisms of disease modification,
2003
- Table 8: Summary of DMOADs in development
List of Figures
- Figure 1: Combination and monotherapies, in the seven
major markets, 2003
- Figure 2: Cartilage remodeling
- Figure 3: Generation of some of the cartilage
biomarkers
- Figure 4: Constraints and drivers of DMOAD development
- Figure 5: Comparison of products addressing the
balance of cartilage degradation or repair, 2003
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