Towards a targeted therapy for arthritis

We have developed a new drug delivery technology that allows the drug to be protected from being degraded in the body and targets it to the site of disease. The drug delivery system is composed of a shell derived from a naturally occurring molecule called latency associated peptide (LAP). LAP forms a shell around the drug and is therefore protecting the drug from degradation within the body. The shell is opened through an enzyme-sensitive cleavage site. The enzymes that can open the shell are found at sites of inflammation particularly in joints affected by arthritis. The shell is therefore only opened and it?s contents released at the sites of disease.
This technology has many advantages over current biological drugs as it targets the release of the drug only to sites of disease thus preventing side effects, and the drug can be used in small doses. In this study we will produce and purify sufficient material of different forms of the shell and drug that can be tested, pharmaceutically assessed, and compared in a model of arthritis. In this way, we will obtain data that is essential to allow us bring this novel technology to clinical trials in humans. The success of this project will enable us to expand the use of this technology to other diseases that have a destructive/inflammatory component such as Crohn?s disease, multiple sclerosis and atherosclerosis.

To enable targeting of cytokines and other therapeutic molecules to sites of disease, we have developed a novel platform technology that harnesses the pathological process to release the therapeutic moiety in situ and provides for longer half-life. We built a stable ?shell? by fusing the latency associated peptide precursor part of transforming growth factor beta, through a linker with a matrix metalloproteinase- or aggrecanase-sensitive site (thus targeting release/activation to inflammatory sites) to a therapeutic cytokine (IFN beta) for arthritis treatment. In this study we will express and biochemically purify sufficient recombinant protein to provide data on pharmacokinetics, pharmacodynamics, immunogenicity, toxicology and therapeutic efficacy in an arthritis model. This work is essential to produce preclinical data and bring this technology to the level of a phase I/II clinical trial.