The ultimate goal of our research and development program in multiple sclerosis (MS) is to develop a novel MS drug that targets CD24, a GPI-anchored surface glycoprotein that served as a critical checkpoint for MS pathogenesis. During our previous phase I study, we have produced a fusion protein between CD24extracellular domain and the Fcmu and showed that the fusion protein has significant effect on the EAE clinical score even when applied after the onset of disease. Moreover, the fusion protein prevented relapse of EAE in the relapsing model. These results prove the concept of our phase I study and form the basis for the phase II study proposed here. During the phase II study, we will produce GMP grade human CD24Fcmufusion protein that should have no immunogenicity in the human and will test their pharmacokinetic, stability and toxicity.
Our specific aim 1 is to produce a human version of CD24Fcmu fusion protein. We will generate cell lines that produce high levels of CD24Fcmu, and select outside vendor for production of a large quantity of the fusion protein for our pre-clinical testing for IND filing.
Specific aim 2 is to conduct in vitro drug compound stability assay and pre-clinical pharmacokinetic studies for human CD24Fcmu.
Specific aim 3 is to conduct pre-clinical safety/toxicity testing of human CD24Fcmu. Our proposed studies will provide much needed pre-clinical data for the IND-filing for phase I clinical trial in MS patients. ? ?
|Motari, Edwin; Zheng, Xincheng; Su, Xiaodan et al. (2009) Analysis of Recombinant CD24 Glycans by MALDI-TOF-MS Reveals Prevalence of Sialyl-T Antigen. Am J Biomed Sci 1:1-11|