In 2013 ISMRD and the National MPS Society offered a Partnership Grant for mucolipidosis II/III. The grant is $20,000 for each year of the two years. Following a global request for proposals which were reviewed by a committee comprised of members from our respective Scientific Advisory Committees, the grant was awarded December 2013 to Dr. Heather Flanagan-Steet at the Complex Carbohydrate Research Center at the University of Georgia. We are grateful to the National MPS Society for their work with ISMRD, ensuring the success of this endeavor.
Below is the abstract from the project that was accepted for funding.
“Investigating the role of cathepsin proteases in ML-II cardiac pathology”
Heart valve defects represent a life threatening but poorly understood symptom of ML disease. Recent work in our ML-II zebrafish model has provided new information on why the valves don’t form or function properly. Our earlier work on cartilage defects in this model identified the enzyme, cathepsin K, as a central player in the disease process. Inhibition of cathepsin K in the ML-II background resulted in improved cartilage development, suggesting a new therapeutic strategy for ML disease. Since the development of heart valves and cartilage share many common features, it is likely that cathepsin K also contributes to ML heart valve disease. We propose to use inhibitors of cathepsin K (and another related enzyme cathepsin L) to ask whether they reverse the heart valve defects present in ML-II zebrafish. At least one cathepsin K inhibitor, odanacatib, recently passed Phase III clinical trials for the treatment of osteoporosis and is expected to be available in 2014. Our proposed work may uncover a new opportunity to treat ML valve disease with these inhibitors.