On October 15th, 2010, new research on cystinuria was featured on the cover of one of the world’s top academic research journals, Science. The publication, available online, describes the detailed study of cystine crystalization. This unprecedented understanding of the process by which cystine aggregates (partially illustrated in Science‘s online supplemental video material) allowed the researchers to rationally consider, identify, and test a chemical inhibitor of cystine crystal growth named cystine dimethyl ester (CDME). The group’s findings are a significant leap forward in the effort to prevent cystine kidney stones.
The story has been well-covered in an article appearing in the American Chemical Society’s Chemical and Engineering Newsand by a press release from the research group’s institution, New York University.
The announcement demonstrating the use of CDME to inhibit cystine crystal growth is exciting both to the research, medical, and patient communities. Indeed, this new research has shown that CDME is effective in a synthetic environment, making it a potential candidate for use in treating cystine stone formers. However, the road from lab science to pharmaceutical success is a long one, and some discussion of perspective is warranted.
At this stage, this research is essentially a proof of principle demonstrating the feasibility of chemically inhibiting cystine stone growth. A number of complex issues must be investigated before we can begin thinking of this chemical (CDME) or any chemical identified via this novel approach as yielding a viable treatment for cystinuria. Some interrelated key questions, common to all pharmaceutical development, will be focal points of continuing CDME research:
- Drug targeting: How much, if any, CDME would enter the urine, unchanged by human metabolism, where it can potentially inhibit cystine crystal growth?
- Drug efficacy: Are the cystine crystal growth properties observed in the synthetic system (in the “test tube”) applicable in real human being? If so, what range of urinary CDME concentration might be necessary for effective crystal inhibition?
- Toxicity and side effects: Would the prescribed doses necessary to deliver the effective amount of CDME to the urine be well tolerated by patients?
These questions need to be methodically addressed, and that process can require years of research. The good news is that researchers are actively working to get answers. Whether or not CDME has what it takes to be a viable candidate for pharmaceutical consideration is not yet known. However, the newly described method of identifying chemicals which have the ability, at least in the test tube, to inhibit cystine crystallization, opens a pipeline for the identification of additional candidates, increasing the chance of long-term success!