The long term objective of this proposal is to develop a diagnostic kit for monitoring nonenzymatically galactated proteins in galactose. Classical galactose is a disorder of galactose metabolism caused by a deficiency of galactose-1-phosphate uridyltransferase. The resulting severe impairment of galactose metabolism has been recognized for half a century and the frequency of this disorder is estimated to be 1 in 40,000 births. Generally, the biochemical phenotype includes elevated concentrations of galactose, galactose-l- phosphate and galactitol in tissue and body fluids. While the disease is generally fatal, treatment consisting of severe restriction of dietary galactose has proved life saving; nevertheless, most patients develop neurological abnormalities despite this diet. Earlier studies demonstrated the occurrence of elevated levels of glycated hemoglobin/albumin in galactosemia prompting the speculation that, akin to diabetes with glycated proteins, the monitoring of galactated proteins may prove useful for managing galactosemic patients. During Phase I, we will attempt to develop a monoclonal antibody probe directed to nonenzymatically galactated albumin that by standard immunological techniques will prove specific to galactated albumin. This probe will be then used in ELISA to establish its sensitivity and range of detection. Phase II efforts will focus on evaluating this ELISA in a clinical setting and optimizing its performance for the management of galactosemic patients. Phase III efforts will focus on the commercialization of this assay. Vandalia Research, Inc. is committed to manufacture, market and sell the diagnostic kit that will result from this research effort. Pediatricians and internists have long been waiting for assays to monitor galactosemic patients; a method to quantify galactated proteins may provide a viable approach for preventing or delaying many of the complications of the disease including the onset of neurological damage during childhood and post adolescent years. ? ? ?
| Frost, Leslie; Chaudhry, Muhammad; Bell, Tiffany et al. (2011) In vitro galactation of human serum albumin: analysis of the protein's galactation sites by mass spectrometry. Anal Biochem 410:248-56 |
