
Abnormal iron metabolism is linked to many neurodegenerative disorders, spurring scientists to search for ways to keep iron levels in balance and to develop drugs to correct an imbalance.
Daniel Kosman, Ph.D., professor of biochemistry in the School of Medicine and Biomedical Sciences, has received a two-year, $418,363 grant from the National Institutes of Health to develop a drug aimed at an iron-based neurodegenerative disease called aceruloplasminemia.
This research complements the $1.16 million 4-year NIH grant Kosman received in June to study how iron is metabolized in cells.
Aceruloplasminemia occurs when the balance between the compartmentalization and storage of iron and the mobilization and transport of iron is disrupted. The condition is caused by a deficiency in the activity of the enzyme ceruloplasmin, which is essential for normal iron metabolism.
Kosman's research group has developed a method to produce human ceruloplasmin and to modify this protein and its yeast counterpart, Fet3p, into a form that will be stable in the bloodstream, a first requirement for any pharmacologic agent. These proteins will be furthered modified to target them to the brain.
Lynn Zeigler, senior research technician, and doctoral students Satadipta Chakraborty and Julie Spix collaborated on developing a method to produce human ceruloplasmin for these studies.
Kosman's group will test the therapeutic protein in a mouse strain genetically altered to exhibit the problems in iron metabolism observed clinically in humans. This work will be carried out in collaboration with Zena Leah Harris, M.D., a specialist in pediatric clinical care at Johns Hopkins University School of Medicine, and Jonathan D. Gitlin, M.D., professor of pediatrics and genetics at the Washington University School of Medicine.
Source: ANI
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