PI: Stefanie Sydlik
University: Carnegie Mellon University
No safe level of lead in the body exists, according to the CDC; yet, lead poisoning remains a significant public health concern. While policy efforts, such as removal of lead from gasoline and paint, have decreased average blood concentrations, substantial portions of the population, many of them children, still possess lower but nonetheless dangerous blood lead levels (< 5 mcg/dL). The status quo treatment for these individuals is environmental remediation of lead; however, remediation may not remove all sources of lead. Further, lead is biopersistent, with blood, soft tissue, and bone half-lives of weeks, months and decades. Thus, removing lead from the body would be highly desirable. Chelators are molecules that bind metals and are used in chelation therapy to treat metal poisoning. Unfortunately, chelators are also associated with serious side effects, limiting chelation therapy to only those patients with acutely high blood concentrations of lead (> 45 mcg/dL) where the risks of chelator side effects are mitigated by extreme lead toxicity. Therefore, there is a significant need to create biocompatible chelators that can safely treat patients with low blood levels of lead. The goal of this proposal is to functionalize safe biomolecules with a known lead chelator. The biomolecule component will mitigate the toxicity of the chelator, and its structure can be tuned for oral or intravenous administration. Ultimately, the new “biochelators” should enable the safe chelation of low levels of lead in the blood, thus preventing chronic toxicological effects of lead.