I-Corps: Polysaccharides functionalized with metal chelators to treat low level lead poisoning

The broader impact/commercial potential of this I-Corps project is the development of a therapeutic to treat lead poisoning by reducing the levels of lead from the blood. Lead poisoning remains a major public health issue, especially in children, where the long-term cognitive and physiological consequences are long-lasting and significant. Recent research has indicated that even levels of < 5 mcg/dL have negative health effects in children, resulting in decreased academic achievement, lower IQ scores, attention-related behavior problems, antisocial behaviors, and possibly delayed puberty and decreased kidney function for children older than 12-years.

The administration of chelators, which are molecules that bind with metals to aid in their elimination, can reduce blood lead levels. However, chelation therapy is only indicated for very high blood lead levels (> 44 mcg/dL). For lower-level lead poisoning (≤ 44 mcg/dL), the benefits of traditional chelation therapy do not outweigh the risks of the side effects of the chelators themselves.

The proposed technology uses natural biomolecules to bind lead, which is biologically compatible and safer. In addition, the proposed safer heavy metal binders may have expanded use clinically to remove other toxic metals from the body, as well as environmentally to remove heavy metal environmental contaminants.

This I-Corps project is based on the development of a chemical therapeutic to bind and remove toxic metals such as lead from the blood. The proposed technology is a chemical combination of heavy metal binders (chelators) and large sugar molecules (polysaccharides). The proposed technology is designed to retain the metal binding efficacy of the chelator, while imparting compatibility to the chelator through the polysaccharide backbone.

Initial lab results confirm that the proposed binders have substantial metal-binding capacity. In addition, cell culture and preliminary animal studies suggest that the proposed technology is both biocompatible and able to more rapidly clear toxic metals from the body as compared with unmodified chelators. Commercialization of the proposed technology may improve health outcomes and reduce healthcare expenditures.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.