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The Scientific Basis for Chelation: Animal Studies and Lead Chelation

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Abstract

This presentation summarizes several of the rodent and non-human studies that we have conducted to help inform the efficacy and clinical utility of succimer (meso-2,3-dimercaptosuccincinic acid) chelation treatment. We address the following questions: (1) What is the extent of body lead, and in particular brain lead reduction with chelation, and do reductions in blood lead accurately reflect reductions in brain lead? (2) Can succimer treatment alleviate the neurobehavioral impacts of lead poisoning? And (3) does succimer treatment, in the absence of lead poisoning, produce neurobehavioral deficits? Results from our studies in juvenile primates show that succimer treatment is effective at accelerating the elimination of lead from the body, but chelation was only marginally better than the complete cessation of lead exposure alone. Studies in lead-exposed adult primates treated with a single 19-day course of succimer showed that chelation did not measurably reduce brain lead levels compared to vehicle-treated controls. A follow-up study in rodents that underwent one or two 21-day courses of succimer treatment showed that chelation significantly reduced brain lead levels, and that two courses of succimer were significantly more efficacious at reducing brain lead levels than one. In both the primate and rodent studies, reductions in blood lead levels were a relatively poor predictor of reductions in brain lead levels. Our studies in rodents demonstrated that it is possible for succimer chelation therapy to alleviate certain types of lead-induced behavioral/cognitive dysfunction, suggesting that if a succimer treatment protocol that produced a substantial reduction of brain lead levels could be identified for humans, a functional benefit might be derived. Finally, we also found that succimer treatment produced lasting adverse neurobehavioral effects when administered to non-lead-exposed rodents, highlighting the potential risks of administering succimer or other metal-chelating agents to children who do not have elevated tissue lead levels. It is of significant concern that this type of therapy has been advocated for treating autism.

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Acknowledgments

We are grateful to the many individuals who contributed to the research that provided the foundation for much of what we know about the efficacy and underlying mechanisms of lead chelation therapy in humans and animals models. In particular, we thank L. Bayer, S. Beaudin, J. Cremin, M. Kuypers, N. Laughlin, M. Luck, D. Stangle, M. Strawderman, and D. Woolard for their significant contributions to the studies presented here. Funding for the original studies presented here was provided by the National Institutes of Health (R01 ES06918, ES07535, ES07457, ES07457, ES05950, and DK0715827, and F32 ES05870).

ATSDR Disclaimer

This publication was supported by the cooperative agreement award number 1U61TS000117-04 from the Agency for Toxic Substances and Disease Registry (ATSDR). Its contents are the responsibility of the authors and do not necessarily represent the official views of the Agency for Toxic Substances and Disease Registry (ATSDR).

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Conflict delineations

For the work under consideration for publication, Dr. Smith received an honorarium and reimbursement for travel through the ACMT/ATSDR Cooperative Agreement. Dr. Strupp has no conflicts.

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Authors and Affiliations

  1. Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, CA, USA

    Donald Smith

  2. Division of Nutritional Sciences and Department of Psychology, Cornell University, Ithaca, NY, USA

    Barbara J. Strupp

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  1. Donald Smith
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  2. Barbara J. Strupp
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Correspondence to Donald Smith.

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Smith, D., Strupp, B.J. The Scientific Basis for Chelation: Animal Studies and Lead Chelation. J. Med. Toxicol. 9, 326–338 (2013). https://doi.org/10.1007/s13181-013-0339-2

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