Cocaine abuse is among the most pressing health and sociological problems confronting developed nations the world over. In the U.S., thousands of new users are added each and each year a large proportion die from overdose of other toxic influences. The effects on the unborn can be especially tragic. Those addicted to cocaine represent the financial and social deterioration that this drug can inflict. Significantly, abuse is detrimental not only to the well-being of the individual, but also escalates to degrade the infrastructure of society. Of particular concern is the link between intravenous cocaine administration and the spread of AIDS. The biochemistry of the action of cocaine is complex having perhaps the most unique and powerful reinforcing properties of any drug. While a number of pharmaceuticals have been evaluated, none have proven to be truly effective. Hence, there remains no concrete medical solution to the cocaine problem and it has become obvious that alternative avenues must be explored. One such approach invokes immunological strategies for the direct treatment of cocaine abuse and addiction in preventative or rehabilitative contexts. In this way, social programs would be bolstered by an objective scientific foundation. This proposal specifically delineates aspects of the chemistry, immunochemistry, and immunology necessary for the implementation of immunopharmacological protocols in the abatement of cocaine abuse. The program encompasses synthesis of haptens and reagents, monoclonal antibodies (mAbs) that bind cocaine with high affinity and specificity, catalytic mAbs that degrade cocaine, development of noncatalytic and catalytic vaccine designs, human anti-cocaine mAbs derived from combinatorial libraries, and sophisticated animal behavioral paradigms for testing all therapies. Details of preliminary results and future directions are provided.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA008590-07
Application #
6175715
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Kline, Richard
Project Start
1994-01-01
Project End
2001-08-31
Budget Start
2000-06-01
Budget End
2001-08-31
Support Year
7
Fiscal Year
2000
Total Cost
$378,513
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Kimishima, Atsushi; Olson, Margaret E; Janda, Kim D (2018) Investigations into the efficacy of multi-component cocaine vaccines. Bioorg Med Chem Lett 28:2779-2783
Bremer, Paul T; Janda, Kim D (2017) Conjugate Vaccine Immunotherapy for Substance Use Disorder. Pharmacol Rev 69:298-315
Anraku, Kensaku; Sato, Shun; Jacob, Nicholas T et al. (2017) The design and synthesis of an ?-Gal trisaccharide epitope that provides a highly specific anti-Gal immune response. Org Biomol Chem 15:2979-2992
Wenthur, Cody J; Cai, Xiaoqing; Ellis, Beverly A et al. (2017) Augmenting the efficacy of anti-cocaine catalytic antibodies through chimeric hapten design and combinatorial vaccination. Bioorg Med Chem Lett 27:3666-3668
Jacob, NIcholas T; Anraku, Kensaku; Kimishima, Atsushi et al. (2017) A bioconjugate leveraging xenoreactive antibodies to alleviate cocaine-induced behavior. Chem Commun (Camb) 53:8156-8159
Kimishima, Atsushi; Wenthur, Cody J; Eubanks, Lisa M et al. (2016) Cocaine Vaccine Development: Evaluation of Carrier and Adjuvant Combinations That Activate Multiple Toll-Like Receptors. Mol Pharm 13:3884-3890
Zhou, Bin; Eubanks, Lisa M; Jacob, Nicholas T et al. (2016) Studies towards the improvement of an anti-cocaine monoclonal antibody for treatment of acute overdose. Bioorg Med Chem Lett 26:5078-5081
Lockner, Jonathan W; Eubanks, Lisa M; Choi, Jennifer L et al. (2015) Flagellin as carrier and adjuvant in cocaine vaccine development. Mol Pharm 12:653-62
Collins, K C; Schlosburg, J E; Lockner, J W et al. (2014) Lipid tucaresol as an adjuvant for methamphetamine vaccine development. Chem Commun (Camb) 50:4079-81
Collins, Karen C; Janda, Kim D (2014) Investigating hapten clustering as a strategy to enhance vaccines against drugs of abuse. Bioconjug Chem 25:593-600

Showing the most recent 10 out of 42 publications