Treatment of methamphetamine abuse: an antibody-based immunotherapy approach

Methamphetamine is a highly addictive psychostimulant with tens of millions of abusers around the world, and currently there is no effective or approved medication for addiction to it. Monoclonal antibodies with a high affinity for methamphetamine have the potential to sequester the drug in the vascular compartment and reduce entry into the brain, acting as peripheral pharmacokinetic antagonists without inducing adverse effects on neurons. However, in order to maintain the antibodies at an effective level, repeated administration is required, which would be expensive and problematic for patient compliance. In this study, we intended to investigate whether using a recombinant adeno-associated virus-mediated gene transfer technique can be an effective approach to achieve long-term expression of anti-methamphetamine monoclonal antibodies in mouse models. We generated a recombinant adeno-associated virus vector encoding the heavy and light chains of an anti-methamphetamine monoclonal antibody, which were constructed in a single open reading frame and linked with a 2A self-processing sequence. In the context of virus-mediated gene transfer, expression of full-length and functional monoclonal antibodies was successfully demonstrated in vitro and in vivo. Further investigations on dose optimization, long-term expression, and protection from methamphetamine challenge in mouse models are ongoing.