The future of epilepsy treatment: Focus on adeno-associated virus vector gene therapy

UNC Gene Therapy Center, Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Drug News & Perspectives (Impact Factor: 3.13). 06/2010; 23(5):281-6. DOI: 10.1358/dnp.2010.23.5.1468393
Source: PubMed


Adeno-associated virus (AAV) vectors support long-term, nontoxic gene expression in the central nervous system, and these AAV properties prove particularly applicable to the treatment of focal epilepsies, especially intractable temporal lobe epilepsy. A number of clinical studies have employed AAV vectors and to date, no known adverse effects have been directly associated with these treatments, particularly AAV serotype 2 (AAV2). Although other AAV serotypes may confer an advantage in the future, extensive studies on the inhibitory neuropeptides, galanin and neuropeptide Y, have generated enough preclinical evidence of efficacy to warrant AAV2-based clinical trials in the near future. Beyond these trials, emerging evidence suggests that AAV-mediated manipulation of adenosine can significantly impact limbic seizure activity. Thus, with appropriate nonhuman primate transduction patterns and favorable overall toxicology studies, AAV-based manipulation of adenosine could follow the AAV-neuropeptide clinical studies. Finally, recent findings using AAV capsid shuffling and directed evolution have identified a hybrid AAV vector that can selectively cross the seizure compromised blood-brain barrier and transduce cells after peripheral, intravenous administration. Thus, in the more distant future, AAV therapeutics for focal epilepsies may be delivered without any neurosurgical interventions.

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    • "NPY application exerts prominent seizure-suppressant effects in rodents in vitro and in vivo (Baraban et al., 1997; Klapstein and Colmers, 1997; Vezzani et al., 1999; Woldbye et al., 1996, 1997, 2005) and recombinant adeno-associated viral (rAAV) vector-mediated overexpression of NPY also suppresses seizures in both acute and chronic models of epilepsy (Foti et al., 2007; Noe et al., 2008, 2010; Richichi et al., 2004; Sørensen et al., 2009). Consequently , rAAV-mediated NPY gene therapy has been proposed as an alternative treatment strategy for patients suffering from intractable TLE (McCown, 2010; Riban et al., 2009). "
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