Inpharma 1231 - 1 Apr 2000 Vaccinating against stroke and epilepsy An adeno-associated virus (AAV) vaccine provides protection against the neuronal death caused by stroke and status epilepticus in rats, report researchers from New Zealand and the US. 1 In this in vivo study, the researchers created a vaccine that generates autoantibodies against a specific brain protein, the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor, by subcloning murine NMDAR1 cDNA into an AAV plasmid. This was then purified to yield a high-titre recombinant virus, AAVNMDAR1. Rats were then immunised perorally with a single dose of AAVNMDAR1, a recombinant AAV vector expressing β- galactosidase (AAVlac), or no vector (controls). Protective against epilepsy . . . One month postvaccination, the researchers used the kainate model of temporal lobe epilepsy to determine the anticonvulsant and neuroprotective efficacy of AAVNMDAR1 vaccination. Rats were administered intraperitoneal injections of kainic acid 10 mg/kg. Within 10 minutes of kainic acid administration, signs of electrographic seizure activity were seen in AAVlac- treated animals and controls, with 13/17 and 6/8 animals, respectively, developing status epilepticus. Status epilepticus developed in only 2/9 AAVNMDAR1 recipients; no EEG or behavioural changes were seen in the remaining 7 animals. In addition, the AAVNMDAR1 recipients who developed status epilepticus experienced no or moderate hippocampal injury while AAVlac-treated animals and controls experienced extensive injury. . . . and in stroke Five months postvaccination, another group of rats underwent middle cerebral artery occlusion, to determine the ischaemic neuroprotective efficacy of AAVNMDAR1 vaccination. Three days postinjury, total infarct volume was significantly smaller in AAVNMDAR1 recipients, compared with AAVlac-treated animals and controls (19.6 vs 66.4 and 55.6mm 3 , respectively). An accompanying article in Science notes that as yet, it is unclear as to exactly how this strategy could be used successfully in humans. 2 However, the article acknowledges that it proved surprisingly effective in rats. 1. During MJ, et al. An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy. Science 287: 1453-1460, 25 Feb 2000. 2. Helmuth L. New stroke treatment strategy explored. Science 287: 1379-1381, 25 Feb 2000. 800763466 1 Inpharma 1 Apr 2000 No. 1231 1173-8324/10/1231-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved

Vaccinating against stroke and epilepsy

Download PDF Report

View
212
Download
0

Embed Size (px)

Citation preview

Inpharma 1231 - 1 Apr 2000

Vaccinating against stroke andepilepsy

An adeno-associated virus (AAV) vaccine providesprotection against the neuronal death caused by strokeand status epilepticus in rats, report researchers fromNew Zealand and the US.1

In this in vivo study, the researchers created a vaccinethat generates autoantibodies against a specific brainprotein, the NR1 subunit of the N-methyl-D-aspartate(NMDA) receptor, by subcloning murine NMDAR1cDNA into an AAV plasmid. This was then purified toyield a high-titre recombinant virus, AAVNMDAR1. Ratswere then immunised perorally with a single dose ofAAVNMDAR1, a recombinant AAV vector expressing β-galactosidase (AAVlac), or no vector (controls).

Protective against epilepsy . . .One month postvaccination, the researchers used the

kainate model of temporal lobe epilepsy to determinethe anticonvulsant and neuroprotective efficacy ofAAVNMDAR1 vaccination. Rats were administeredintraperitoneal injections of kainic acid 10 mg/kg.

Within 10 minutes of kainic acid administration, signsof electrographic seizure activity were seen in AAVlac-treated animals and controls, with 13/17 and 6/8animals, respectively, developing status epilepticus.Status epilepticus developed in only 2/9 AAVNMDAR1recipients; no EEG or behavioural changes were seen inthe remaining 7 animals. In addition, the AAVNMDAR1recipients who developed status epilepticusexperienced no or moderate hippocampal injury whileAAVlac-treated animals and controls experiencedextensive injury.

. . . and in strokeFive months postvaccination, another group of rats

underwent middle cerebral artery occlusion, todetermine the ischaemic neuroprotective efficacy ofAAVNMDAR1 vaccination.

Three days postinjury, total infarct volume wassignificantly smaller in AAVNMDAR1 recipients,compared with AAVlac-treated animals and controls(19.6 vs 66.4 and 55.6mm3, respectively).

An accompanying article in Science notes that as yet, itis unclear as to exactly how this strategy could be usedsuccessfully in humans.2 However, the articleacknowledges that it proved surprisingly effective inrats.1. During MJ, et al. An oral vaccine against NMDAR1 with efficacy in

experimental stroke and epilepsy. Science 287: 1453-1460, 25 Feb 2000.2. Helmuth L. New stroke treatment strategy explored. Science 287: 1379-1381, 25

Feb 2000.800763466