Cannabidiol improves the welfare and survival of Dravet syndrome mice
Abstract number :
2.263
Submission category :
7. Antiepileptic Drugs / 7A. Animal Studies
Year :
2017
Submission ID :
345732
Source :
www.aesnet.org
Presentation date :
12/3/2017 3:07:12 PM
Published date :
Nov 20, 2017, 11:02 AM
Authors :
Pabitra Hriday Patra, School of Pharmacy, University of Reading; Alister McNeish, School of Pharmacy, University of Reading; Claire Michelle Williams, School of Psychology & Clinical Language Sciences, University of Reading; Ben Jason Whalley, GW Research
Rationale: Dravet syndrome is a severe, pediatric form of myoclonic epilepsy in which seizures are largely refractory to treatment and where the presently available medications do not always offer satisfactory control of symptoms. Therefore, a combination of antiepileptic drugs (valproate, clobazam, stiripentol) are generally used (J Child Neurol 2004;19:516-521; Expert Opin Investig Drugs 2005;14(7):905-911; Can J Neurol Sci 2016;43[suppl 3]:S13-S18). The present study was designed to assess the therapeutic efficacy of cannabidiol (CBD) in improving the survivability and welfare of a mouse model of Dravet syndrome (Scn1a-/-). Methods: For this, Scn1a-/- mice were injected subcutaneously twice daily with Purified CBD (GW Research, 100 mg/kg; n=10) or vehicle (ethanol: Kolliphor® HS: 0.9% saline=2:1:17; n=10) from postnatal day 8 (P8) onwards until P25 or death (whichever was earlier). Similarly, wildtype littermates (Scn1a+/+) were also treated with Purified CBD (100 mg/kg, n=10) or vehicle (n=10). The dose of CBD used was calculated, by adjustment for mouse metabolism (conversion factor: 0.08) to be equivalent to 8mg/kg and so within the therapeutic range reported in human trials. A twice daily, standardized welfare check was conducted throughout the entire study to generate a neonatal welfare score, as well as assessment of natural activity, reflex/response to touch, orbital tightening, and body condition score. Results: No detrimental effects of CBD were observed upon weight gain or welfare scores among the Scn1a+/+ (p>0.05) animals, and all survived until the end of the study (P25).CBD had no effect on the weight gain of Scn1a-/- (p>0.05). It also significantly improved the neonatal welfare score (p < 0.05), natural activity (p < 0.05), response to touch (p < 0.05), orbital tightening (p < 0.05), and body condition score (p < 0.01) of Scn1a-/- animals when compared to vehicle treated animals. Furthermore, CBD significantly prolonged the median survival of Scn1a-/- animals to 16.25 days, whereas the median life span of vehicle-treated mice reached 15.5 days (p < 0.01). Conclusions: The present study showed a beneficial effect of CBD treatment upon the welfare of Dravet syndrome mice, and it is also the first to show a significant effect of an antiepileptic drug treatment upon the survivability of a mouse model of Dravet syndrome. Funding: Funded by GW Research Ltd
Antiepileptic Drugs