Canine epilepsy as a translational model?

Abstract

SUMMARYDogs with spontaneous diseases can exhibit a striking similarity in etiology, clinical manifestation, and disease course when compared to human patients. Therefore, dogs are intensely discussed as a translational model of human disease. In particular, genetic studies in selected dog breeds serve as an excellent tool to identify epilepsy disease genes. In addition, canine epilepsy is discussed as a translational platform for drug testing. On one hand, epileptic dogs might serve as an interesting model by allowing the evaluation of drug efficacy and potency under clinical conditions with a focus on chronic seizures resistant to standard medication, preventive strategies, or status epilepticus. On the other hand, several limitations need to be considered including owner-based seizure monitoring, species differences in pharmacokinetics and drug interactions, as well as cost-intensiveness. The review gives an overview on the current state of knowledge regarding the etiology, clinical manifestation, pathology, and drug response of canine epilepsy, also pointing out the urgent need for further research on specific aspects. Moreover, the putative advantages, the disadvantages, and limitations of antiepileptic drug testing in canine epilepsy are critically discussed.

Clinical Risk Factors Associated with Anti-Epileptic Drug Responsiveness in Canine Epilepsy

“…In addition to anti-epileptic drug (AED) therapy, surgical interventions are utilised to achieve seizure freedom in medically intractable cases [6]. The dog has been considered as a naturally occurring model of human epilepsy [7], [8]. There are considerable parallels in the diagnosis of human and canine epilepsy, with similarly high levels of workup, for example and the use of advanced diagnostic imaging and in limited cases, the use of electroencephalography (EEG) [9].…”

Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1

“…Aggressive breeding has resulted in a unique genetic architecture that facilitates gene discovery (1). Many breeds originate from a limited number of founder animals and the use of popular sires is a common practice.…”

“…A strong genetic background is suspected in many dog breeds with a high prevalence (4) and several genes have been discovered in both symptomatic and idiopathic epilepsy. Most of these genes represent orthologs to the corresponding human epilepsy genes, such the canine models for progressive myoclonic epilepsy, including NHLRC1 in Lafora disease (5,6) and CLN1, CLN2, ATP13A2, CLN5, CLN6, CLN8, and MFSD8 in different types of neuronal ceroid lipofuscinosis (1,7). Only two genes have been associated with idiopathic epilepsy in dogs, ADAM23 and LGI2 (8,9).…”

What New Modeling Approaches Will Help Us Identify Promising Drug Treatments?

“…This situation has changed by the recent approval of imepitoin for treatment of dogs with newly diagnosed epilepsy (see below). Furthermore, several newer AEDs, including levetiracetam, felbamate, zonisamide, topiramate, gabapentin, and pregabalin are used as addon treatment in dogs with pharmacoresistant seizures [ 64 ]. It has been tried to overcome the problem of too rapid elimination of most AEDs by dogs by using sustained-release formulations; however, sustained-release preparations developed for use in humans are not suited for dogs because of the much higher gastrointestinal passage rate in dogs (~24 h) vs. humans (~65-100 h) [ 36 , 44 ].…”