Stiftung Tierärztliche Hochschule Hannover (TiHo)TiHo eLib

miR-134 : a new therapeutic target for drug-resistant idiopathic epilepsy in dogs?

Current antiseizure drugs (ASD) provide symptomatic control of seizures
in only two-thirds of patients and do not change the underlying
pathophysiology. Recently, microRNAs (miR) have emerged as potential
novel targets for seizure control and disease-modification in drugresistant
epilepsy. miR-134 is up-regulated in rodents after prolonged
or repeated seizures and in brain tissue form humans with drugresistant
temporal lobe epilepsy. MicroRNAs can be specifically
targeted using antisense oligonucleotides and inhibiting miR-134 has
shown potent and long-lasting anticonvulsant and neuroprotective
effects in rodent epilepsy models. We aim of to assess miR-134 as a
circulating biomarker of drug-resistant epilepsy in dogs. Plasma samples
from seven healthy dogs and 14 dogs with a tier II confidence
level for idiopathic epilepsy (IE) were used. Seven IE dogs were
responsive to ASD and seven were drug-resistant (less than 50%
reduction of seizures despite at least two ASD). RNA was extracted
using the miRCURY RNA isolation kit for biofluids (Exiqon). Levels of
miR-134 were assessed by individual Taqman miRNA by RT-qPCR on
QuantStudio 12 K Flex PCR system and expressed relative to miR-16.
ANOVA with post hoc test was used for groups comparison. Results
revealed plasma levels of miR-134 were significantly higher
(p=0.0034) in dogs with drug-resistant epilepsy compared to controls
and also considerably higher than in dogs responsive to ASD. This
confirms that changes in miR-134 expression are present in canine IE
and supports miR-134 as biomarker of drug-resistant epilepsy in
dogs and as an interesting therapeutic target for seizure control and
disease-modification in drug-resistant cases.


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