— Journal of Neuroscience publication demonstrates that
antagonizing miR-135a reduces seizures in chronic TLE model —

UTRECHT, Netherlands–(BUSINESS WIRE)–InteRNA Technologies announced today the recent publication of data from
a collaboration with University Medical Center (UMC) Utrecht in Journal
of Neuroscience showing that the downregulation of miR-135a levels
can reduce seizure activity after the onset of spontaneous recurrent
seizures (SRS) in chronic-stage Mesial Temporal Lobe Epilepsy (mTLE) in
mouse models. miR-135 is a microRNA (miRNA) known to control neuronal
morphology and synaptic function that is upregulated in neurons in the
epileptic brain. The data support the overall potential of miRNAs as a
treatment modality in complex diseases and also underscore InteRNA’s
expertise in the application of miRNAs as a new therapeutic approach.

The paper provides novel insights into the pathological mechanisms of
mTLE, which remain poorly understood to-date. In the study, it was shown
for the first time that miR-135a is significantly overexpressed in human
mTLE hippocampal samples and that the silencing of this specific miRNA
in mouse models by an antimir drastically reduces the number, severity
and time spent in seizures in the SRS stage, an advanced disease stage
where current treatments fail to induce an effect. Furthermore, novel
neuronal downstream targets of miR-135a were identified. In particular,
the role of Mef2a, an activity-dependent transcription factor regulating
synaptic strength, was investigated in closer detail. The data
demonstrated that miR-135a and Mef2a show reciprocal expression
regulation in TLE and that Mef2a is required for miR135a-induced
dendritic spine changes in neurons that might induce synaptic defects
involved in the pathomechanisms of TLE. The research paper titled,
“Antagonizing increased miR-135a levels at the chronic stage of
experimental TLE reduces spontaneous recurrent seizures” was published
in Journal of Neuroscience on April 23, 2019.

“TLE accounts for a third of all epilepsies and available treatments
lack disease-modifying effects and are ineffective in one third of all
mTLE patients,” commented Prof. Jeroen Pasterkamp, PhD, Department of
Translational Neuroscience, UMC Utrecht Brain Center. “The data from
this study indicate that targeting epilepsy-associated miRNAs has the
potential to unlock a novel therapeutic entity and provides key insights
into the disease biology of epilepsy.”

Roel Schaapveld, CEO of InteRNA added: “The published data provide
evidence that targeting a single miRNA could represent a new modality in
the epilepsy field where current treatments are solely based on ion
channel blockers that only relieve symptoms rather than provide curative
effects. We are encouraged by the results of this study that further
validate InteRNA’s proprietary miRNA platform, which has the potential
to target cancer, our primary focus, as well as other complex disease
states outside of the realm of oncology.”

About InteRNA Technologies
InteRNA is developing a pipeline
of proprietary preclinical microRNA drug candidates targeting key
processes in initiation and progression of human diseases, with a focus
on cancer. Enabled with a 3^rd generation drug delivery
formulation, these miRNA compounds can mount a coordinated anti-cancer
attack by engaging multiple signal transduction targets simultaneously.
With this approach, we address the high need for novel therapeutics with
improved efficacy and less drug resistance that benefit cancer patients.

Contacts

InteRNA Technologies
Dr. Roel Schaapveld, CEO
Phone:
+31 (0)30 253 23 86
E-mail: schaapveld@interna-technologies.com

Trophic Communications
Dr. Stephanie May or Joanne Tudorica
Phone:
+49 2388 7733 30 or +49 171 185 56 82
E-mail: may@trophic.eu
or tudorica@trophic.eu