# Kv7.2/7.3 Activators for the Treatment of Epilepsy Disorders

> **NIH NIH U44** · KNOPP BIOSCIENCES, LLC · 2020 · $41,680

## Abstract

Project Summary
Epilepsy is the oldest known and most common serious, chronic neurological disorder that is characterized by
recurrent seizures. It currently affects 65 million people worldwide, including 2.3 million adults and nearly
470,000 children in the United States. People with epilepsy suffer from seizure-related disabilities, depression
and anxiety and have increased mortality compared to the general population. Over the last few decades there
has been considerable effort and success to bringing new anti-seizure drugs to market. Despite the availability
of several newer medications, approximately 30% of patients are treatment-resistant. Furthermore, anti-seizure
drug therapies are associated with significant adverse effects and often require careful titration to achieve
efficacy while minimizing disabling side effects.
Neuronal potassium channels play a key role in regulating neuronal activities. Kv7.1-7.5 channels are one
family of voltage-gated potassium channels critical in maintaining the resting membrane potential of excitable
cells and neuronal Kv7 channels act to dampen repetitive firing of neurons. Additional interest in Kv7.2 and
Kv7.3 channels come from the discovery of mutations in the Kv7.2 or Kv7.3 genes found to be associated with
some inherited forms of epilepsy. Thus small molecule drugs that activate the opening of Kv7.2 and Kv7.3
channels have potential to treat many neuronal hyperexcitability disorders, including epilepsy.
A recently approved anti-seizure drug, ezogabine, acts primarily by opening Kv7.2-7.5 channels with activity on
the GABAA system as well. However, in addition to tolerability issues, ezogabine use has been associated with
serious adverse effects that have limited its utility, including retinal and skin discoloration that are likely linked
to ezogabine’s chemical instability rather than its Kv7 activities.
The goal of this Knopp Biosciences program is to design and develop a Kv7.2/7.3 activator that fully realizes
the potential of this target to address the unmet medical need of treatment-resistant epilepsy patients and
difficult-to-treat generalized epilepsy syndromes. Such a compound will possess a dramatically improved
tolerability and safety profile over that of ezogabine not only via improved intrinsic chemical stability
characteristics, but also due to reduced Kv7.4 activity so as to avoid side effects that may be caused by
opening Kv7.4 channels present in blood vessels and smooth muscle. In addition, the next generation
Kv7.2/7.3 activator will remove activity on the GABAA channels. To accomplish this, Knopp has developed a
variety of in vitro screening assays using Kv7-expressing cell lines and primary neurons. These data, along
with those generated from a battery of in vitro assays testing for metabolism and drug-like properties, will be
used to select compounds for study in acute and chronic animal models of epilepsy. We will also evaluate the
tolerability of compounds in animals to identif...

## Key facts

- **NIH application ID:** 10220632
- **Project number:** 3U44NS093160-04S1
- **Recipient organization:** KNOPP BIOSCIENCES, LLC
- **Principal Investigator:** Michael Bozik
- **Activity code:** U44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $41,680
- **Award type:** 3
- **Project period:** 2020-07-22 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220632

## Citation

> US National Institutes of Health, RePORTER application 10220632, Kv7.2/7.3 Activators for the Treatment of Epilepsy Disorders (3U44NS093160-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10220632. Licensed CC0.

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