# Diethylcarbamazine, Emodepside and SLO-1 K Channels of Filaria

> **NIH NIH R21** · IOWA STATE UNIVERSITY · 2020 · $184,559

## Abstract

Project Summary
Filariasis is a group of neglected tropical diseases produced by infection with microfilaria of Clade
III parasitic nematodes that ae transmitted by biting insects. River Blindness caused by
Onchocerca volvulus, and Lymphatic Filariasis produced by Brugia malayi are examples of these
diseases. River Blindness is caused by parasites that produce scaring of the cornea as well as
severe itching and dermatitis; it infects 17 million people in West and Central Africa. Lymphatic
filariasis is a debilitating and disfiguring disease, which occurs in 120 million people worldwide.
Control of these nematode parasites relies on a small number of anthelmintic drugs, which have
a limited spectrum of action. There are no practical macrofilaricides, which kill the adult parasites
in the host; and there are concerns that mass microfilaricide chemotherapy will lead to the
development of resistance.
Diethylcarbamazine is a mainstay for the treatment of lymphatic filariasis in most parts of the
world, except in areas where onchocerciasis is present because it is contra-indicated by risks of
blindness. It produces rapid clearance of microfilaria and causes ~40% mortality of adult parasites
(macrofilaricide). It is striking however, that 68 years after its introduction, we have no proven
understanding of the molecular mechanism of its action. Here, we propose to re-invigorate this
investigation by studying its effects on filarial ion-channels, including effects on SLO-1 K channels.
Emodepside is an emerging and important cyclooctadepsipeptide class of anthelmintic that also
has effects on microfilaria and adult filaria. Single emodepside treatments could allow a major
advance over existing mass drug administration (MDA) programs which require regular
treatments to kill adult parasites. One of the putative sites of action of emodepside is on nematode
SLO-1 K channels where opening of the channels inhibits motility, but it is not effective against all
filaria. Here we propose to examine filarial SLO-1 K channels as sites of action of emodepside.
Our approach will focus on Brugia malayi but we will also use include studies on Onchocerca
and human channels. We will use patch-clamp, dsRNA knock down, Worminator motility assays
and Xenopus expression to characterize the functional properties of innate SLO-1 K channels
from Brugia malayi. In
Aim #1,
we will test the hypothesis that Brugia malayi SLO-1 K
channels are the only target sites of diethylcarbamazine and emodepside. We will use
patch-clamp recordings of SLO-1 K channels from Brugia muscle cells and examine effects of
knock down of putative targets. We propose, in , to express Onchocerca, human and
Brugia SLO-1 K channels splice variants in Xenopus oocytes to test the hypothesis that
different species of filaria and human SLO-1 K channels are pharmacologically separable
using emodepside and K channel agonists.
Aim #2
The proposal is innovative, using a combination of techniques to test the effects of
...

## Key facts

- **NIH application ID:** 9930047
- **Project number:** 5R21AI138967-02
- **Recipient organization:** IOWA STATE UNIVERSITY
- **Principal Investigator:** Richard John Martin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $184,559
- **Award type:** 5
- **Project period:** 2019-05-16 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930047

## Citation

> US National Institutes of Health, RePORTER application 9930047, Diethylcarbamazine, Emodepside and SLO-1 K Channels of Filaria (5R21AI138967-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9930047. Licensed CC0.

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