# Innovative therapeutic strategies to support elimination of river blindness

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $805,271

## Abstract

Abstract
Onchocerciasis (river blindness) is a major (vector-borne) neglected tropical disease caused by Onchocerca
volvulus and proposed by the World Health Organization for elimination of transmission (EOT) by 2030.
Currently, national control programs attempt to achieve EOT with mass drug administration (MDA) of ivermectin
(IVM) to individuals aged ≥5 years over prolonged periods. IVM is microfilaricidal (kills the microfilariae, mf). By
2013, only a 31% reduction in mf prevalence was achieved since MDA with IVM began in the early 1990’s,
making it clear that EOT using IVM alone would not be reached. The 2018 approval of moxidectin (MOX) for
treatment of individuals aged ≥12 years was a significant milestone in enhancing the prospects of achieving
EOT. However, as MOX is deemed to be mainly microfilaricidal (but see below), it will likely not be sufficient to
meet EOT by 2030 in all endemic areas. Therefore, the development of new drugs and alternative treatment
regimens to achieve onchocerciasis EOT is a pressing need.
 We propose to develop novel drugs and treatment regimens for facilitating sustained elimination of human
onchocerciasis, based on our significant progress on: a) identification of filarial hit drugs with macrofilaricidal
activity and their putative targets; b) demonstration that in vitro, MOX, a candidate MDA drug and emodepside
(EMO), a macrofilaricidal repurposed drug under clinical development, target the early stages of worm
development and could consequently prevent or reduce the establishment of adult worms (defined as having
prophylactic potential); and c) transmission dynamics modelling incorporating prophylactic regimens with IVM or
MOX that has already indicated that bi-annual or quarterly MOX MDA would greatly help accelerate WHO’s
elimination goals compared to IVM.
 Our proposed aims build on the substantial progress we have thus far made and comprise: i) rationally
designing novel macrofilaricidal drug candidates via medicinal chemistry optimization of known HIV-aspartic
protease inhibitors (ritonavir, lopinavir, nelfinavir) that are active against 3 filarial species in vitro and in vivo;
ii) evaluating in parallel, in vivo, the prophylactic potential of MOX and EMO (selected based on promising in
vitro results and known PK and PD profiles in humans), and iii) evaluating innovative combination treatment
approaches in vivo (using well-established filariasis animal models) as well as in silico by undertaking
mathematical modelling to identify which suites of interventions would have the greatest potential to accelerate
and protect onchocerciasis EOT in Africa.
By the end of the project, we anticipate to have developed novel macrofilaricidal drug candidates which target
one or more aspartic proteases for advanced preclinical studies and to have identified pioneering treatment
regimens through prophylaxis that will augment the critically needed complementary tools for developing new
integrated therapeutic strategies f...

## Key facts

- **NIH application ID:** 10927441
- **Project number:** 5R01AI174587-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** James W Janetka
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $805,271
- **Award type:** 5
- **Project period:** 2023-09-11 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10927441

## Citation

> US National Institutes of Health, RePORTER application 10927441, Innovative therapeutic strategies to support elimination of river blindness (5R01AI174587-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10927441. Licensed CC0.

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