Efficacy of decoquinate against Sarcocystis neurona in cell cultures

Lindsay, David S.; Nazir, Muhammad Mudasser; Maqbool, Azhar; Ellison, Siobhan P.; Strobl, Jeannine S.

doi:10.1016/j.vetpar.2013.02.008

Cited by 15 publications

(12 citation statements)

References 23 publications

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“…In vitro testing has determined that it is effective against S. neurona at low concentrations (Lindsay et al, 2013). Decoquinate in combination with the immunomodulator levamisole has been investigated for treatment of EPM in one published study, with a very high rate of clinical improvement reported after only tendays of treatment (Ellison and Lindsay, 2012).…”

Section: Treatmentmentioning

confidence: 99%

An update on Sarcocystis neurona infections in animals and equine protozoal myeloencephalitis (EPM)

Dubey

Howe

Furr

et al. 2015

Veterinary Parasitology

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Equine protozoal myeloencephalitis (EPM) is a serious disease of horses, and its management continues to be a challenge for veterinarians. The protozoan Sarcocystis neurona is most commonly associated with EPM. S. neurona has emerged as a common cause of mortality in marine mammals, especially sea otters (Enhydra lutris). EPM-like illness has also been recorded in several other mammals, including domestic dogs and cats. This paper updates S. neurona and EPM information from the last 15 years on the advances regarding life cycle, molecular biology, epidemiology, clinical signs, diagnosis, treatment and control.

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Section: Treatmentmentioning

confidence: 99%

An update on Sarcocystis neurona infections in animals and equine protozoal myeloencephalitis (EPM)

Dubey

Howe

Furr

et al. 2015

Veterinary Parasitology

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“…Merozoites of the sixth passage of the Sn-15OP isolate were grown in African green monkey (Cercopithecus aethiops) kidney cells (CV-1[ATTC CCL-70]) American Type Culture Collection, Manassas, Virginia, separated from host cells, collected and enumerated for inoculations as previously described (Lindsay et al, 2013). The Sn-15OP isolate was isolated from the brain of an Ifnc À/À mouse fed sporocysts obtained from the feces of a naturally infected opossum from Virginia .…”

Section: Sarcocystis Neurona Culture and Preparation Of Inoculummentioning

confidence: 99%

Sarcocystis neurona–Induced Myeloencephalitis Relapse Following Anticoccidial Treatment

Hay

Witonsky

Lindsay

et al. 2019

Journal of Parasitology

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“…After in vitro cultivation of S. neurona parasites was achieved in 1991 testing of potential therapeutic compounds became possible ( Dubey et al, 1991 ). Since then, several additional compounds have been used in the treatment of EPM including: diclazuril, ponazuril, nitazoxanide and decoquinate ( Dirikolu et al, 1999 , Dirikolu et al, 2006 , MacKay et al, 2000 , Mitchell et al, 2005 , Lindsay et al, 2013 ). Both diclazuril and ponazuril are FDA-approved benzeneacetonitrile compounds related to the herbicide atrazine and are hypothesized to act by inhibiting the apicoplast (a derived non-photosynthetic plastid found in most apicomplexa) and/or mitochondrial function in the parasite ( Mitchell et al, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

“…The antiprotozoal compound decoquinate disrupts electron transport in the mitochondrial cytochrome system of apicomplexans ( Nam et al, 2011 ) and is commonly used to treat coccidiosis in livestock. Recently, decoquinate was determined to have activity against S. neurona at low concentrations in vitro ( Lindsay et al, 2013 ). Treatment of EPM using decoquinate in combination with the immunomodulator levamisole has been reported to provide significant clinical improvement after 10 days of treatment ( Ellison and Lindsay, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

“…Traditionally, inhibitory effects of compounds against S. neurona were measured by in vitro merozoite production assays patterned after an assay developed by Lindsay and Dubey in 2000 ( Lindsay and Dubey, 2000 ). These time-consuming and labor-intensive assays were used to characterize the in vitro antiprotozoal activity of the currently available EPM drugs and other compounds against S. neurona ( Lindsay and Dubey, 1999 , Lindsay and Dubey, 2000 , Lindsay et al, 2000 , Gargala et al, 2005 , Gargala et al, 2009 , Dirikolu et al, 2013 , Lindsay et al, 2013 ). Other studies used 3H-uracil incorporation ( Marsh et al, 2001 ), plaque assay ( Kruttlin et al, 2001 ), or light microscopy and TEM ( Mitchell et al, 2005 ) to describe the inhibitory effects of drugs on S. neurona .…”

Section: Introductionmentioning

confidence: 99%

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High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth

Bowden

Land

O’Connor

et al. 2018

International Journal for Parasitology: Drugs and Drug Resistan

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The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60–70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Our screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by our screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83%) have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18) of the inhibitory compounds have reported activity against dopamine receptors. We also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8 ± 12.8 ng/ml after 500 mg dose, inhibits S. neurona parasites at low concentrations (0.065 μM [0.036–0.12; 95% CI] or 21.9 ng/ml [12.1–40.3; 95% CI]). These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection.

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Efficacy of decoquinate against Sarcocystis neurona in cell cultures

Cited by 15 publications

References 23 publications

An update on Sarcocystis neurona infections in animals and equine protozoal myeloencephalitis (EPM)

An update on Sarcocystis neurona infections in animals and equine protozoal myeloencephalitis (EPM)

Sarcocystis neurona–Induced Myeloencephalitis Relapse Following Anticoccidial Treatment

High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth

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