Researchers say bump kinase inhibitors show promise in treating horses with this neurologic disease

Equine protozoal myeloencephalitis (EPM) presents a major challenge for horse owners and veterinarians. This sometimes debilitating neurologic disease, driven by the protozoan parasite Sarcocystis neurona (and occasionally Neospora hughesi), surfaced in 1964. By the early 1990s, equine practitioners identified S. neurona itself in a horse with clinical signs of EPM. Today, equine researchers have deemed EPM the most common infectious neurologic condition affecting horses in North America. Understanding and addressing the disease remains crucial for equine health.

As far as treatment, the Food and Drug Administration (FDA) has approved only three drugs for EPM, and none are 100% effective. Therefore, great opportunity exists for creating new EPM medications, and one such class of drugs currently in development is the bump kinase inhibitors or BKIs.

In this article we’ll briefly review EPM and the current FDA-approved treatments, laying the foundation for understanding BKIs and where they are in clinical development, providing a ray of hope for those caring for horses with EPM.

Brief Review of EPM

Horses ingest the sporocysts of S. neurona that infected opossums shed in their feces. The horse’s immune system either clears the parasites or they migrate to the central nervous system (CNS), most commonly the spinal cord, invading those cells and causing clinical signs of disease.

The reported seroprevalence of S. neurona in North America can be quite high, reaching 89% in some studies. If a horse is seropositive it means he was infected with S. neurona but does not necessarily exhibit signs of neurologic disease. If the immune system clears the parasite before it migrates to the CNS, the horse typically has antibodies in his bloodstream against S. neurona (i.e., remains seropositive) but shows no signs of disease.

When the horse’s immune system doesn’t clear the infection, S. neurona can essentially “land” anywhere within the CNS, causing trauma and inflammation. Clinical signs vary based on the parasite’s location but could include asymmetric muscle atrophy and weakness, incoordination (ataxia), and stumbling. The signs, which usually involve all four limbs, can be so subtle the horse might originally appear lame rather than neurologic, or he could present with severe acute signs, having difficulty standing. Other clinical signs can include head tilt, facial nerve paralysis, difficulty swallowing, and even seizures.   

Despite the high seroprevalence of 89% mentioned, prevalence of clinical disease remains extremely low at only 0.5-1%. It is unclear why most horses can successfully fight off infection with S. neurona while others cannot and instead develop clinical signs.

Current FDA-Approved Treatment Recommendations

Authors of the most recently published ACVIM Consensus Statement on treating EPM (Reed et al., 2016), report that horses should only be treated with one of the three FDA-approved medications. Although those guidelines are nearly a decade old, no new medications have become available, and the authors say the recommendations from 2016 remain relevant today