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Innate immune responses to S. neurona

Updated: Oct 19, 2023


The purpose of a research experiment is to answer a question or questions. One should design the experiement to remove as much ambiguity as possible and often the results will lead to more avenues of investigation. And that is how it is with EPM (equine protozoal myeloencephalitis) research. Our more than 25 years of S. neurona research led us from EPM to polyneuritis.


In the early 2000's Pathogenes worked with two drug companies to test the effectiveness of their drugs to prevent EPM. Over 70 horses were used in multiple challenge experiments, unfortunately neither of the drug companies published the results. In both drugs tested, Marquis and Protozil, horses that received drug showed more neurologic signs that the control horses. Of course, we presented our results at the EPM society meetings. What was the significance of the signs we were seeing in experimentally challenged horses that had been given anti-protozoal drugs? Signs were related to inflammation.


In 2003 the common explanation was that "parasite" die off was eliciting the signs. But the most attractive hypothesis to the companies was the Trojan Horse infection model was too "harsh" and may not recapitulate what would happen with an oocyst challenge. Finally in 2017 a paper reported a killed S. neurona vaccination failed to prevent neurologic signs in an oocyst challenge model. The preponderence of vaccinated horses showed neurologic signs with the oocyst challenge! When the authors drill down on these observations I beleive they will also look at polyneuritis and innate immune resonses to acute parasite infections.


How about the question of preventing EPM with drugs? In one case, we pre-treated for over 100 days (10 mg/kg daily) and the treated horses showed the most signs!! How could it be explained?


I was able to publish the results from 6 of the control horses— the most the companies would allow at the time—I called it Early Signs of Equine Protozoal Myeloencephalitis. It is important to note the horses did develop EPM, upper motor neuron signs and ataxia associated with the infecitons, after 90 days. What was most perplexing was observing the lower motor neuron signs that occured first. Often starting at day 10, the signs were present before ataxia in all horses—and were apparent in sequential order! The sequence was the same in every horse but not the day signs first started...we published the observation for 6 horses, but it was the same for over 70 animals. The order of appearance in all horses perplexes me.


We first noticed weakness, stumbling, dropping feed and an abnormal tail carriage. The animal care takers noticed a change in behavior, drooling and facial paresis. A loss of pecking order in the herd was noticed by everyone feeding the horses. These signs were followed by cranial nerve deficits, muscle atrophy and then lameness. Lameness and ataxia were the last signs, the earlier signs had been present long before the classic "EPM" signs.


Our research led us to investigating polyneuritis and the untreatable polyneuritis equi and the unmet need to bring an effective treatment to the equine community for PNE. What we understand is that oocyst challenge or field infections lead to an innate immune response in the horse. That innate response leads to an increase in acute phase proteins like C-reactive protien (CRP). CRP is upregulated in acute infection and increases cytokines including cytokine IL6. IL6 can also increase CRP and this can lead to a dysregulated disease conditions including polyneuritis. We investigated serum amyloid A and found no association with acute EPM. l If we can break the self-perpetuating dysregulated inflammatory response we can control the clinical signs and prevent disease progressing to polyneuritis equi.


Please help us by using the new submission form, fill out the signs associated with PNE that you observe and check the box indicating you may have interest in enrolling your horse in our field studies.




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