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The Search for Effective Treatments for Canine Inflammatory Brain Disease

February 7, 2022

Disease Summary

Necrotizing meningoencephalitis (NME) is an autoimmune disease that causes severe inflammation to develop within the brain. The disease was first characterized in the 1980s and is frequently seen in small breed dogs such as the Maltese, Chihuahua, Yorkshire Terrier, Pekingese, and French Bulldog. The most common dog breed afflicted by NME is the Pug, with the disease accounting for 69-81% of all intracranial conditions in the breed, leading to the disease commonly being referred to as Pug Dog Encephalitis.

Necrotizing meningoencephalitis in the Pug is unfortunately a disease with an early age of onset, with Pugs most commonly becoming symptomatic between 1.5 and 2.5 years of age. These symptoms are often severe and can include lethargy, behavioral changes, seizures, circling, and visual deficits. These symptoms typically don’t arise until advanced inflammation has already developed within the brain, at which point effective treatment options for the disease are extremely limited. Most Pugs will continue to have disease progression regardless of treatment, with the longest survival time being no more than 6-9 months following diagnosis. Many Pugs don’t survive past the first several days to weeks after diagnosis.

Diagnosis

The ability to diagnose NME in dogs is dependent on imaging of the brain via MRI and sampling of the spinal fluid to identify changes indicative of NME. The trigger to consider these advanced diagnostics is reliant on the recognition of symptoms consistent with NME, which is often already at a point where there are limited treatment options. This raises the question of how can NME be diagnosed at an earlier point in these dogs to allow for a greater opportunity to be able to provide effective therapy.

Previous studies on NME in Pugs have demonstrated a genetic component of the disease. This finding has allowed for the development of a diagnostic test that is now available and can be used to determine a dog’s risk of developing NME (i.e. low, medium, and high risk). This test can be performed when dogs are young and before the average age of onset of NME. Even though this genetic risk information is helpful in identifying Pugs that are in danger of developing NME, it does not solve the issue that the trigger for pursuing the advanced diagnostics needed to diagnose NME doesn’t occur until after severe inflammation has already developed within the brain.

Ethos Discovery Study – NME in Pugs

In 2019 Ethos Discovery elected to launch a scientific priority within neuroinflammatory disease. There were two overarching goals to this decision: 1) identify symptoms in Pugs that are high risk for NME that could be used to diagnose the disease earlier; 2) find new treatment options that will provide improved responses and long-term survival times.

As a first step in this process, Ethos Discovery convened a ‘Pug Clinic’ in 2020 where 40 pugs underwent neurologic evaluation and genetic testing for NME. These pugs also had blood testing performed to measure for markers of inflammation. This led to the hypothesis that dogs at genetic risk for NME have underlying altered inflammatory mechanisms which ultimately lead to the development of the severe brain inflammation associated with the disease. This supports the theory that an effective treatment for NME might be one that is aimed at correcting these altered states of inflammation; however, in order for such a therapy to be effective, we must still identify a solution on how to diagnose the disease earlier at a time where such a therapy has a better chance of being effective.

In 2021 Ethos Discovery held a second Pug Clinic where another 36 Pugs underwent neurologic examinations and genetic risk testing for NME. From this clinic, a possible early clinical phenotype (i.e. combination of symptoms) of NME was identified which may allow for the disease to be diagnosed at an earlier point when the inflammation in the brain is less severe than when it is traditionally diagnosed, opening for the opportunity to introduce treatment options that could reduce the severity of the disease as it develops or even potentially prevent the disease altogether.

Possible Course of Treatment Identified

A possible inflammatory-mediating treatment that Ethos Discovery has identified for the treatment of NME in dogs is the administration of mesenchymal stem cells. These cells can be harvested from fat tissue and have the ability to reregulate the mechanisms that control the inflammatory process, thereby potentially altering the abnormalities that lead to the severe brain inflammation associated with NME. Ethos Discovery has now launched its third study in Pug NME in which the treatment with stem cells is being investigated in Pugs at genetic risk for NME and are showing the earlier symptoms of the disease identified in the second pug clinic.

Through these efforts Ethos Discovery hopes that NME will become a disease that no longer carries such a devastating prognosis and is instead associated with the ability for early diagnosis and preventative treatment options. We are conducting these trials in collaboration with human research groups who seek to use this data to support similar clinical trials in humans with diseases that behave similarly to NME, such as multiple sclerosis.