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Intravenous allogeneic mesenchymal stromal cell therapy in 13 Pugs with presumptive early necrotizing
Rebecca C Windsor1, Samuel Stewart1, Jennifer M Cassano2
11Ethos Discovery, San Diego, CA.
Objective:
To describe the tolerability and activity of IV allogeneic mesenchymal stromal cell (MSC) therapy in 13 Pugs with presumptive early necrotizing meningoencephalitis (NME).
Methods:
255 Pugs were screened from 2021 to 2024 for neurological examination (NE) abnormalities suggestive of early NME. All dogs received a minimum of 2 NEs spaced 2 to 4 weeks apart. An NE score (NES) was assigned at each visit. Magnetic resonance imaging, CSF analysis, and infectious disease testing was obtained in all affected Pugs. Pugs with consistent or progressive NES and MRI or CSF findings supportive of early NME were eligible for MSC therapy.
Results:
NE abnormalities prior to MSC therapy included spinal hyperesthesia (11 of 13 [85%]), paw placement deficit (11 of 13 [85%]), menace deficit (9 of 13 [69%]), obtundation (9 of 13 [69%]), seizures (7 of 13 [54%]), and ataxia (4 of 13 [31%]). The NES improved in all dogs within 24 hours of the first dose of MSC (mean improvement, 86%). Mild adverse events were noted after 3 of 30 MSC doses (10%). All 13 dogs are currently in remission (follow-up time, 5 to 43 months); 7 of 13 Pugs (54%) remained in remission after MSC therapy alone, and 6 of 13 (46%) required the addition of immunosuppressive therapy.
Conclusions:
IV allogeneic MSC administration was well tolerated and resulted in immediate clinical benefit in this small cohort of Pugs with presumptive early NME. Strategies to maintain the long-term benefits of MSC therapy require further study.
Clinical Relevance:
Immunomodulatory MSC therapy may be a potential treatment for neuroinflammatory disease in dogs. Further studies are needed to optimize long-term benefits.
Insights
Intravenous allogeneic mesenchymal stromal cell (MSC) therapy showed immediate clinical benefit and was well tolerated in Pugs with early necrotizing meningoencephalitis (NME). Further research is needed to optimize long-term remission strategies for this neuroinflammatory condition.
Area of Science:
- Veterinary Neurology
- Regenerative Medicine
- Immunology
Background:
- Necrotizing meningoencephalitis (NME) is a severe neuroinflammatory disease in Pugs.
- Early diagnosis and intervention are crucial for managing NME.
- Current treatment options for NME have limitations.
Purpose of the Study:
- To evaluate the tolerability and clinical activity of intravenous allogeneic mesenchymal stromal cell (MSC) therapy.
- To assess MSC therapy as a potential treatment for presumptive early NME in Pugs.
Main Methods:
- 13 Pugs with presumptive early NME were treated with IV allogeneic MSC therapy.
- Dogs underwent neurological examinations, MRI, and CSF analysis.
- Tolerability and clinical improvement were monitored.
Main Results:
- All dogs showed immediate improvement in neurological examination scores (mean 86%) within 24 hours of the first MSC dose.
- MSC therapy was well tolerated with mild adverse events in 10% of doses.
- 54% of Pugs remained in remission with MSC therapy alone; 46% required additional immunosuppressive therapy.
Conclusions:
- Intravenous allogeneic MSC administration is a safe and effective treatment for immediate clinical improvement in Pugs with early NME.
- Long-term remission strategies require further investigation.
- MSC therapy holds promise for treating canine neuroinflammatory diseases.
