Key Research Findings

Acute flaccid myelitis (AFM) is a serious neurological condition that primarily affects children and is characterized by sudden onset of limb weakness or paralysis. 3 , 2 , 1 , 12 , 18 , 19 , 20 , 21 , 23 , 26 , 27 , 28 , 30 AFM cases have been increasing in the US, especially in the late summer and early fall, since 2014. 14 , 30 Research suggests that enterovirus D68 (EV-D68) is a major cause of AFM. 3 , 8 , 24 , 28 , 30 Currently, there is no FDA-approved treatment for AFM, and treatment is primarily supportive. 2 , 30 However, recent studies have shown promise for telaprevir, an FDA-approved protease inhibitor, in treating AFM. 3 Telaprevir inhibits EV-D68 replication, and early treatment in a mouse model of AFM resulted in reduced paralysis, viral titer, and apoptotic activity in muscles and spinal cords. 3 Another study investigated an isoxazole-3-carboxamide analog of pleconaril (11526092), which showed potent inhibition of EV-D68 and other enteroviruses in vitro. 4 This compound also demonstrated in vivo efficacy in a mouse model of EV-D68 infection, reducing viral load. 4 However, it was not effective in an AFM neurological infection model. 4 Further research has shown that molnupiravir and its active form, EIDD-1931, demonstrate potent antiviral activity against enterovirus infections in vitro and in vivo. 9

Treatment Summary

Telaprevir has shown promise in treating AFM in a mouse model, reducing paralysis, viral titer, and apoptotic activity in muscles and spinal cords. 3 Another potential treatment, an isoxazole-3-carboxamide analog of pleconaril (11526092), has demonstrated potent inhibition of EV-D68 and other enteroviruses in vitro, and in vivo efficacy in a mouse model of EV-D68 infection. 4 Finally, molnupiravir and its active form, EIDD-1931, hold promise as antiviral treatments for enterovirus infections. 9

Benefits and Risks

Benefit Summary

Research suggests that telaprevir and an isoxazole-3-carboxamide analog of pleconaril (11526092) may be potential treatments for AFM. 3 , 4 Molnupiravir also shows promise as a potential antiviral treatment for enterovirus infections. 9

Risk Summary

Telaprevir has been associated with toxicity at higher doses, requiring careful dosage adjustments. 3 The isoxazole-3-carboxamide analog of pleconaril (11526092) was not effective in an AFM neurological infection model. 4 Molnupiravir is not yet approved for use in humans. 9 These medications are still in development, and further research is necessary to determine their safety and efficacy.

Comparison of Studies

Commonalities

Multiple studies highlight the importance of developing antiviral drugs to combat EV-D68 and other enteroviruses. 3 , 4 , 6 , 8 , 9 , 24 These studies represent a significant step towards understanding the causes of AFM and developing effective treatments.

Differences

The studies differ in the antiviral drugs investigated, as well as the models used. 3 , 4 , 9 Moreover, all of these studies were conducted in mouse models, and further research is needed to confirm their efficacy in humans.

Consistency and Contradictions

There is a consistent finding that telaprevir and the isoxazole-3-carboxamide analog of pleconaril (11526092) show promise as potential treatments for AFM. 3 , 4 However, these medications are still under development, and further research is crucial to validate their safety and efficacy.

Real-World Application Considerations

It's important to remember that these findings are based on animal studies and need further confirmation in humans. 3 , 4 , 9 Therefore, cautious consideration is necessary before applying these treatments to human patients.

Limitations of Current Research

These studies were conducted in mouse models, and the results may not be directly transferable to humans. 3 , 4 , 9 Additionally, the sample sizes in these studies were relatively small, which may limit the generalizability of the findings.

Future Research Directions

Further research is essential to develop effective treatments for AFM. 2 Human clinical trials are needed to validate the safety and efficacy of these medications. 3 , 4 , 9 Basic research is also crucial to understand the mechanisms behind AFM and identify new therapeutic targets.

Conclusion

AFM is a serious neurological condition affecting children, and the development of effective treatments is critical. 2 While recent research shows promise for telaprevir and the isoxazole-3-carboxamide analog of pleconaril (11526092) as potential treatments for AFM, 3 , 4 further research is needed to establish their safety and efficacy.

Treatment List

Telaprevir, isoxazole-3-carboxamide analog of pleconaril, molnupiravir, IVIg, steroids, plasma exchange, nerve transfer