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The Armadillo as a Model for Leprosy Nerve Function Impairment: Preventative and Therapeutic Interventions
Maria Teresa Pena1, Ramanuj Lahiri1, Gigi J Ebenezer2
1United States Department of Health and Human Services, Health Resources and Services Administration, Health Systems Bureau, National Hansen's Disease Program, Baton Rouge, LA, United States.
Leprosy causes nerve damage, leading to disability. In armadillos, 4-aminopyridine (4-AP) showed promise in improving nerve function and protecting against Mycobacterium leprae infection. This supports the armadillo as a leprosy nerve injury model.
Area of Science:
- Neuroscience
- Infectious Diseases
- Animal Models
Background:
- Leprosy, caused by Mycobacterium leprae, leads to peripheral nerve impairment (NFI), a primary cause of disability and stigma.
- Improved treatments for M. leprae-induced nerve injury are crucial, as current therapies primarily target the bacteria, not the nerve damage.
- The nine-banded armadillo (Dasypus novemcinctus) naturally develops a leprosy spectrum similar to humans, including extensive peripheral nerve involvement.
Purpose of the Study:
- To utilize advanced technologies to compare nerve function in M. leprae-infected versus uninfected armadillos.
- To establish an objective scoring system for nerve impairment in leprosy.
- To evaluate the neuroprotective potential of ethoxyquin (EQ) and 4-aminopyridine (4-AP) in M. leprae-infected armadillos.
Main Methods:
- Assessed motor nerve conduction velocity (MNCV) and compound muscle action potential (cMAP) to measure nerve impulse transmission.
- Employed ultrasonography with color Doppler imaging to detect nerve enlargement and vascularity.
- Quantified epidermal nerve fiber density (ENFD) and neuromuscular junction (NMJ) integrity as indicators of nerve damage and function.
Main Results:
- Nerve impairment in infected armadillos progressed with infection duration, allowing for an objective nerve impairment scoring system.
- Ultrasonography revealed nerve enlargement and increased vascularity in infected animals, suggesting inflammation.
- 4-AP treatment significantly improved MNCV, cMAP, and ENFD compared to untreated controls, while EQ showed minimal effects.
Conclusions:
- The armadillo serves as a valuable preclinical model for studying M. leprae-induced peripheral nerve injury.
- The developed assessment tools provide objective measures for nerve damage progression in leprosy.
- 4-AP demonstrates potential as a neuro-therapeutic agent for leprosy-related nerve damage, warranting further investigation.
