Home > Publications Database > Therapeutic sphingosine-1-phosphate receptor modulation by repurposing fingolimod (FTY720) leads to mitigated neuropathy and improved clinical outcome in a mouse model for Charcot-Marie-Tooth 1X disease. > print

001     278040
005     20260105131004.0
024 7 _ |a 10.1016/j.nmd.2025.105345
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024 7 _ |a 0960-8966
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024 7 _ |a 1873-2364
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037 _ _ |a DZNE-2025-00546
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Yuan, Xidi
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245 _ _ |a Therapeutic sphingosine-1-phosphate receptor modulation by repurposing fingolimod (FTY720) leads to mitigated neuropathy and improved clinical outcome in a mouse model for Charcot-Marie-Tooth 1X disease.
260 _ _ |a Amsterdam [u.a.]
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520 _ _ |a Previous studies have shown that both the innate and adaptive immune systems foster progression of neuropathy and clinical symptoms in a mouse model for Charcot-Marie-Tooth 1X disease. Here we demonstrate a possible therapeutic translation of these findings using the clinically approved sphingosine-1-phosphate receptor modulator fingolimod (FTY720) in connexin32-deficient mice mimicking Charcot-Marie-Tooth 1X disease. Treatment with FTY720 prevented an increase of CD8+ and CD4+ T-lymphocyte numbers in both femoral quadriceps nerve as well as in ventral spinal roots. While macrophages of ventral spinal roots show a similar, albeit non-significant trend, macrophages from quadriceps nerve are not reduced upon treatment. On the histopathological level, axonopathic changes were reduced in ventral spinal roots, but not in quadriceps nerves upon treatment. Electrophysiological recordings displayed improved nerve conduction parameters upon FTY720 treatment, while clinically, FTY720 treatment ameliorated distinct parameters of motor performance and grip strength. We suggest that targeting the adaptive immune system might be a pharmacological treatment option for mitigating disease burden particularly in severe cases of Charcot-Marie-Tooth 1X.
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650 _ 7 |a Axon damage
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650 _ 7 |a FTY720
|2 Other
650 _ 7 |a Fingolimod
|2 Other
650 _ 7 |a Inherited peripheral neuropathy
|2 Other
650 _ 7 |a Macrophages
|2 Other
650 _ 7 |a Myelin
|2 Other
650 _ 7 |a Neuroinflammation
|2 Other
650 _ 7 |a T-lymphocytes
|2 Other
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Fingolimod Hydrochloride: pharmacology
|2 MeSH
650 _ 2 |a Fingolimod Hydrochloride: therapeutic use
|2 MeSH
650 _ 2 |a Charcot-Marie-Tooth Disease: drug therapy
|2 MeSH
650 _ 2 |a Charcot-Marie-Tooth Disease: physiopathology
|2 MeSH
650 _ 2 |a Charcot-Marie-Tooth Disease: pathology
|2 MeSH
650 _ 2 |a Charcot-Marie-Tooth Disease: immunology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Sphingosine 1 Phosphate Receptor Modulators: pharmacology
|2 MeSH
650 _ 2 |a Sphingosine 1 Phosphate Receptor Modulators: therapeutic use
|2 MeSH
650 _ 2 |a Neural Conduction: drug effects
|2 MeSH
650 _ 2 |a Sphingosine-1-Phosphate Receptors
|2 MeSH
650 _ 2 |a Gap Junction beta-1 Protein
|2 MeSH
650 _ 2 |a Drug Repositioning
|2 MeSH
650 _ 2 |a Spinal Nerve Roots: drug effects
|2 MeSH
650 _ 2 |a Spinal Nerve Roots: pathology
|2 MeSH
650 _ 2 |a Immunosuppressive Agents: pharmacology
|2 MeSH
650 _ 2 |a Immunosuppressive Agents: therapeutic use
|2 MeSH
650 _ 2 |a Femoral Nerve: drug effects
|2 MeSH
650 _ 2 |a Femoral Nerve: pathology
|2 MeSH
650 _ 2 |a Macrophages: drug effects
|2 MeSH
650 _ 2 |a Male
|2 MeSH
700 1 _ |a Klein, Dennis
|b 1
700 1 _ |a Maier, Anna-Maria
|b 2
700 1 _ |a Martini, Rudolf
|b 3
773 _ _ |a 10.1016/j.nmd.2025.105345
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