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FTY720-derivatives do not induce FTY720-like lymphopenia.

ABSTRACT: FTY720 is an immunosuppressive multiple sclerosis (MS) drug that stimulates the expression of neuroprotective brain-derived-neurotrophic-factor (BDNF). In vivo preclinical data suggest that FTY720 could be beneficial for treating Parkinson's patients, though its immunosuppressive effects might limit its efficacy. Two novel FTY720-derivatives, FTY720-C2 and FTY720-Mitoxy, also stimulate BDNF expression and enter brain like FTY720 but are not phosphorylated, suggesting they will not produce FTY720-like immunosuppression. Using FTY720 as a positive control, we measured low and high dose FTY720-derivatives, which did not stimulate FTY720-like lymphopenia or immunosuppressive signaling. These findings support the further preclinical assessment of the derivatives as potential novel Parkinson's therapies.

SUBMITTER: Segura-Ulate I

PROVIDER: S-EPMC7959251 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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FTY720-derivatives do not induce FTY720-like lymphopenia.

Segura-Ulate Ismael I Belcher Troy K TK Vidal-Martinez Guadalupe G Vargas-Medrano Javier J Perez Ruth G RG

Journal of pharmacological sciences 20170217 3

FTY720 is an immunosuppressive multiple sclerosis (MS) drug that stimulates the expression of neuroprotective brain-derived-neurotrophic-factor (BDNF). In vivo preclinical data suggest that FTY720 could be beneficial for treating Parkinson's patients, though its immunosuppressive effects might limit its efficacy. Two novel FTY720-derivatives, FTY720-C2 and FTY720-Mitoxy, also stimulate BDNF expression and enter brain like FTY720 but are not phosphorylated, suggesting they will not produce FTY720 ...[more]

PMID: 28363412

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