Abstract
Cerebral dopamine neurotrophic factor (CDNF) belongs to a newly discovered family of evolutionarily conserved neurotrophic factors. We demonstrate for the first time a therapeutic effect of CDNF in a unilateral 6-hydroxydopamine (6-OHDA) lesion model of Parkinson’s disease in marmoset monkeys. Furthermore, we tested the impact of high chronic doses of human recombinant CDNF on unlesioned monkeys and analyzed the amino acid sequence of marmoset CDNF. The severity of 6-OHDA lesions and treatment effects were monitored in vivo using 123I-FP-CIT (DaTSCAN) SPECT. Quantitative analysis of 123I-FP-CIT SPECT showed a significant increase of dopamine transporter binding activity in lesioned animals treated with CDNF. Glial cell line-derived neurotrophic factor (GDNF), a well-characterized and potent neurotrophic factor for dopamine neurons, served as a control in a parallel comparison with CDNF. By contrast with CDNF, only single animals responded to the treatment with GDNF, but no statistical difference was observed in the GDNF group. However, increased numbers of tyrosine hydroxylase immunoreactive neurons, observed within the lesioned caudate nucleus of GDNF-treated animals, indicate a strong bioactive potential of GDNF.
Highlights
Neurotrophic factors are considered potent candidates for the disease modifying treatment of neurodegenerative disorders such as Parkinson’s disease (PD)
These results indicate potential immunogenicity of Cerebral dopamine neurotrophic factor (CDNF) in single animals when administered in high doses
Semiquantitative analysis of CDNF-ir tissue distribution, revealed that CDNF-ir was completely absent in a single high-dose CDNF animal (S2 Fig, Table 1, animal # 13685) and this might explain the absence of histopathology in this particular animal
Summary
The aim of the study was to test the therapeutic efficacy of CDNF and to compare it with GDNF in a neurorestorative treatment approach
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