Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson’s Disease

• Published in: PloS one Vol. 11; no. 2; p. e0149776
• Main Authors: Garea-Rodríguez, Enrique, Eesmaa, Ave, Lindholm, Päivi, Schlumbohm, Christina, König, Jessica, Meller, Birgit, Krieglstein, Kerstin, Helms, Gunther, Saarma, Mart, Fuchs, Eberhard
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.02.2016; Public Library of Science (PLoS)
• Subjects: 6-Hydroxydopamine; Amino acid sequence; Amino acids; Anatomy & physiology; Animals; Annan fysik; Basic Medicine; Biology and life sciences; Biomedical Laboratory Science/Technology; Biomedicinsk laboratorievetenskap/teknologi; Biotechnology; Brain; Callithrix; Care and treatment; Caudate nucleus; Comparative analysis; Disease Models, Animal; Dopamine; Dopamine transporter; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Endoplasmic reticulum; Farmakologi och toxikologi; Fysik; Gene therapy; Genetic aspects; Glial cell line-derived neurotrophic factor; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Hydroxylase; Iodine; Laboratories; Lesions; Magnetic Resonance Imaging; Medical and Health Sciences; Medical Biotechnology; Medical imaging; Medicin och hälsovetenskap; Medicine and Health Sciences; Medicinsk bioteknologi; Medicinska och farmaceutiska grundvetenskaper; Monkeys; Monkeys & apes; Natural Sciences; Naturvetenskap; Nerve Growth Factors - metabolism; Neurobiology; Neurodegeneration; Neuronal-glial interactions; Neurons; Neurosciences; Neurotrophic factors; Neurotrophins; Other Physics Topics; Oxidopamine - pharmacology; Parkinson disease; Parkinson Disease - metabolism; Parkinson's disease; Pharmacology and Toxicology; Physical Sciences; Physiological aspects; Physiology; Proteins; Quantitative analysis; Research and Analysis Methods; Rodents; Single photon emission computed tomography; Tomography, Emission-Computed, Single-Photon; Tyrosine; Tyrosine 3-monooxygenase; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0149776

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.