title: Prospects of Neurotrophic Factors for Parkinson's Disease: Comparison of Protein and Gene Therapy.
abstract: Neurotrophic factors (NTFs) hold great potential as therapeutic agents in the treatment of neurodegenerative conditions, including Parkinson's disease (PD), in which the progressive loss of dopamine neurons in the substantia nigra pars compacta causes severe motor symptoms. There is extensive evidence that in preclinical animal models of PD NTFs are both neuroprotective and neurorestorative. In particular, glial cell line-derived neurotrophic factor (GDNF), neurturin (NRTN), cerebral dopamine neurotrophic factor, and mesencephalic astrocyte-derived neurotrophic factor have shown great potential to restore dopamine neurocircuitry. Although some previous clinical trials have demonstrated limited efficacy of GDNF and NRTN, there are several concerns raised with these studies. Moreover, open-label studies with GDNF as well as a study with NRTN showed clinical improvement, particularly in patients with early-stage PD. Indeed, as previous clinical trials with NTFs were associated with several technical problems, there is a great need for further investigations. In this review we discuss the emerging and existing possibilities to use NTFs as neurorestorative agents and the ways to improve their efficacy, and compare gene therapy and recombinant protein therapy approaches for restoring the dopamine circuitry in PD.
authors.affiliation: Institute of Biotechnology, University of Helsinki , Helsinki, Finland.
authors.forename: Andrii
authors.initials: A
authors.lastname: Domanskyi
authors.affiliation: Institute of Biotechnology, University of Helsinki , Helsinki, Finland.
authors.forename: Mart
authors.initials: M
authors.lastname: Saarma
authors.affiliation: Institute of Biotechnology, University of Helsinki , Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Airavaara
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D059290:Dopaminergic Neurons / Q000502:physiology; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000473:pathology / Q000628:therapy*
chemical_list: D009414:Nerve Growth Factors