[Cell therapy and other neuroregenerative strategies in Parkinson's disease (II)].
OBJECTIVE
To review, from a mainly clinical standpoint, the different strategies applied to regenerate or restore the nigrostriatal dopaminergic system in Parkinson's disease (PD). A previous first part focused on the results of adrenal medulla and human fetal mesencephalic transplants, and this second part addresses transplants of other cell types, administration of trophic factors, and gene therapy.


METHODS
As an alternative to human fetal mesencephalic neurons, other donor cells types (porcine mesencephalic neurons, retinal pigment epithelial cells) with similar 'dopaminergic' action mechanism have been tried, although with heterogeneous results. Transplantation of carotid body cell aggregates may be a promising therapy because of its neurotrophic action mechanism. The perspectives of cell therapies based on genetically modified cells and precursor cells of different origin are also reviewed. Among other neuroregenerative approaches, the clinical outcomes of direct administration of neurotrophic factors and the perspectives for in vivo gene therapy are also addressed.


CONCLUSIONS
The objective of neuroregenerative therapy for PD should include trophic restoration of damaged neuronal systems, since improvement in striatal dopaminergic function is not sufficient. After the recent failure of the direct (intraventricular or intraputaminal) administration of glial cell line-derived neurotrophic factor (GDNF), attention of researchers has focused on indirect methods, including transplantation of GDNF-producing cells (carotid body cell aggregates or different genetically modified cells), and in vivo gene therapy.
Mínguez-Castellanos
A
A
Servicio de Neurología, Hospital Universitario Virgen de las Nieves, Granada, Spain. aminguezc@meditex.es
Escamilla-Sevilla
F
F
D016380:Brain Tissue Transplantation; D064987:Cell- and Tissue-Based Therapy; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D009414:Nerve Growth Factors / Q000627:therapeutic use; D009416:Nerve Regeneration / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010300:Parkinson Disease / Q000628:therapy*
D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D004298:Dopamine