Using Stem Cell and Gene Therapy Technologies to Treat Parkinson's Disease

A recent study led by Aponso and colleagues provides first quantitative evidence for an alteration in the production of endogenous cell proliferation in the SVZ, SN and midbrain (with a failure of neurogenesis) as a result of a partial progressive 6-OHDA lesion (36). Results are suggestive of endogenous neural progenitor cells in the striatum and the SN can provide potential repair for PD, but require alteration or modulation of environmental cues to suppress astrogenesis in the striatum and enhance or direct neurogenesis or DAergic differentiation to replace the degenerating neurons in the SN (36). However, despite the establishment that proliferation takes place (33), the appropriate and adequate Migration, Differentiation and integration of DA neurons is essential for a consequent change and improvement in motor phenotype.  Indeed, autologous transplantation of adult neural stem cells has been attempted clinically in at least one patient with PD, with mixed results (37).

Conclusion

The stagnant success of pharmacotherapy and surgical methods in treating PD has instigated the search for novel treatment options, two of which are discussed here. Gene therapy is a relatively new field. Apart from increasing DA, it has been used to deliver anti-apoptotic agents, grown factors and recessive genes in an attempt to provide neurorestoration and neuroprotection. There exist 3 clinical trials for PD date, all of which have seen some success in impeding PD and achieving behavioural motor improvements in patients.   Novel cell replacement strategies transplant DA into the depleted ST. Knowledge about the integration of DAergic neurons, more specifically the synaptic and neurotrophic mechanisms controlling their involvement in the basal ganglia circuitry is essential for clear relevance in human trials.  Stem cell technology however has gained more focus recently, with ESC and NSC being used. The stimulation of endogenous neural stem cells in particular holds great potential. Novel strategies thus hold great potential for the modification of the natural course of PD, particularly with respect to protecting healthy cells and preventing loss of persisting ones.

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