Parkinson's disease and growth factors - are they the answer?

The core loss of dopaminergic neurons in the substantia nigra in Parkinson's disease (PD) coupled to the therapeutic benefits of dopaminergic therapies in patients, simplifies the treatment strategy for this disease. In the context of neurotrophic factors, this distils down to the simple question as to whether a factor exists for these cells that can promote their survival in the face of the degenerative disease process. If such a factor exists, and GDNF seems a strong candidate, then one could anticipate that this treatment would be as effective as L-dopa therapy. However it would not be better than this, nor curative, given the extensive pathology in PD. To date a number of clinical trials have been undertaken in which GDNF has been directly delivered to the PD brain. In addition there have been studies in which neurturin (part of the GDNF family) has also been delivered to the CNS using a viral vector delivery system. These trials have produced mixed results. Importantly though, some patients have shown a sustained clinical response to this treatment which correlates with evidence of increased dopaminergic activity in the brain at the site of delivery using F-dopa PET as well as in a single post-mortem study. The challenge therefore is not whether this approach works, because it self-evidently does in some patients, but rather how we can do this more consistently.