An ever-expanding number of frontiers of novel and revolutionary treatments is being explored by scientists in their efforts to combat Parkinson’s disease (PD).
A new trial, outcomes of which were published this month in Brain, tested the clinical efficacy of delivering a neurotrophic factor called GDNF directly into the brain area affected by the disease. When glial cell-derived neurotrophic factor (GDNF) was first identified along with the other factors, it was trialled in animal models of the disease and showed promising results. For instance, in rodent models of PD, which use a toxin that specifically targets dopaminergic cells that are lost in the course of disease, supplying GDNF factor was found to preserve those neurons previously exposed to the toxin. Neurotrophic factors essentially act to block any programmed cell death of neutrons and increase the number of signalling molecules that allow the cell to survive and proliferate. Their sole function seemed to be the much-anticipated key to reversing neuronal cell death and loss in PD.
Unfortunately, the subsequent randomised, double-blinded trial assessing the efficacy of administering GDNF directly into putamen did not find any statistically significant differences between treatment and placebo groups. Both groups showed a decrease in motor symptoms, potentially owing to the effect of placebo in such clinical trials, hindering clear understanding of the effects of the agent in question. However, almost half of all patients who had GDNF administered (compared to none from the placebo group) had a large decrease in their motor symptom score. Moreover, it was found through positron-emission tomography (PET) scanning that dopamine precursor uptake was significantly greater in the GDNF-treated patient group, indicating that dopaminergic cells in those patients are synthesising dopamine in higher amounts and hence are more actively functioning compared to the placebo-treated group. This indicates that this treatment and treatment with other neurotrophic factors, if administered using the same revolutionary delivery method, still hold promise if tested again in a wider setting of patients. The failure of this trial in part, in my opinion, could be explained by the relatively long duration of the disease (over 5 years since motor symptom onset). If this disease duration is decreased in subsequent trials, better results might be expected, as a greater number of neurons is lost the longer it has been since diagnosis. Therefore, if the factor is given at the earlier stages of the disorder, it may prevent the irreversible loss of vulnerable neurons that drive the progression of the disease.