The Complex Cascade of Parkinson’s Disease: Sniffing out a Therapy?

Roger J. Bick, Marie-Francoise Doursout, Brian J. Poindexter

Departments of Pathology and Anesthesiology, McGovern Medical School, UT Health, University of Texas Health Science Center at Houston, TX, USA

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A suitable therapy for combating Parkinson’s disease (PD) neurodegeneration has not been forthcoming and although treatments are available to slow progression, there is no cure and no medical repair procedures.

Of great interest to neurologists and neurology researchers have been the new findings with neurotrophic factors such as glial-cell derived neurotrophic factor and brain-derived neurotrophic factor, the neurotrophins being shown to have the ability to slow neurodegeneration and, in certain instances, rescue neurons. Unfortunately, outcomes of treatments using these proteins have been disappointing or inconclusive at best, and this includes direct infusion into areas of the brain. There is a consensus that once this disease starts there is little chance of halting its progress.

One of the first indications that PD is a future possibility in a patient is a loss of olfaction. We have taken this as a starting point, maybe the earliest indication that neurotrophin treatment should be initiated with the possibility that if this isn’t a cure, it is a potent retardant of inevitable neuron loss and attenuating at least some of the many associated problems. Our work showed in cell cultures and an endotoxin animal model that synthesis of GDNF lagged behind inflammatory cell invasion, release of cytokines, protein folding problems and microglial activation.

Our hypothesis is, that early interventions with neurotrophins might delay devastating neuronal loss and overcome some of the inflammatory effects, and that this treatment could begin at the time of loss of olfaction, together with prescribing anti-inflammatories. Couple this with blocking nitric oxide synthase increases and a reasonably early starting point for treatment might well be found. Journal of Nature and Science (JNSCI), 2(11):e249, 2016

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