View Point: Disease Modification and Cell Secretome Based Approaches in Parkinson's Disease: Are We on the Right Track?

Abstract

The term idiopathic Parkinson’s disease describes an entity of various not well-characterized disorders resembling each other. They are characterized by chronic neuronal dying originating from various disease mechanisms. They result in the onset of motor and related non-motor features, both of which respond to administration of personalized drug combinations and surgical therapies. The unmet need is beneficial disease course modification with repair and neurogenesis. Objectives are to discuss the value of cell secretome based treatments including neuronal graft transplantation and to suggest as an alternative the stimulation of an endogenous available approach for neuronal repair. Chronic neurodegenerative processes result from different heterogeneous, but complementing metabolic, pathological cascade sequences. Accumulated evidence from experimental research suggested neuron transplantation, stem cell application and cell secretome-based therapies as a promising future treatment with cure as an ultimate goal. To date, clinical testing of disease-modifying treatments has focused on substitution or repair of the remaining dopamine synthesizing neurons following diagnosis. At diagnosis, many of the still surviving and functioning, but already affected neurons have lost most of their axons and are primed for cell death. A more promising therapeutic concept may be the stimulation of an existing, endogenous repair system in the peripheral and central nervous systems. The abundant protein repulsive guidance molecule A blocks restoration and neurogenesis, both of which are mediated via the neogenin receptor. Inhibition of the physiological effects of repulsive guidance molecule A is an endogenous available repair pathway in chronic neurodegeneration. Antagonism of this protein with antibodies or stimulation of the neogenin receptor should be considered as an initial repair step. It is an alternative to cell replacement, stem cell or associated cell secretome concepts.