ABSTRACT
Symptomatic treatments are available for Parkinson's disease and Alzheimer's disease. An unmet need is cure or disease modification. This review discusses possible reasons for negative clinical study outcomes on disease modification following promising positive findings from experimental research. It scrutinizes current research paradigms for disease modification with antibodies against pathological protein enrichment, such as α-synuclein, amyloid or tau, based on post mortem findings. Instead a more uniform regenerative and reparative therapeutic approach for chronic neurodegenerative disease entities is proposed with stimulation of an endogenously existing repair system, which acts independent of specific disease mechanisms. The repulsive guidance molecule A pathway is involved in the regulation of peripheral and central neuronal restoration. Therapeutic antagonism of repulsive guidance molecule A reverses neurodegeneration according to experimental outcomes in numerous disease models in rodents and monkeys. Antibodies against repulsive guidance molecule A exist. First clinical studies in neurological conditions with an acute onset are under way. Future clinical trials with these antibodies should initially focus on well characterized uniform cohorts of patients. The efficiency of repulsive guidance molecule A antagonism and associated stimulation of neurogenesis should be demonstrated with objective assessment tools to counteract dilution of therapeutic effects by subjectivity and heterogeneity of chronic disease entities. Such a research concept will hopefully enhance clinical test strategies and improve the future therapeutic armamentarium for chronic neurodegeneration.
Subject(s)
Neurodegenerative Diseases/therapy , Chronic Disease , Disease Progression , Humans , Translational Research, BiomedicalABSTRACT
HD 66051 is an eclipsing system with an orbital period of about 4.75 d that exhibits out-of-eclipse variability with the same period. New multicolour photometric observations confirm the longevity of the secondary variations, which we interpret as a signature of surface inhomogeneities on one of the components. Using archival and newly acquired high-resolution spectra, we have performed a detailed abundance analysis. The primary component is a slowly rotating late B-type star (T eff = 12500 ± 200 K; log g = 4.0, v sin i = 27 ± 2 km s-1) with a highly peculiar composition reminiscent of the singular HgMn-related star HD 65949, which seems to be its closest analogue. Some light elements as He, C, Mg, Al are depleted, while Si and P are enhanced. Except for Ni, all the iron-group elements, as well as most of the heavy elements, and in particular the REE elements, are overabundant. The secondary component was estimated to be a slowly rotating A-type star (T eff ~ 8000 K; log g = 4.0, v sin i ~ 18 km s-1). The unique configuration of HD 66051 opens up intriguing possibilities for future research, which might eventually and significantly contribute to the understanding of such diverse phenomena as atmospheric structure, mass transfer, magnetic fields, photometric variability and the origin of chemical anomalies observed in HgMn stars and related objects.
