This exploratory, single-group, open-label study investigated 17 patients with Parkinson's disease (PD) using a pre-post design. Motor and non-motor outcomes were assessed through clinical scales, bio Show more
This exploratory, single-group, open-label study investigated 17 patients with Parkinson's disease (PD) using a pre-post design. Motor and non-motor outcomes were assessed through clinical scales, biochemical and genetic analyses, and machine learning models (Gradient Boosting Machines, Random Forests). After treatment with a neurotrophic peptide mixture, improvements were observed in daily activity (16%), cognition (11%), depression (10% reduction), and reactive anxiety (23% reduction). Biological changes included a 45% increase in platelet δ-granules, higher mitochondrial counts, elevated gene expression (notably BDNF in women, p = 0.046), and modulation of oxidative stress markers (17% reduction in TBARS, 30% increase in GSH). Machine learning identified BDNF and PINK1 expression, along with MOCA and MMSE scores, as key predictors of UPDRS improvement. These findings suggest that neurotrophic peptide therapy may influence clinical, structural, and molecular domains in PD. Larger, controlled trials are warranted to confirm therapeutic potential and clarify associations with cognitive and neurotrophic parameters. Show less
The progress in Alzheimer's disease (AD) treatment suggests a combined therapeutic approach targeting the two lesional processes of AD, which include amyloid plaques made of toxic Aβ species and neuro Show more
The progress in Alzheimer's disease (AD) treatment suggests a combined therapeutic approach targeting the two lesional processes of AD, which include amyloid plaques made of toxic Aβ species and neurofibrillary tangles formed of aggregates of abnormally modified Tau proteins. A pharmacophoric design, novel drug synthesis, and structure-activity relationship enabled the selection of a polyamino biaryl PEL24-199 compound. The pharmacologic activity consists of a non-competitive β-secretase (BACE1) modulatory activity in cells. Curative treatment of the Thy-Tau22 model of Tau pathology restores short-term spatial memory, decreases neurofibrillary degeneration, and alleviates astrogliosis and neuroinflammatory reactions. Modulatory effects of PEL24-199 towards APP catalytic byproducts are described in vitro, but whether PEL24-199 can alleviate the Aβ plaque load and associated inflammatory counterparts in vivo remains to be elucidated. We investigated short- and long-term spatial memory, Aβ plaque load, and inflammatory processes in APP Show less