👤 Ramón Cacabelos

Atremorine is a novel bioproduct obtained by nondenaturing biotechnological processes from a genetic species of Vicia faba. Atremorine is a potent dopamine (DA) enhancer with powerful effects on the neuronal dopaminergic system, acting as a neuroprotective agent in Parkinson's disease (PD). Over 97% of PD patients respond to a single dose of Atremorine (5 g, p.o.) 1 h after administration. This response is gender-, time-, dose-, and genotype-dependent, with optimal doses ranging from 5 to 20 g/day, depending upon disease severity and concomitant medication. Drug-free patients show an increase in DA levels from 12.14 ± 0.34 pg/ml to 6463.21 ± 1306.90 pg/ml; and patients chronically treated with anti-PD drugs show an increase in DA levels from 1321.53 ± 389.94 pg/ml to 16,028.54 ± 4783.98 pg/ml, indicating that Atremorine potentiates the dopaminergic effects of conventional anti-PD drugs. Atremorine also influences the levels of other neurotransmitters (adrenaline, noradrenaline) and hormones which are regulated by DA (e.g., prolactin, PRL), with no effect on serotonin or histamine. The variability in Atremorine-induced DA response is highly attributable to pharmacogenetic factors. Polymorphic variants in pathogenic (SNCA, NUCKS1, ITGA8, GPNMB, GCH1, BCKDK, APOE, LRRK2, ACMSD), mechanistic (DRD2), metabolic (CYP2D6, CYP2C9, CYP2C19, CYP3A4/5, NAT2), transporter (ABCB1, SLC6A2, SLC6A3, SLC6A4) and pleiotropic genes (APOE) influence the DA response to Atremorine and its psychomotor and brain effects. Atremorine enhances DNA methylation and displays epigenetic activity via modulation of the pharmacoepigenetic network. Atremorine is a novel neuroprotective agent for dopaminergic neurons with potential prophylactic and therapeutic activity in PD. Show less

Alzheimer's disease (AD) is a polygenic/complex disorder in which genomic, epigenomic, cerebrovascular, metabolic, and environmental factors converge to define a progressive neurodegenerative phenotype. Pharmacogenetics is a major determinant of therapeutic outcome in AD. Different categories of genes are potentially involved in the pharmacogenetic network responsible for drug efficacy and safety, including pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes. However, most drugs exert pleiotropic effects that are promiscuously regulated for different gene products. Only 20% of the Caucasian population are extensive metabolizers for tetragenic haplotypes integrating Show less

The study of variations in genes involved in the different events that trigger the atherogenic process, such as lipid metabolism (modification of LDL-cholesterol), endothelial function and hypertension, immune response (recruitment of macrophages and foam cell formation) and stability of atherosclerotic plaques (thrombosis), established the risk for suffering a vascular disorder. A total of 2455 cases over 50 years of age were genotyped for a panel of 19 SNPs in 15 genes encoding for proteins involved in the atherogenic process. This study shows the relevance of polymorphisms in APOB (odds ratio (OR), 1.17; 95% confidence interval (95% CI), 0.74-1.85), APOC3 (OR, 1.33; 95% CI, 0.82-2.17) and APOE (OR, 1.75; 95% CI, 1.09-2.80), as genetic risk markers for hypercholesterolemia; polymorphisms in ACE (OR, 1.68; 95% CI, 0.32-8.77) and AGT (OR, 1.74; 95% CI, 0.97-3.14) for hypertension; and in APOE*3/*4 (OR, 2.06; 95% CI, 1.70-2.51) and APOE*4/*4 (OR, 3.08; 95% CI, 1.85-5.12) as unambiguous markers of dementia. Our results also showed the transversal importance of proinflammatory cytokines in different stages of atherogenesis, with special relevance of IL6 (OR, 1.39; 95% CI, 0.56-3.49) and TNF (OR, 1.40; 95% CI, 0.92-2.15) related to hypercholesterolemia and hypertension. The set of markers involved in this genetic risk panel makes it a powerful tool in the management of patients with different vascular disorders. Show less