Monoclonal antibodies blocking CGRP for prevention of migraine

Introduction and purpose Monoclonal antibodies blocking calcitonin gene-related peptide (CGRP) are a novel treatment strategy developed specifically for prevention of migraine. Four drugs belong to this group: eptinezumab, fremanezumab and galcanezumab, which bind to the peptide; and erenumab, which blocks the CGRP receptor. CGRP is involved in nociception and plays a crucial role in the pathophysiology of migraine, as it is released in the trigeminal ganglion as a response to local cerebral vasoconstriction in order to cause dilation of the vessels and maintain cerebral blood flow. Moreover, administration of CGRP, especially among migraineurs, induces a migraine-type headache. The aim of the paper is to discuss the potential of monoclonal antibodies blocking CGRP for the prevention of migraine and to outline their safety and efficacy profile. State of knowledge Several randomised clinical trials have shown a significant efficacy of these drugs compared to placebo in reducing monthly migraine affected days, among patients suffering from both episodic and chronic migraine. Incidence rate of side effects is low; the most common were mild to moderate (e.g. pain at the injection site, upper respiratory tract infections, nasopharyngitis, back pain and urinary tract infection). Anti-CGRP monoclonal antibodies exhibit a superior benefit-to-risk ratio than established preventive treatments. Conclusions Randomized controlled trials are still needed in order to compare different anti-CGRP monoclonal antibodies and asses their long-term safety profile. In conclusion, these drugs seem to provide promising prospects of improving the lives of migraineurs. As based on current knowledge, the benefits are superior to the likelihood of harm

Gilbert’s syndrome as a protection against the development of other diseases

Introduction and purpose Gilbert's syndrome is a condition caused by a mutation in the gene responsible for the enzyme UDP-glucuronosyltransferase 1A1, which conjugates bilirubin in hepatocytes. Its less efficient functioning results in disorder of bilirubin metabolism which leads to increased level of this compound. It has been observed that there is interesting correlation between elevated levels of bilirubin and the risk of developing certain diseases in patients with this condition. The aim of this review is to understand the correlation between elevated bilirubin levels and the risk of developing selected diseases in individuals with Gilbert's syndrome and how to use this knowledge in innovative therapeutic options.  State of knowledge Bilirubin was considered a non-functional waste product of heme breakdown, used to be seen as a concerning indicator of liver disease or even a potentially harmful substance for the nervous system. However, lately it turns out that bilirubin has strong antioxidant properties, which help to scavenge free radicals and inhibit lipid oxidation. Recent studies have shown that even slightly elevated levels of bilirubin in the blood, such as those commonly found in individuals with Gilbert's syndrome may protect these patients against diseases associated with increased oxidative stress, an overactive immune response and metabolic dysfunction.  Conclusions As a result, individuals with Gilbert's syndrome are observed to have a lower risk of developing diseases related to oxidative stress, such as cardiovascular diseases and cancer. In these patients mortality rate compared to the population with normobilirubinemia is decreased. Based on available studies, it has also been concluded that inducing mild hyperbilirubinemia - iatrogenic Gilbert's syndrome - using appropriate substances may have health benefits.&nbsp