Current Reviews in Clinical and Experimental Pharmacology - Current Issue

This review investigates the efficacy of deutetrabenazine in the management of chorea related to HD. Motor, psychological, and cognitive symptoms characterize HD, a neurodegenerative disease. One prominent movement disorder associated with HD is chorea, which results in uncontrollably jerky movements of the muscles. HD has no known cure; instead, symptom management with a variety of medication options is the main goal. Effective management is essential because chorea has a significant impact on patients' quality of life. Dutetrabenazine is the first deuterated medication to receive approval from the US Food and Drug Administration (FDA) for the therapeutic treatment of chorea in Huntington's disease (HD). Treating chorea associated with HD may benefit from the use of deutetrabenazine. The novel compound deutetrabenazine contains deuterium. It inhibits CYP2D6 metabolism, prolongs the half-lives of active metabolites, and may cause persistent systemic exposure while maintaining significant pharmacological action. Deutetrabenazine decreases the release of monoamines, including dopamine, in the synaptic cleft by inhibiting the VMAT2 vesicular monoamine transporter. For chorea, this mechanism has a therapeutic effect. For the treatment of choreiform movement and tardive dyskinesia in HD, the FDA approved deutetrabenazine in 2017. Here we highlight, Deutetrabenazine as a promising new treatment for Huntington's disease chorea, for patients with chorea, deutetrabenazine offers hope for an enhanced quality of life. To completely understand its effectiveness and potential advantages, additional research is necessary, including direct comparison studies, as a result of the mixed study results.

Pulmonary hypertension (PH) is a severe, progressive disorder characterized by elevated pulmonary arterial pressure, leading to right ventricular failure and increased mortality. Despite advancements in management, the median survival for PH patients remains 5-7 years, with an in-hospital mortality rate of approximately 6%. The core pathological feature of PH is pulmonary vascular remodeling (PVR), a multifactorial process involving endothelial dysfunction, inflammation, and aberrant immune responses. While current therapies target endothelial dysfunction, they fall short of preventing PVR or halting disease progression. Emerging research highlights the potential of immune-inflammatory pathways, oxygen-sensing mechanisms, and gut microbiota modulation as therapeutic targets. Integrating nutritional strategies, probiotics, and fecal microbiota transplantation (FMT) as adjunctive therapies also shows promise. These factors may collectively influence PVR, offering novel insights into therapeutic avenues for PH management in the future.

Fatty liver disease (FLD) is a well-known metabolic disorder associated with hepatic steatosis and tissue lipid accumulation. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent and challenging condition that is linked to obesity, diabetes, and other metabolic disorders. MAFLD, previously called NAFLD or nonalcoholic fatty liver disease, is associated with pathological changes in liver tissue. In recent decades, there has been a growing interest in the potential of metformin, a commonly used medication for type-2 diabetes, to help treat MAFLD. Metformin has shown promising potential in treating MAFLD through its ability to modify ferroptosis, a novel form of programmed cell death. In this critical review, we explain the current knowledge about MAFLD, the potential role of ferroptosis in its pathogenesis, and the mechanisms by which metformin may modulate ferroptosis in the context of MAFLD. Additionally, evidence supporting the usage of metformin in treating MAFLD is explained. Overall, this review explains the potential of metformin as a novel therapeutic approach for MAFLD by targeting ferroptosis and provides valuable insights for future research in this area.

The estimated worldwide number of individuals diagnosed with Parkinson's disease (PD) might exceed 10 million by 2040. However, the underlying evidence for PD is unclear. Recent research in Parkinson's disease has focused on exploring the gut-brain axis. Researchers have proposed that gut microbiota and gut dysbiosis contribute to peripheral inflammatory conditions. The involvement of gut pathogens and dysbiosis in peripheral inflammatory diseases has been hypothesized. In Parkinson's disease, the metabolic effects associated with gut dysbiosis accelerate nerve cell loss and damage. The microbiota-gut-brain axis (MGBA) establishes the relationship between the brain and the gut through the bidirectional vagus nerve. The MGBA promotes digestive system regulation and is responsible for maintaining metabolic homeostasis under regular conditions. Helicobacter pylori, Enterococcus faecalis, and Desulfovibrio are gut bacteria whose relative abundance has been associated with Parkinson's disease etiology and treatment efficacy. Numerous clinical and preclinical studies have substantiated the therapeutic potential of probiotics in treating Parkinson's disease via the gut-brain axis. The technique appears to have benefited from a combination of favorable conditions that led to its success. The present study investigated whether administering the probiotic can be a better therapeutic intervention for PD or not. Although widespread, no medicines exist to halt the neurodegenerative effects of PD. Some probiotics raised brain dopamine levels, slowed or stopped neuronal death, and improved motor function in models of toxin-induced and genetic PD in mice, rats, flies, and induced pluripotent stem cells. Probiotics control gut dysbiosis, thereby preventing neurodegeneration in PD via the gut-brain axis. Probiotics are used to control the principal dangers of oxidative stress and alpha-synuclein (α-synuclein) aggregation. Probiotics, which contain beneficial microorganisms such as Lactobacillus, Blautia, Roseburia, Lachnospiraceae, Prevotellaceae, and Akkermansia, may help alleviate PD symptoms and slow the disease's progression. Numerous probiotic bacteria can treat the neurodegenerative condition. As a result, this review paper focuses on the current understanding of the link between PD and gut microbiota while also providing comprehensive information about the neuroprotective function of probiotics.

The two-way communication between intestinal microbiota and the central nervous system (the microbiota-gut-brain axis) is involved in the regulation of brain function, neurodevelopment, and aging. The microbiota-gut-brain axis dysfunction may be a predisposition factor for Parkinson’s disease (PD), Alzheimer’s disease (AD), Autism spectrum disorder (ASD), and other neurological diseases. However, it is not clear whether gut microbiota dysfunction contributes to neuropsychiatric disorders. Changes in the gut microbiota may modulate or modify the effects of environmental factors on neuropsychiatric disorders. Factors that impact neuropsychiatric disorders also influence the gut microbiota, including diet patterns, exercise, stress and functional gastrointestinal disorders. These factors change microbiome composition and function, along with the metabolism and immune responses that cause neuropsychiatric disorders. In this review, we summarized epidemiological and laboratory evidence for the influence of the gut microbiota, metabolism and environmental factors on neuropsychiatric disorders incidence and outcomes. Furthermore, the role of gut microbiota in the two-way interaction between the gut and the brain was also reviewed, including the vagus nerve, microbial metabolism, and immuno-inflammatory responses. We also considered the therapeutic strategies that target gut microbiota in the treatment of neuropsychiatric disorders, including prebiotics, probiotics, Fecal microbiota transplant (FMT), and antibiotics. Based on these data, possible strategies for microbiota-targeted intervention could improve people’s lives and prevent neuropsychiatric disorders in the future.

Previous genetic studies on the genetic makeup of Arab populations highlight the diversity resulting from the distribution of specific genetic markers among various Arab descendant populations. Different genetic variants classified as clinically significant have been identified, impacting the response to administered drugs. Absorption, distribution, and excretion of drugs throughout the human body are managed through the actions of drug transporters and receptor proteins, which are expressed on the cellular membrane. Drug metabolism involves activating or inactivating various compounds, transforming them into therapeutically active or toxic metabolites. With the rapid advancement of pharmacogenetic testing techniques and increased genetic studies involving Arab populations, insights into genetic polymorphisms have emerged, leading to a better understanding of the diverse phenotypes of drug response associated with genotype variation. Variations in transporters and receptor genes have significantly contributed to generating variant phenotypes that affect individuals' responses to treatments and substrates. This necessitates administering individualized drug doses based on the patient's haplotype, which can be determined through advanced genetic diagnosis. This review summarizes the findings of recent pharmacogenetic studies in the Arab world, emphasizing the benefits of pharmacogenetic research and applications to enhance therapeutic aspects of healthcare and treatment among patients in Arab countries.