Pharmacotherapy of idiopathic generalized epilepsies

Background: Idiopathic generalized epilepsies (IGE) represent about 20% of all epilepsies, are genetically determined and comprise several subgroups of syndromes. Although complete seizure control is achievable in about 80% of patients with IGE syndromes, a substantial group remains with inadequate control and unsatisfactory long-term outcome. Several new antiepileptic drugs (AEDs) have been studied in children with IGE. Objectives and Methods: To review the rational drug choice for these patients, the PubMed database was searched with the keywords IGE and AEDs. Results: Older AEDs continue to play a major role in the treatment of IGE. Although the first line monotherapy is still with sodium valproate, new drugs like lamotrigine, levetiracetam and topiramate, are increasingly used in the treatment of IGE. Conclusions: Further research on evidence-based treatment of IGE with new AEDs is needed. New data from molecular genetics of IGE might have the potential to help clinicians choose the most appropriate antiepileptic therapy.     

Overview of new antiobesity drugs

A short overview of new drugs approved for the treatment of obesity (lorcaserin, phentermine/topiramate combination) as well as those with a perspective for approval as antiobesity drugs (cetilistat, naltrexone/bupropion combination, liraglutide) is presented. All these drugs produce significant weight loss accompanied by reductions in cardiometabolic health risks. Although the adverse events were rather rare and tended to decrease with the duration of treatment with most of these medications, the drug-specific safety concerns should be seriously considered. In order to ensure an appropriate, efficient and safe implementation of novel antiobesity drugs into the comprehensive treatment of obesity, it will be necessary to establish a network of physicians and other health-care providers well educated in obesity management.     

The interplay between radiation and the immune system in the field of post-radical pneumonitis and fibrosis and why it is important to understand it

A discussion on the importance and pathogenesis of radiation-induced pneumonitis and fibrosis is provided, with a special focus on the role of the immune system. The need to understand this interaction is highlighted in view of emerging therapeutic potential.     

Efficacy of S-1 in non-small cell lung cancer

Introduction: S-1 is an oral fluoropyrimidine derivative, including three pharmacological compounds: tegafur, gimeracil and oteracil, in a molar ratio of 1: 0.4: 1.

Areas covered: This review addresses the clinical evidence of S-1 in NSCLC in various clinical settings. Currently, S-1 for NSCLC is approved only in Japan. Prospective studies of S-1 as front-line and second-line chemotherapy with or without other agents and concurrent chemoradiotherapy are mainly reviewed. Only two Phase III clinical trials were published or presented for advanced NSCLC. S-1 and cisplatin is an active first-line chemotherapy regimen for advanced NSCLC and S-1 and carboplatin is noninferior to a carboplatin and paclitaexel regimen. The combination of S-1 and a platinum agent is active against NSCLC, regardless of tumor histology.

Expert opinion: It is becoming possible to design effective regimens with S-1 against NSCLC in various clinical settings considering the ethnic differences in pharmacokinetics and a greater understanding of the underlying molecular pathways or biomarkers of NSCLC. Further Phase III studies with S-1 for both early and advanced NSCLC are warranted worldwide.     

Luseogliflozin for the treatment of type 2 diabetes

Introduction: Sodium glucose cotransporter 2 (SGLT2) inhibitors are expected to provide adequate glycemic control, and be safe and well tolerated, for treating type 2 diabetes mellitus (T2DM). Luseogliflozin is a highly selective SGLT2 inhibitor that was recently approved for marketing and launched in Japan to treat T2DM.

Areas covered: This review summarizes the published data regarding the mechanism of action, clinical efficacy, and safety of luseogliflozin for treating T2DM. Other potential benefits of luseogliflozin, including lowering body weight and blood pressure, beyond its glucose-lowering effects are also discussed.

Expert opinion: Luseogliflozin lowers plasma glucose concentration and body weight, and has beneficial effects on other clinically relevant parameters, including blood pressure and uric acid, in patients with T2DM. Although it had a good safety profile in clinical trials, there may be some safety concerns, including a possible decrease in muscle mass and an increase in ketone bodies. Therefore, careful administration and consideration of its benefit–risk balance are necessary. When using luseogliflozin, it is important to select appropriate patients and to adhere to its guidelines for use. If used correctly, luseogliflozin is expected to be positioned as a new type of oral hypoglycemic drug for treating T2DM.     

New developments in immunosuppressive therapy for heart transplantation

Background: Heart transplantation is a well-established therapeutic option for many patients with end-stage heart disease. A major challenge in heart transplantation today is providing effective immunosuppression to prevent graft rejection while minimizing the many adverse effects of currently available therapies. Objective: To systematically review current immunosuppressive treatment strategies after heart transplantation and to review emerging drugs in various stages of development. Methods: A comprehensive literature review was performed using the online PubMed and Pharmaprojects databases. Results/conclusions: This article gives an overview of the immunosuppressive agents in current use, with a detailed review of emerging drugs with novel therapeutic targets.     

The potential of targeting Ras proteins in lung cancer

The Ras pathway is a major driver in lung adenocarcinoma: over 75% of all cases harbor mutations that activate this pathway. While spectacular clinical successes have been achieved by targeting activated receptor tyrosine kinases in this pathway, little, if any, significant progress has been achieved targeting Ras proteins themselves or cancers driven by oncogenic Ras mutants. New approaches to drug discovery, new insights into Ras function, new ways of attacking undruggable proteins through RNA interference and new ways of harnessing the immune system could change this landscape in the relatively near future.     

MmpL3 a potential new target for development of novel anti-tuberculosis drugs

Introduction: Tuberculosis (TB) is still a leading cause of mortality in the developing world and there is an unmet clinical need for new drugs with novel mechanism of action. Targeting the complex and unique cell wall of TB-causing pathogen Mycobacterium tuberculosis (Mtb) has been a mainstay of TB drug discovery. Though, the composition of the cell wall of Mtb is well understood, little is known about the assembly process of the cell wall such as the transport of mycolic acids across the cell wall.

Areas covered: Recent research demonstrating MmpL3 protein as a transmembrane transporter of mycolic acids is discussed. In addition, MmpL3 has also been implicated in heme transport. Research describing several diverse chemical inhibitors that inhibit MmpL3 is reviewed.

Expert opinion: Evidence so far suggests MmpL3 is a transporter of mycolic acids. It has emerged as a novel therapeutic target for Mtb that is essential and for which several small molecule inhibitors have been identified. Identifying the interacting partners, understanding the substrate specificity and the mechanism of transport by MmpL3 are some of the gaps in knowledge that need to be addressed.