Nihon yakurigaku zasshi. Folia pharmacologica Japonica
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Nippon Yakurigaku Zasshi · Jan 2019
[The functional role of endogenous APJ agonists; Apelin and Elabela/Toddler in cardiovascular diseases].
Apelin is an endogenous peptide ligand for APJ receptor, which is widely expressed in human body, and exerts various physiological effects such as vasodilation, inotropic effect, water balance, heart development, angiogenesis and energy metabolism. The beneficial effects of Apelin in cardiovascular diseases have been elucidated, and the roles of Apelin in aging-associated diseases are recently implicated. The mechanisms for therapeutic effects of Aplein include an antagonistic action to renin-angiotensin system (RAS) in addition to inotropic and vasodilatory actions. ⋯ We and others have shown that Elabela exerts inotropic and protective effects in the heart. Although the number of heart failure patients is rapidly increasing, the pathophysiology of heart failure remains elusive and further development of new therapeutic option is awaited. Apelin is a unique bifunctional molecule, which has both inotropic and cardioprotective effects in heart failure, and thus further elucidation of the mechanisms for Apelin/Elabela-APJ signaling would contribute to development of a novel therapeutics for heart failure patients.
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Nippon Yakurigaku Zasshi · Jan 2019
Review[Identification of biomarkers and new therapies for taxane-induced peripheral neuropathy].
Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect frequently caused by taxanes. Because the mechanisms underlying CIPN pathogenesis remain to be fully elucidated, there is no indicator for objective diagnosis like a biomarker. In addition, treatment options for CIPN is still unsatisfactory. ⋯ Recently, in a paclitaxel CIPN model mouse, we found that an inflammatory factor is released from dedifferentiated Schwann cells in the mouse sciatic nerve into the blood, highly correlated with the on-set of mechanical hypersensitivity. On the other hand, considering our previous findings, it seems that some drugs, which supply newly formed mature Schwann cells at the sites of demyelinated lesions, may be a new beneficial therapy for taxane-induced peripheral neuropathy. In this review, we will introduce our findings about new therapeutic drug candidate for taxane-related CIPN based on this concept, and plasma biomarker to detect CIPN on-set and progression.
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Nippon Yakurigaku Zasshi · Jan 2018
Randomized Controlled Trial[Pharmacological and clinical profile of spinal muscular atrophy (SMA) therapeutic drug nusinersen (Spinraza®)].
Nusinersen (Spinraza®) was approved as Japan's first antisense oligonucleotide (ASO) drug for treatment of SMA (spinal muscular atrophy) patients with a deletion or mutation of the survival motor neuron (SMN) 1 gene and ≥1 copy of the SMN2 gene. Nuseinersen is a fully modified 2'-O-(2-methoxyethyl) (2'-MOE) ASO designed to bind the SMN2 pre-mRNA and alter splicing, such that a mature mRNA is produced and is translated as full-length SMN protein. In 4 types of mouse SMA disease models, treatment with nusinersen improved the form of the neuromuscular junction, increased myofiber size, improved righting reflex and grip, and prolonged survival. ⋯ Moreover, both studies showed that greater efficacy may be obtained with early initiation of nusinersen treatment. Therefore, treatment with nusinersen should be started as early as possible to delay or halt progression of the disease and maximize therapeutic effect. As nusinersen is the only ASO currently available for SMA, it will be widely used, therefore we will expect that nusinersen will contribute to improve patients' QOL and reduce the burden of caregivers and the healthcare system by improving motor function of patients with SMA.