- |||||||||| Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Preclinical, Journal: Inhibition of RhoA and mTORC2/Rictor by Fingolimod (FTY720) induces p21-activated kinase 1, PAK-1 and amplifies podosomes in mouse peritoneal macrophages. (Pubmed Central) - Jun 28, 2019 The activity of RhoA and Rac 1 is in turn regulated by mTOR/mTORC2 pathway. Here we showed that a fungus metabolite Fingolimod (FTY720, Gilenya), which is clinically approved for the treatment of multiple sclerosis, down-regulates Rictor, which is a signature molecule of mTORC2 and dictates its substrate (actin cytoskeleton) specificity, down-regulates RhoA, up-regulates PAK-1, and causes amplification of podosomes in mouse peritoneal macrophages.
- |||||||||| FTY720, Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe, selisistat (SEN-196) / AOP Orphan Pharma
Journal: Propofol attenuates high glucose-induced P66shc expression in human umbilical vein endothelial cells through Sirt1. (Pubmed Central) - Jun 26, 2019 Our results suggested that propofol inhibited high glucose-induced p66shc expression via upregulation of sirt1 expression in hyperglycemic HUVECs. Moreover, propofol protects against high glucose-mediated ROS accumulation and endothelial injury via both inhibition of p66shc expression and dephosphorylation of Ser36-p66shc.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Biomarker, Journal: Neurology (Pubmed Central) - Jun 26, 2019 The use of levodopa-carbidopa intestinal gel and a subcutaneous apomorphine infusion allow a reduction of motor fluctuations in Parkinson's disease. Eculizumab appears as an alternative treatment in severe forms of myasthenia gravis.
- |||||||||| FTY720, Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
P2 data, Journal: Blood neurofilament light as a potential endpoint in Phase 2 studies in MS. (Pubmed Central) - Jun 21, 2019 Assuming a 20-40% treatment-related reduction in NfL levels, 143-28 patients per arm will be required. Blood NfL may qualify as an informative and easy-to-measure endpoint for future Phase 2 clinical studies that captures both inflammatory- and noninflammatory-driven neuroaxonal injury in RRMS.
- |||||||||| Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Journal: Acute Fingolimod Effects on Baroreflex and Cardiovascular Autonomic Control in Multiple Sclerosis. (Pubmed Central) - Jun 18, 2019 Our findings indicate that although the first dose of fingolimod invariably activates the parasympathetic system, in several subjects, it may induce also a surge in the sympathetic cardiac drive. This suggests that not only the vagal, as usually assumed, but also the sympathetic autonomic branch should be considered in the risk profile assessment of MS patients starting treatment with fingolimod.
- |||||||||| FTY720, Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Review, Journal: Emerging evidence for the modulation of exocytosis by signalling lipids. (Pubmed Central) - Jun 15, 2019 In the present Review, we discuss recent investigations suggesting that endogenous signalling lipids and synthetic analogues can modulate important physiological aspects of secretion, such as quantal release, vesicle recruitment into active sites, vesicle transport and even organelle fusion in the cytosol. Therefore, these compounds are far from being merely structural components of cellular membranes.
- |||||||||| FTY720, Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Review, Journal: An update on sphingosine-1-phosphate receptor 1 modulators. (Pubmed Central) - Jun 15, 2019 In pursuit of improved stability, bioavailability, and efficiency, structural analogues of this initial prodrug have emerged over time. This review covers a brief introduction to the sphingolipid metabolism, the mechanism of action on S1P, and an updated overview of synthetic sphingosine S1P agonists.
- |||||||||| FTY720, Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Biomarker, Journal: Acid sphingomyelinase: No potential as a biomarker for multiple sclerosis. (Pubmed Central) - Jun 15, 2019 Although higher levels in MS patients were found, ASM activity levels do not show potential as a biomarker for predicting disease activity, progression or response to DMT. Two ceramides and four types of sphingomyelin require further investigation as potential markers for treatment response.
- |||||||||| Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Journal: FTY720 controls disease severity and attenuates sciatic nerve damage in chronic experimental autoimmune neuritis. (Pubmed Central) - Jun 15, 2019 We have shown that FTY720 is an effective immunomodulatory agent, improving the disease course of c-EAN, preserving the myelinated fibers, attenuating the axonal degeneration, and decreasing the number of infiltrated inflammatory cells in peripheral nerves. These data confirm the interest of testing FTY720 or molecules targeting S1P in human peripheral neuropathies.
- |||||||||| FTY720, Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Review, Journal: The Pak1 signalling pathway in cardiac disease: from mechanistic study to therapeutic exploration. (Pubmed Central) - Jun 9, 2019 This review also discusses the anti-arrhythmic and anti-hypertrophic protective role of Pak1 and beneficial effects of FTY-720 (Fingolimod, FDA approved sphingolipid drug), a Pak1 activator in the prevention of arrhythmias and cardiac hypertrophy. These findings shed light on the therapeutic potential of Pak1 signalling in the treatment and prevention of cardiac diseases.
- |||||||||| FTY720, Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Journal: T-Cell Accumulation in the Hypertensive Brain: A Role for Sphingosine-1-Phosphate-Mediated Chemotaxis. (Pubmed Central) - Jun 6, 2019 Inhibition of S1P₁-guided T-cell chemotaxis with the S1P receptor modulator FTY720 protects from augmentation of brain CD3 expression and the development of memory deficits in hypertensive WT mice. In conclusion, our data highlight a new approach to the understanding of hypertension-associated inflammation in degenerative processes of the brain during disease progression.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics, Mayzent (siponimod) / Novartis, Sunosi (solriamfetol) / Jazz
Journal: Pharmaceutical Approval Update. (Pubmed Central) - Jun 6, 2019 In conclusion, our data highlight a new approach to the understanding of hypertension-associated inflammation in degenerative processes of the brain during disease progression. Sunosi (solriamfetol) tablets for excessive daytime sleepiness with narcolepsy or obstructive sleep apnea; Zulresso (brexanolone) injection for postpartum depression in adults; Mayzent (siponimod) tablets for adults with relapsing forms of MS.
- |||||||||| Zeposia (ozanimod) / BMS, avadomide (CC-122) / BMS
Trial completion, Trial completion date, Trial primary completion date: Drug-drug Interaction Study of Ozanimod With Inhibitor or Inducer of CYP2C8 and/or CYP3A (clinicaltrials.gov) - May 30, 2019 P1, N=100, Completed, Recruiting --> Completed | Trial completion date: Feb 2019 --> Sep 2018 Recruiting --> Completed | Trial completion date: Apr 2019 --> Aug 2018 | Trial primary completion date: Jan 2019 --> Aug 2018
- |||||||||| fingolimod / Generic mfg.
Enrollment open: Fingolimod in Treating Patients With Chemotherapy-Induced Neuropathy (clinicaltrials.gov) - May 29, 2019 P1, N=10, Recruiting, Recruiting --> Completed | Trial completion date: Apr 2019 --> Aug 2018 | Trial primary completion date: Jan 2019 --> Aug 2018 Not yet recruiting --> Recruiting
- |||||||||| Gilenya (fingolimod) / Novartis, Mitsubishi Tanabe
Clinical, Journal: Effect of fingolimod on white blood cell, lymphocyte and neutrophil counts in MS patients. (Pubmed Central) - May 28, 2019 While fingolimod has been effectively proven as reducing lymphocyte cells in most patient populations, its effects on neutrophils have not been studied in abundance. Also, there may be sex-related differences in responses to fingolimod treatment with regards to lymphocytes and neutrophils, suggesting a possible difference in RRMS pathogenesis between males and females.
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