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Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics

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https://www.readbyqxmd.com/read/28812229/economics-and-cost-effectiveness-of-multiple-sclerosis-therapies-in-the-usa
#1
REVIEW
Daniel M Hartung
Multiple sclerosis (MS) is a disabling, chronic disease that imposes a significant economic burden on patients and the US healthcare system. The largest cost component for individuals with MS are prescription drugs, specifically disease-modifying therapies (DMTs). Despite an increase in the number and diversity of DMTs over the past 10 years, acquisition costs for all DMTs have escalated dramatically at rates substantially higher than medical inflation. Currently, costs for most DMTs exceed $70,000 a year. Recent cost-effectiveness studies suggest the cost for nearly all DMTs exceeds generally accepted thresholds for what is considered a good value in the USA, even after factoring expected rebates...
August 15, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28812220/sphingosine-1-phosphate-receptor-modulators-for-the-treatment-of-multiple-sclerosis
#2
REVIEW
Burhan Z Chaudhry, Jeffrey A Cohen, Devon S Conway
Sphingosine 1-phosphate receptor (S1PR) modulators possess a unique mechanism of action in the treatment of multiple sclerosis (MS). Subtype 1 of the S1PR is expressed on the surface of lymphocytes and is important in regulating egression from lymph nodes. The S1PR modulators indirectly antagonize the receptor's function leading to sequestration of lymphocytes in the lymph nodes. Fingolimod was the first S1PR modulator to receive regulatory approval for relapsing-remitting MS after 2 phase III trials demonstrated potent efficacy, safety, and tolerability...
August 15, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28785958/wellness-and-the-role-of-comorbidities-in-multiple-sclerosis
#3
REVIEW
Brandon P Moss, Mary R Rensel, Carrie M Hersh
Multiple sclerosis (MS) is a demyelinating and neurodegenerative disorder of the central nervous system, for which disease modifying therapies (DMTs) are the mainstay treatment approach to reduce inflammatory disease activity and slow worsening disability. In addition to conventional pharmacologic therapy, there is growing interest in the use of lifestyle strategies to support wellness and mitigate disease-related complications in MS. This interest stems from a growing appreciation of the role of certain comorbidities and lifestyle factors on disease activity, disability, mortality, and overall quality of life...
August 7, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28779373/ethical-considerations-of-patient-funded-research-for-multiple-sclerosis-therapeutics
#4
REVIEW
Lilyana Amezcua, Flavia Nelson
Patient-funded research has started to emerge in multiple sclerosis studies, such as low-dose naltrexone and stem-cell therapy. While these represent greater opportunities for the physician, scientist, and patient, ethical concerns concerning protocol review, conflict of interests, and protection of subjects are reviewed.
August 4, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28770481/the-role-of-advanced-magnetic-resonance-imaging-techniques-in-multiple-sclerosis-clinical-trials
#5
REVIEW
Kedar R Mahajan, Daniel Ontaneda
Magnetic resonance imaging has been crucial in the development of anti-inflammatory disease-modifying treatments. The current landscape of multiple sclerosis clinical trials is currently expanding to include testing not only of anti-inflammatory agents, but also neuroprotective, remyelinating, neuromodulating, and restorative therapies. This is especially true of therapies targeting progressive forms of the disease where neurodegeneration is a prominent feature. Imaging techniques of the brain and spinal cord have rapidly evolved in the last decade to permit in vivo characterization of tissue microstructural changes, connectivity, metabolic changes, neuronal loss, glial activity, and demyelination...
August 2, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28766273/pregnancy-effect-on-multiple-sclerosis-treatment-considerations-and-breastfeeding
#6
REVIEW
Rhonda Voskuhl, Callene Momtazee
Multiple sclerosis (MS) commonly affects women in childbearing years making pregnancy issues important for patients with MS and their families. Pregnancy is a naturally occurring disease modifier of MS associated with a 70% reduction in relapse rates in the third trimester. This relapse rate reduction during the last trimester is roughly equal to the most effective disease-modifying treatments for MS. Given this efficacy, various pregnancy factors have been tested to determine which play a part in pregnancy's protection, and some have been translated to completed and ongoing phase II clinical trials...
August 1, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28744714/erratum-to-chronic-paroxetine-treatment-prevents-the-emergence-of-abnormal-electroencephalogram-oscillations-in-huntington-s-disease-mice
#7
Sandor Kantor, Janos Varga, Shreya Kulkarni, A Jennifer Morton
No abstract text is available yet for this article.
July 25, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28707278/daclizumab-development-clinical-trials-and-practical-aspects-of-use-in-multiple-sclerosis
#8
REVIEW
Laura E Baldassari, John W Rose
Daclizumab is a humanized monoclonal antibody directed towards CD25, the alpha subunit of the high-affinity interleukin (IL)-2 receptor. Daclizumab exerts its effects via multiple mechanisms, including reduction of IL-2-mediated lymphocyte activation and upregulation of CD56-bright natural killer cells. Intravenous daclizumab (Zenapax™) was initially approved for prevention of rejection in renal transplant. In subsequent early testing, followed by larger-scale phase II and phase III trials, both intravenous and subcutaneous daclizumab have demonstrated clinical efficacy in the treatment of multiple sclerosis...
July 13, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28707277/open-label-allopregnanolone-treatment-of-men-with-fragile-x-associated-tremor-ataxia-syndrome
#9
J Y Wang, A M Trivedi, N R Carrillo, J Yang, A Schneider, C Giulivi, P Adams, F Tassone, K Kim, S M Rivera, N Lubarr, C-Y Wu, R W Irwin, R D Brinton, J M Olichney, M A Rogawski, R J Hagerman
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting approximately 45% of male and 16% of female carriers of the FMR1 premutation over the age of 50 years. Currently, no effective treatment is available. We performed an open-label intervention study to assess whether allopregnanolone, a neurosteroid promoting regeneration and repair, can improve clinical symptoms, brain activity, and magnetic resonance imaging (MRI) measurements in patients with FXTAS. Six patients underwent weekly intravenous infusions of allopregnanolone (2-6 mg over 30 min) for 12 weeks...
July 13, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28695472/assessing-repair-in-multiple-sclerosis-outcomes-for-phase-ii-clinical-trials
#10
REVIEW
Maria Pia Sormani, Matteo Pardini
Multiple Sclerosis (MS) pathology is complex and includes inflammatory processes, neurodegeneration, and demyelination. While multiple drugs have been developed to tackle MS-related inflammation, to date there is scant evidence regarding which therapeutic approach, if any, could be used to reverse demyelination, foster tissue repair, and thus positively impact on chronic disability. Here, we reviewed the current structural and functional markers (magnetic resonance imaging, positron emission tomography, optical coherence tomography, and visual evoked potentials) which could be used in phase II clinical trials of new compounds aimed to foster tissue repair in MS...
July 10, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28695471/ocrelizumab-and-other-cd20-b-cell-depleting-therapies-in-multiple-sclerosis
#11
REVIEW
Jeffrey M Gelfand, Bruce A C Cree, Stephen L Hauser
Selective depletion of CD20(+) B cells by anti-CD20 monoclonal antibodies as monotherapy in multiple sclerosis (MS) profoundly suppresses acute inflammatory disease activity and signifies an important advance in the treatment of relapsing-remitting MS. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, is also the first proven therapy to lessen disability progression in primary progressive MS-a breakthrough for patients with a disease that had no proven therapy. Ocrelizumab is generally well tolerated, with the most common adverse events experienced being infusion reactions and infections...
July 10, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28653282/therapeutic-targets-for-multiple-sclerosis-current-treatment-goals-and-future-directions
#12
REVIEW
Andrew L Smith, Jeffrey A Cohen, Le H Hua
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, and the most common cause of nontraumatic disability in young adults. Most patients have a relapsing-remitting course, and roughly half of them will eventually enter a degenerative progressive phase, marked by gradual accrual of disability over time in the absence of relapses. Early initiation of treatment has delayed the onset of disability progression. Thus, there is increased interest in treating to target in MS, particularly targeting no evidence of disease activity...
June 26, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28653281/fingolimod-exerts-only-temporary-antiepileptogenic-effects-but-longer-lasting-positive-effects-on-behavior-in-the-wag-rij-rat-absence-epilepsy-model
#13
Antonio Leo, Rita Citraro, Nicola Amodio, Caterina De Sarro, Maria Eugenia Gallo Cantafio, Andrew Constanti, Giovambattista De Sarro, Emilio Russo
One of the major challenges in the epilepsy field is identifying disease-modifying drugs in order to prevent or delay spontaneous recurrent seizure onset or to cure already established epilepsy. It has been recently reported that fingolimod, currently approved for the treatment of relapsing-remitting multiple sclerosis, has demonstrated antiepileptogenic effects in 2 different preclinical models of acquired epilepsy. However, to date, no data exist regarding the role of fingolimod against genetic epilepsy. Therefore, we have addressed this issue by studying the effects of fingolimod in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, a well-established genetic model of absence epilepsy, epileptogenesis, and neuropsychiatric comorbidity...
June 26, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28653279/chronic-paroxetine-treatment-prevents-the-emergence-of-abnormal-electroencephalogram-oscillations-in-huntington-s-disease-mice
#14
Sandor Kantor, Janos Varga, Shreya Kulkarni, A Jennifer Morton
Disturbance of rapid eye movement (REM) sleep appears early in both patients with Huntington's disease (HD) and mouse models of HD. Selective serotonin reuptake inhibitors are widely prescribed for patients with HD, and are also known to suppress REM sleep in healthy subjects. To test whether selective serotonin reuptake inhibitors can correct abnormal REM sleep and sleep-dependent brain oscillations in HD mice, we treated wild-type and symptomatic R6/2 mice acutely with vehicle and paroxetine (5, 10, and 20 mg/kg)...
June 26, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28593439/clinical-and-histopathological-amelioration-of-experimental-autoimmune-encephalomyelitis-by-aav-vectors-expressing-a-soluble-interleukin-23-receptor
#15
Marta Miralles, Herena Eixarch, Marcos Tejero, Carme Costa, Keiji Hirota, A Raul Castaño, Meritxell Puig, Gitta Stockinger, Xavier Montalban, Assumpció Bosch, Carmen Espejo, Miguel Chillon
The role of the T helper (Th)17 pathway has been clearly demonstrated in the onset and progression of autoimmune diseases, where interleukin (IL)-23 is a key molecule in maintaining the response mediated by Th17 cells. As a consequence, recent strategies based on blocking the interaction between IL-23 and its receptor (IL-23R), for example the anti-p19 antibody tildrakizumab, have been developed to regulate the Th17 pathway from the initial stages of the disease. Here, a soluble (s)IL-23R cDNA was cloned in expression plasmids and viral vectors...
June 7, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28585223/a-molecular-tweezer-ameliorates-motor-deficits-in-mice-overexpressing-%C3%AE-synuclein
#16
Franziska Richter, Sudhakar R Subramaniam, Iddo Magen, Patrick Lee, Jane Hayes, Aida Attar, Chunni Zhu, Nicholas R Franich, Nicholas Bove, Krystal De La Rosa, Jacky Kwong, Frank-Gerrit Klärner, Thomas Schrader, Marie-Françoise Chesselet, Gal Bitan
Aberrant accumulation and self-assembly of α-synuclein are tightly linked to several neurodegenerative diseases called synucleinopathies, including idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Deposition of fibrillar α-synuclein as insoluble inclusions in affected brain cells is a pathological hallmark of synucleinopathies. However, water-soluble α-synuclein oligomers may be the actual culprits causing neuronal dysfunction and degeneration in synucleinopathies. Accordingly, therapeutic approaches targeting the toxic α-synuclein assemblies are attractive for these incurable disorders...
June 5, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28560708/tonabersat-prevents-inflammatory-damage-in-the-central-nervous-system-by-blocking-connexin43-hemichannels
#17
Yeri Kim, Jarred M Griffin, Mohd N Mat Nor, Jie Zhang, Peter S Freestone, Helen V Danesh-Meyer, Ilva D Rupenthal, Monica Acosta, Louise F B Nicholson, Simon J O'Carroll, Colin R Green
The cis benzopyran compound tonabersat (SB-220453) has previously been reported to inhibit connexin26 expression in the brain by attenuating the p38-mitogen-activated protein kinase pathway. We show here that tonabersat directly inhibits connexin43 hemichannel opening. Connexin43 hemichannels have been called "pathological pores" based upon their role in secondary lesion spread, edema, inflammation, and neuronal loss following central nervous system injuries, as well as in chronic inflammatory disease. Both connexin43 hemichannels and pannexin channels released adenosine triphosphate (ATP) during ischemia in an in vitro ischemia model, but only connexin43 hemichannels contributed to ATP release during reperfusion...
May 30, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28536850/effectiveness-of-daily-prednisolone-to-slow-progression-of-human-t-lymphotropic-virus-type-1-associated-myelopathy-tropical-spastic-paraparesis-a-multicenter-retrospective-cohort-study
#18
Ariella L G Coler-Reilly, Tomoo Sato, Toshio Matsuzaki, Masanori Nakagawa, Masaaki Niino, Masahiro Nagai, Tatsufumi Nakamura, Norihiro Takenouchi, Natsumi Araya, Naoko Yagishita, Eisuke Inoue, Yoshihisa Yamano
Millions of people are infected with human T-lymphotropic virus type 1 (HTLV-1) worldwide; notable endemic areas include Brazil, the Caribbean islands, Iran, and Japan. A small number of those infected develop the progressive neurodegenerative disease HTLV-1-associated myelopathy (HAM), also known as tropical spastic paraparesis (TSP), which is characterized by chronic spinal cord inflammation and accompanying myelopathic symptoms. The corticosteroid prednisolone (PSL) is a classic treatment for HAM/TSP, yet its effectiveness remains controversial owing to insufficient and conflicting studies...
May 23, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28664299/role-of-disc1-in-neuronal-trafficking-and-its-implication-in-neuropsychiatric-manifestation-and-neurotherapeutics
#19
REVIEW
Toshifumi Tomoda, Takatoshi Hikida, Takeshi Sakurai
Disrupted-in-schizophrenia 1 (DISC1) was initially identified as a gene disrupted by a translocation mutation co-segregating with a variety of psychotic and mood disorders in a Scottish pedigree. In agreement with this original finding, mouse models that perturb Disc1 display deficits of behaviors in specific dimensions, such as cognition and emotion, but not a motor dimension. Although DISC1 is not a risk gene for sporadic cases of specific psychiatric disorders defined by categorical diagnostic criteria (e...
July 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28653280/clozapine-as-a-model-for-antipsychotic-development
#20
REVIEW
Frederick C Nucifora, Marina Mihaljevic, Brian J Lee, Akira Sawa
Schizophrenia is a devastating illness that affects up to 1% of the population; it is characterized by a combination of positive symptoms, negative symptoms, and cognitive impairment. Currently, treatment consists of one class of medications known as antipsychotics, which include typical (first-generation) and atypical (second-generation) agents. Unfortunately, antipsychotic medications have limited efficacy, with up to a third of patients lacking a full response. Clozapine, the first atypical antipsychotic developed, is the only medication shown to be superior to all other antipsychotics...
July 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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