Abstract：
BACKGROUND:Spinal muscular atrophy (SMA) is a fatal motor neuron disease of childhood that is caused by mutations in the SMN1 gene. Currently, no effective treatment is available. One possible therapeutic approach is the use of antisense oligos (ASOs) to redirect the splicing of the paralogous gene SMN2, thus increasing functional SMN protein production. Various ASOs with different chemical properties are suitable for these applications, including a morpholino oligomer (MO) variant with a particularly excellent safety and efficacy profile. OBJECTIVE:We investigated a 25-nt MO sequence targeting the negative intronic splicing silencer (ISS-N1) 10 to 34 region. METHODS:We administered a 25-nt MO sequence against the ISS-N1 region of SMN2 (HSMN2Ex7D[-10-34]) in the SMAΔ7 mouse model and evaluated the effect and neuropathologic phenotype. We tested different concentrations (from 2 to 24 nM) and delivery protocols (intracerebroventricular injection, systemic injection, or both). We evaluated the treatment efficacy regarding SMN levels, survival, neuromuscular phenotype, and neuropathologic features. RESULTS:We found that a 25-nt MO sequence against the ISS-N1 region of SMN2 (HSMN2Ex7D[-10-34]) exhibited superior efficacy in transgenic SMAΔ7 mice compared with previously described sequences. In our experiments, the combination of local and systemic administration of MO (bare or conjugated to octaguanidine) was the most effective approach for increasing full-length SMN expression, leading to robust improvement in neuropathologic features and survival. Moreover, we found that several small nuclear RNAs were deregulated in SMA mice and that their levels were restored by MO treatment. CONCLUSION:These results indicate that MO-mediated SMA therapy is efficacious and can result in phenotypic rescue, providing important insights for further development of ASO-based therapeutic strategies in SMA patients.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Nizzardo M,Simone C,Salani S,Ruepp MD,Rizzo F,Ruggieri M,Zanetta C,Brajkovic S,Moulton HM,Müehlemann O,Bresolin N,Comi GP,Corti Sdoi
10.1016/j.clinthera.2014.02.004subject
Has Abstractpub_date
2014-03-01 00:00:00pages
340-56.e5issue
3eissn
0149-2918issn
1879-114Xpii
S0149-2918(14)00073-3journal_volume
36pub_type
杂志文章abstract：PURPOSE:The effects of air pollutants have been receiving increased attention both clinically and in the media. One such pollutant is mold, fungal growth in the form of multicellular filaments known as hyphae. The growth of molds is omnipresent not only in outdoor settings but also in indoor environments containing exc...
journal_title：Clinical therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.clinthera.2018.05.004
更新日期：2018-06-01 00:00:00
abstract：BACKGROUND:Varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, has been developed specifically for smoking cessation. In Japan, 39.3% of men smoke and this is a major public health concern. OBJECTIVE:The primary objective of this study was to evaluate the efficacy and dose-response r...
journal_title：Clinical therapeutics
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1016/j.clinthera.2007.06.012
更新日期：2007-06-01 00:00:00
abstract：:Twenty-seven Escherichia coli test strains that were not susceptible to cephalothin were tested for susceptibility to cefazolin, cefamandole, and ceforanide. By zone-size criteria (greater than or equal to 18 mm), 67% of E coli were susceptible to cefazolin and cefamandole, and 93% were susceptible to ceforanide. By m...
journal_title：Clinical therapeutics
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：BACKGROUND:It has been reported that the efficacy of acute forms of nicotine replacement therapy, such as nicotine gum and lozenges, improves when sufficient quantities of medication are used. OBJECTIVE:This analysis examined whether adherence with daily nicotine patch wear was associated with improved rates of smokin...
journal_title：Clinical therapeutics
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.clinthera.2008.09.016
更新日期：2008-10-01 00:00:00
abstract：BACKGROUND:Mycophenolate mofetil (MMF) is an immunosuppressant indicated for prophylaxis of acute organ transplant rejection. Generic MMF is less costly than the branded product, but European regulatory authorities require bioequivalence studies for the marketing of generics. OBJECTIVES:The aims of the 2 studies repor...
journal_title：Clinical therapeutics
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.clinthera.2011.04.003
更新日期：2011-03-01 00:00:00
abstract：BACKGROUND:Postoperative nausea and vomiting (PONV) are distressing and frequent adverse effects (AEs) in women undergoing laparoscopic gynecologic surgery. Midazolam has been reported to be effective for preventing PONV in adults undergoing middle ear surgery and children undergoing strabismus surgery or tonsillectomy...
journal_title：Clinical therapeutics
pub_type： 杂志文章,随机对照试验,收录出版
doi：10.1016/j.clinthera.2010.08.005
更新日期：2010-08-01 00:00:00
abstract：OBJECTIVE:This post hoc analysis was aimed to summarize the efficacy and tolerability of duloxetine as represented by number needed to treat (NNT) and number needed to harm (NNH) to provide a clinically useful assessment of the position of duloxetine among current agents used to treat diabetic peripheral neuropathic pa...
journal_title：Clinical therapeutics
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1016/j.clinthera.2007.12.002
更新日期：2007-01-01 00:00:00
abstract：BACKGROUND:Rates of patient adherence (compliance) to pharmacotherapy range from <5% to >90%. Negative determinants include multiple daily dosing (MDD), chronic duration, and asymptomatic disease. Reports suggest that once-daily (QD) dosing may improve adherence, but their findings are inconclusive. OBJECTIVE:The purp...
journal_title：Clinical therapeutics
pub_type： 杂志文章,meta分析
doi：10.1016/s0149-2918(02)85026-3
更新日期：2002-02-01 00:00:00
abstract：INTRODUCTION:Acute generalized exanthematous pustulosis (AGEP) is a clinical reaction pattern that is principally drug induced and is characterized by acute, extensive formation of nonfollicular sterile pustules on an erythematous and edematous substrate. Hydroxychloroquine (HHCQ), an antimalarial drug widely used to t...
journal_title：Clinical therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.clinthera.2008.05.014
更新日期：2008-05-01 00:00:00
abstract：BACKGROUND:Amlodipine is a third-generation dihydropyridine calcium antagonist for the treatment of angina and hypertension. The relative bioavailability of a newly developed dispersible tablet as compared with an established branded formulation has not been reported in a Chinese population. OBJECTIVE:The aim of this ...
journal_title：Clinical therapeutics
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.clinthera.2009.04.013
更新日期：2009-04-01 00:00:00
abstract：BACKGROUND:Most patients with hypertension in the United States and Europe fail to achieve the recommended target blood pressure (BP) of <140/90 mm Hg. Combination therapy is required in approximately two thirds of all patients whose BP is >20/10 mm Hg above the goal. Combination therapy with agents having complementar...
journal_title：Clinical therapeutics
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1016/j.clinthera.2007.02.003
更新日期：2007-02-01 00:00:00
abstract：OBJECTIVES:The primary study objective was to assess the time course and intensity of sedation after administration of immediate-release (IR) and extended-release (XR) quetiapine fumarate in healthy subjects during dose initiation. The tolerability of the 2 formulations was also evaluated. METHODS:This was a randomize...
journal_title：Clinical therapeutics
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.clinthera.2009.03.002
更新日期：2009-03-01 00:00:00
abstract：BACKGROUND:Mirodenafil is a phosphodiesterase type 5 (PDE-5) inhibitor developed for the treatment of erectile dysfunction. Mirodenafil has the possibility of being administered with alcohol. OBJECTIVE:This study assessed the hemodynamic effects and pharmacokinetic properties of mirodenafil administered with alcohol. ...
journal_title：Clinical therapeutics
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.clinthera.2009.06.008
更新日期：2009-06-01 00:00:00
abstract：OBJECTIVE:The aim of this study was to characterize comprehensive medication therapy management (MTM) involving a community pharmacy and local physicians by describing the drug-related issues encountered, identifying which medication types were associated with these issues, and listing the actions taken by physicians a...
journal_title：Clinical therapeutics
pub_type： 杂志文章
doi：10.1016/s0149-2918(05)00146-3
更新日期：2005-07-01 00:00:00
abstract：:A total of 128 corticosteroid-independent adults with chronic allergic asthma were treated for six weeks with 400 micrograms/day of beclomethasone dipropionate aerosol. Most patients (114 or 89%) had a good to excellent response, characterized by a marked improvement in the signs and symptoms of asthma. Substantial im...
journal_title：Clinical therapeutics
pub_type： 杂志文章
doi：
更新日期：1982-01-01 00:00:00
abstract：:This paper briefly reviews the extent of current drug coverage for Medicare beneficiaries and describes the most important issues faced by aged beneficiaries who receive or seek drug coverage through a Medicare managed care plan. Changes in payment rates to these plans as a result of the Balanced Budget Act of 1997 ma...
journal_title：Clinical therapeutics
pub_type： 杂志文章
doi：10.1016/s0149-2918(98)80123-9
更新日期：1998-11-01 00:00:00
abstract：BACKGROUND:Patients newly diagnosed with type 2 diabetes mellitus generally initiate therapy with either metformin [Met] or a sulfonylurea [SU] drug, followed by the addition of a second agent (Met, an SU drug, or a thiazolidinedione [TZD] drug) if the diabetes is not well controlled. If necessary, the usual third line...
journal_title：Clinical therapeutics
pub_type： 杂志文章
doi：10.1016/j.clinthera.2011.10.018
更新日期：2011-12-01 00:00:00
abstract：BACKGROUND:Belimumab, a monoclonal antibody that inhibits B-lymphocyte stimulating protein, was the first biologic agent approved for, and the first drug approved in 55 years for, the treatment of systemic lupus erythematosus (SLE) by the US Food and Drug Administration (FDA). OBJECTIVE:This article reviews the curren...
journal_title：Clinical therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.clinthera.2012.02.028
更新日期：2012-05-01 00:00:00
abstract：:Community-acquired pneumonia (CAP) is responsible for an average of 4.5 million visits annually to physicians' offices, emergency departments, and outpatient clinics. However, there have been few studies using national data on the costs of treating CAP. Without such data, it is difficult to assess whether new therapie...
journal_title：Clinical therapeutics
pub_type： 杂志文章
doi：10.1016/s0149-2918(98)80144-6
更新日期：1998-07-01 00:00:00
abstract：BACKGROUND:Linezolid is available in an oral as well as an intravenous formulation. It is an oxazolidinone antibiotic and is effective in treating resistant gram-positive organisms such as methicillin-resistant Staphylococcus aureus and multidrug-resistant Streptococcus pneumoniae. OBJECTIVES:The goals of this study w...
journal_title：Clinical therapeutics
pub_type： 杂志文章
doi：10.1016/S0149-2918(10)80027-X
更新日期：2010-12-01 00:00:00
abstract：OBJECTIVES:This study was conducted to estimate the prevalence of antipsychotic polypharmacy among fee-for service state Medicaid beneficiaries initiating antipsychotic drug therapy and to investigate psychiatric and demographic predictors of such polypharmacy. METHODS:This was a retrospective cohort study employing M...
journal_title：Clinical therapeutics
pub_type： 杂志文章
doi：10.1016/j.clinthera.2007.01.002
更新日期：2007-01-01 00:00:00
abstract：OBJECTIVES:The aims of this study were to determine the prevalence of prescribing potentially inappropriate medications (PIMs) based on the 2002 Beers criteria among ambulatory patients aged > or =65 years, to compare PIM prevalence rates based on the 1997 Beers criteria and Zhan criteria with the rate obtained using t...
journal_title：Clinical therapeutics
pub_type： 杂志文章
doi：10.1016/j.clinthera.2005.01.009
更新日期：2005-01-01 00:00:00
abstract：:Pregnancy creates a climate favorable to the growth of Candida albicans, and this yeast often is difficult to eradicate in pregnant women. Miconazole nitrate administered intravaginally has been found to achieve comparable therapeutic and mycological cure rates in both pregnant and nonpregnant women. A number of clini...
journal_title：Clinical therapeutics
pub_type： 杂志文章
doi：
更新日期：1986-01-01 00:00:00
abstract：BACKGROUND:Reduction in plasma low-density lipoprotein cholesterol (LDL-C) is a fundamental treatment for the prevention of acute coronary syndromes (ACS). Although statin therapy confers significant protection against ACS in both primary and secondary prevention, a considerable residual risk remains after intensive th...
journal_title：Clinical therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.clinthera.2013.06.019
更新日期：2013-08-01 00:00:00
abstract：:Neisseria microorganisms (Neisseria lactamica, Neisseria sicca, and Neisseria mucosa) are regarded as normal respiratory commensals. Branhamella catarrhalis (formerly Neisseria catarrhalis) has also been regarded as a normal respiratory commensal, but reports indicate that it can be pathogenic. The role of Neisseria s...
journal_title：Clinical therapeutics
pub_type： 杂志文章
doi：
更新日期：1989-09-01 00:00:00
abstract：:The efficacy and tolerability of a twice-daily dose of 5 mg of nisoldipine versus 40 mg of sustained-release isosorbide dinitrate (ISDN) were compared in a randomized, double-masked study in 91 patients. During the 21-day treatment period, the mean time taken during bicycle ergometry to the appearance of an ST segment...
journal_title：Clinical therapeutics
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/s0149-2918(96)80025-7
更新日期：1996-05-01 00:00:00
abstract：BACKGROUND:Although the metabolic effects of the thiazolidinediones have been well studied, there is a lack of comparative data on their effects on certain cardiovascular risk factors, such as elevated plasma levels of lipoprotein (a) (Lp[a]) and homocysteine (Hcy). OBJECTIVE:This study compared the effects of pioglit...
journal_title：Clinical therapeutics
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1016/j.clinthera.2006.05.012
更新日期：2006-05-01 00:00:00
abstract：BACKGROUND:In vitro studies have demonstrated that ticagrelor, an oral antiplatelet agent, is a substrate, activator, and inhibitor of cytochrome P450 (CYP) 3A. Thus, potential CYP3A-mediated drug-drug interactions may occur. OBJECTIVES:The goal of this article was to report study results on the effect of ticagrelor o...
journal_title：Clinical therapeutics
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/j.clinthera.2013.06.003
更新日期：2013-07-01 00:00:00
abstract：BACKGROUND:Danazol is a synthetic androgen derivative frequently used as prophylaxis in patients with hereditary angioedema (HAE) due to complement-1 esterase inhibitor deficiency. However, danazol has been reported to decrease high-density lipoprotein cholesterol (HDL-C) levels and to adversely affect coagulation para...
journal_title：Clinical therapeutics
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.clinthera.2008.12.021
更新日期：2008-12-01 00:00:00
abstract：BACKGROUND:Many patients and physicians interpret episodic headache in the presence or absence of nasal symptoms as "sinus' headache, while ignoring the possible diagnosis of migraine. OBJECTIVE:The purpose of this study was to assess the efficacy and tolerability of sumatriptan succinate 50-mg tablets in patients wit...
journal_title：Clinical therapeutics
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1016/j.clinthera.2007.01.012
更新日期：2007-01-01 00:00:00
