Current opinion in investigational drugs最新文献_第8页

NLX-P101, an adeno-associated virus gene therapy encoding glutamic acid decarboxylase, for the potential treatment of Parkinson's disease. NLX-P101，一种编码谷氨酸脱羧酶的腺相关病毒基因疗法，用于帕金森病的潜在治疗。

Current opinion in investigational drugs Pub Date : 2010-07-01

Javier Diaz-Nido

{"title":"NLX-P101, an adeno-associated virus gene therapy encoding glutamic acid decarboxylase, for the potential treatment of Parkinson's disease.","authors":"Javier Diaz-Nido","doi":"","DOIUrl":"","url":null,"abstract":"Parkinson's disease (PD) is a neurodegenerative disease affecting nigrostriatal dopaminergic neurons. Dopamine depletion in the striatum leads to functional changes in several deep brain nuclei, including the subthalamic nucleus (STN), which becomes disinhibited and perturbs the control of body movement. Although there is no cure for PD, some pharmacological and surgical treatments can significantly improve the functional ability of patients, particularly in the early stages of the disease. Among neurodegenerative diseases, PD is a particularly suitable target for gene therapy because the neuropathology is largely confined to a relatively small region of the brain. Neurologix Inc is developing NLX-P101 (AAV2-GAD), an adeno-associated viral vector encoding glutamic acid decarboxylase (GAD), for the potential therapy of PD. As GAD potentiates inhibitory neurotransmission from the STN, sustained expression of GAD in the STN by direct delivery of NLX-P101 decreases STN overactivation. This procedure was demonstrated to be a safe and efficient method of reducing motor deficits in animal models of PD. A phase I clinical trial has demonstrated that NLX-P101 was safe and indicated the efficacy of this approach in patients with PD. Results from an ongoing phase II clinical trial of NLX-P101 are awaited to establish the clinical efficacy of this gene therapy.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 7","pages":"813-22"},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29075228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cognitive effects of muscarinic M1 functional agonists in non-human primates and clinical trials. 毒蕈碱M1功能激动剂在非人灵长类动物中的认知作用及临床试验。

Current opinion in investigational drugs Pub Date : 2010-07-01

Robert A McArthur, Julian Gray, Rudy Schreiber

{"title":"Cognitive effects of muscarinic M1 functional agonists in non-human primates and clinical trials.","authors":"Robert A McArthur, Julian Gray, Rudy Schreiber","doi":"","DOIUrl":"","url":null,"abstract":"The limited effect of AChE inhibitors and NMDA receptor antagonists for the treatment of the cognitive symptoms of Alzheimer's disease has prompted the search for new drugs that are capable not only of treating behavioral symptoms, but also of modifying the disease process. Considerable research efforts have been focused on orthosteric muscarinic M1 functional agonists during the past decade to address both these strategies. Part of this research has included the use of non-human primates as models of cognitive impairment to demonstrate preclinical efficacy. No M1 functional agonist has been successfully registered for the treatment of Alzheimer's disease, mostly because of mechanism-related adverse side effects and marginal cognitive effects. However, the M1 agonist xanomeline exhibited preclinical and clinical efficacy for the treatment of the negative and cognitive symptoms of schizophrenia. These results prompted renewed interest in repositioning compounds such as sabcomeline (Proximagen Group plc) for this indication, as well as developing allosteric muscarinic M1 ligands to improve efficacy while reducing side-effect-related attrition. This review discusses preclinical and clinical data from orthosteric M1 functional agonists, focusing on target validation in primate cognition studies, and provides recommendations for testing a new generation of M1 ligands and compounds with novel mechanisms of action.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 7","pages":"740-60"},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29077401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vismodegib, a small-molecule inhibitor of the hedgehog pathway for the treatment of advanced cancers. Vismodegib，一种用于治疗晚期癌症的小分子hedgehog通路抑制剂。