Novel Treatment for Parkinson's Disease

帕金森病的新疗法

• 批准号: 7326049
• 负责人: Dale J Christensen
• 金额: $ 29.03万
• 依托单位: COGNOSCI, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7326049
• 关键词: 1-Methyl-4-phenylpyridinium; Address; Affect; Age of Onset; Alleles; American; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Apolipoprotein E; Apoptosis; Apoptotic; Astrocytes; Behavioral; Behavioral Assay; Biochemical; Biological Assay; Bradykinesia; Brain; Brain Chemistry; Caring; Cell Line; Clinical; Common Cold; Control Animal; Data; Development; Diagnosis; Disease; Disease Progression; Disease model; Dopamine; Dose; Elderly; Enzymes; Excitatory Neurotoxins; Exhibits; Family; Free Radicals; Funding; Genes; Genetic; Glutamates; Goals; Immunochemistry; Incidence; Inflammation; Inflammatory; Inhibition of Apoptosis; Interleukin-6; Investigation; JNK-activating protein kinase; Lead; Levodopa; Limb structure; Lipopolysaccharides; MAPK14 gene; Macrophage Activation; Measures; Mediator of activation protein; Microglia; Mitogen-Activated Protein Kinases; Modeling; Monitor; Multiple Sclerosis; Multiple Trauma; Mus; N-Methylaspartate; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Numbers; Outcome; Outcome Measure; Oxidative Stress; Oxidopamine; Palliative Care; Parkinson Disease; Patients; Peptides; Performance; Pesticides; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Phosphorylation; Phosphotransferases; Play; Population; Production; Proteins; Quality of life; Rattus; Reporting; Research; Role; Severities; Shuffling Gaits; Signal Transduction; Signaling Molecule; Signaling Protein; Societies; Substantia nigra structure; Symptoms; TNF gene; Testing; Therapeutic; Toxin; Traumatic Brain Injury; Tremor; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Western Blotting; Work; base; behavior measurement; behavior test; caspase-8; cytokine; dopaminergic neuron; excitotoxicity; human TNF protein; human disease; improved; in vivo; insight; mouse model; neuron apoptosis; neuron loss; neuroprotection; novel; novel strategies; novel therapeutics; release factor; research study; response; success; synuclein

DESCRIPTION (provided by applicant): Parkinson's Disease (PD) is a devastating neurodegenerative disorder that affects approximately 500,000 people in the US and an additional 50,000 are diagnosed each year. This disease is characterized by tremors in the limbs, bradykinesia, akinesia, rigid limbs, and a shuffling gait. The symptoms of PD are caused by the destruction of dopaminergic neurons in the substantia nigra, leading to a severe reduction in dopamine concentrations within the brain. PD treatment is currently more like a common cold, with drugs that alleviate symptoms but do not address the underlying cause of the disease. Unfortunately, this approach does nothing to reduce neurodegeneration of dopaminergic neurons such that the severity of PD increases. Any new treatment that provides neuroprotection and eliminates neurodegeneration would provide a fundamental improvement over current treatments. Recent research indicates that inflammation plays a significant role in development of PD. In addition, there are a number of reports that characterize genetic factors that influence the disease progression and incidence. The protein apolipoprotein E (ApoE) provides a convergence point for these factors. Several reports implicate the e4 allele of ApoE as playing a critical role in the age of onset for development of PD. In addition, ApoE has been shown to have significant anti-inflammatory effects within the brain. Cognosci Inc. has investigated the anti-inflammatory effects of ApoE for several years and have documented some of the mechanisms of anti-inflammatory and neuroprotective effects of ApoE and derivatives. These investigations have lead to isolation of an anti-inflammatory/neuroprotective peptide, COG133, that may be an effective therapeutic for neurodegenerative disease. In this proposal, we will test COG133 for treatment of PD via a novel mechanism. This approach to PD therapeutics represents a paradigm shift in the development of PD therapeutics. The goal of the proposed project entitled "Novel Therapy for Parkinson's Disease" is to evaluate a novel approach to treatment of a debilitating disease that presently affects over 500,000 predominantly elderly Americans. Advances made through the proposed project could lead to new therapies that reduce the debilitating effects of the disease and lessen the burden on society in caring for those who cannot care for themselves. Success in development of new therapeutics will also provide for a potentially significant increase in quality of life for affected patients and their families.

描述（由申请人提供）：帕金森病（PD）是一种毁灭性的神经退行性疾病，在美国影响约50万人，每年诊断出另外5万人。这种疾病的特征是四肢震颤、运动迟缓、运动不能、四肢僵硬和拖着脚走路。PD的症状是由黑质中多巴胺能神经元的破坏引起的，导致大脑内多巴胺浓度严重降低。PD治疗目前更像是普通感冒，药物可以缓解症状，但不能解决疾病的根本原因。不幸的是，这种方法不能减少多巴胺能神经元的神经变性，从而增加PD的严重程度。任何提供神经保护和消除神经退行性变的新治疗方法都将比目前的治疗方法提供根本性的改善。最近的研究表明，炎症在PD的发展中起着重要作用。此外，还有一些报告描述了影响疾病进展和发病率的遗传因素。蛋白质载脂蛋白E（ApoE）提供了这些因子的汇聚点。一些报道暗示ApoE的e4等位基因在PD发病年龄中起关键作用。此外，ApoE已被证明在大脑中具有显着的抗炎作用。Cognosci Inc.研究ApoE的抗炎作用已有数年，并且已经记录了ApoE及其衍生物的抗炎和神经保护作用的一些机制。这些研究已经导致了抗炎/神经保护肽COG 133的分离，其可能是神经退行性疾病的有效治疗剂。在这项提案中，我们将通过一种新的机制测试COG 133治疗PD。这种PD治疗方法代表了PD治疗发展的范式转变。该项目的目标是评估一种新的方法来治疗一种目前影响50多万主要是老年美国人的衰弱性疾病。通过拟议项目取得的进展可能导致新的疗法，减少疾病的衰弱影响，减轻社会在照顾那些不能照顾自己的人方面的负担。新疗法的成功开发也将为受影响的患者及其家属的生活质量提供潜在的显着提高。