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    INTRAVENTRICULAR PROTEIN DELIVERY FOR AMYOTROPHIC LATERAL SCLEROSIS
    1.
    发明申请
    INTRAVENTRICULAR PROTEIN DELIVERY FOR AMYOTROPHIC LATERAL SCLEROSIS 审中-公开
    宫内膜间质性输卵管造影

    公开(公告)号：US20090105141A1

    公开(公告)日：2009-04-23

    申请号：US12175870

    申请日：2008-07-18

    申请人： James Dodge ,  Ronald K. Scheule

    发明人： James Dodge ,  Ronald K. Scheule

    IPC分类号： A61K38/18 ,  A61P25/00

    CPC分类号： A61K38/30

    摘要： Amyotrophic Lateral Sclerosis can be successfully treated using intraventricular delivery of a neurotrophic growth factor, IGF-1. The administration can be performed slowly to achieve maximum effect. Effects are seen on both sides of the blood-brain barrier, making this a delivery means for Amyotrophic Lateral Sclerosis which affects both brain and skeletal muscle.

    摘要翻译： 肌营养不良性侧索硬化可以使用神经营养生长因子IGF-1的脑室内输送成功治疗。 可以缓慢执行给药以达到最大效果。 在血脑屏障的两侧看到效果，这是影响脑和骨骼肌的肌萎缩性侧索硬化的递送手段。

    Cationic amphiphiles for intracellular delivery of therapeutic molecules
    2.
    发明授权
    Cationic amphiphiles for intracellular delivery of therapeutic molecules 有权
    阳离子两亲物用于细胞内递送治疗分子

    公开(公告)号：US06383814B1

    公开(公告)日：2002-05-07

    申请号：US09228232

    申请日：1999-01-11

    申请人： Edward R. Lee ,  David J. Harris ,  Craig S. Siegel ,  Mathieu B. Lane ,  Shirley C. Hubbard ,  Seng H. Cheng ,  Simon J. Eastman ,  John Marshall ,  Ronald K Scheule ,  Nelson S. Yew

    发明人： Edward R. Lee ,  David J. Harris ,  Craig S. Siegel ,  Mathieu B. Lane ,  Shirley C. Hubbard ,  Seng H. Cheng ,  Simon J. Eastman ,  John Marshall ,  Ronald K Scheule ,  Nelson S. Yew

    IPC分类号： C12N1588

    CPC分类号： C12N15/88 ,  A61K9/1272 ,  A61K47/542 ,  A61K47/543 ,  A61K47/554 ,  A61K48/00 ,  C07J41/0005 ,  C07J41/0055 ,  C07J41/0061 ,  C07J43/003

    摘要： Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.

    摘要翻译： 提供了新的阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。 两亲物含有衍生自类固醇的单亲或二烷基胺或烷基或酰基的亲脂基团; 和在生理pH下可质子化的阳离子基团，衍生自胺，烷基胺或多烷基胺。 还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。 根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。 本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。 关于用于基因治疗的治疗组合物，DNA通常以用于与阳离子两亲物络合的质粒的形式提供。还公开了新的和高效的质粒构建体，包括在为临床条件提供基因治疗方面特别有效的 炎症复杂。 此外，描述了通过静脉内施用治疗组合物靶向用于基因治疗的器官。

    SYSTEMIC INSULIN-LIKE GROWTH FACTOR-1 THERAPY REDUCES DIABETIC PERIPHERAL NEUROPATHY AND IMPROVES RENAL FUNCTION IN DIABETIC NEPHROPATHY
    10.
    发明申请
    SYSTEMIC INSULIN-LIKE GROWTH FACTOR-1 THERAPY REDUCES DIABETIC PERIPHERAL NEUROPATHY AND IMPROVES RENAL FUNCTION IN DIABETIC NEPHROPATHY 审中-公开
    系统性胰岛素样生长因子-1治疗可减少糖尿病性外周神经病变，改善糖尿病患者的肾功能

    公开(公告)号：US20100216709A1

    公开(公告)日：2010-08-26

    申请号：US12609115

    申请日：2009-10-30

    申请人： Ronald K. Scheule ,  Qiuming CHU

    发明人： Ronald K. Scheule ,  Qiuming CHU

    IPC分类号： A61K38/30 ,  A61P25/02 ,  A61K31/7088

    CPC分类号： A61K38/30 ,  A61K48/00 ,  C12N15/86 ,  C12N2750/14143 ,  C12N2830/008

    摘要： The present invention provides methods of treatment of patients suffering from the complications of blood sugar disorders: diabetic peripheral neuropathy and diabetic nephropathy by administration of IGF-1 via protein therapy or gene therapy. It relates to methods of treating an individual having a diabetic disorder or a hyperglycemic disorder, comprising administering to the individual an effective amount of a DNA vector expressing IGF-1Eb or IGF-1Ec in vivo or an effective amount of at the IGF-1Eb or IGF-1Ec protein in the early hyperalgesia stage or in patients that have advanced to the hyposensitivity stage. Treatment at the early hyperalgesia stage prevents subsequent hyposensitivity with increases or maintenance of sensory nerve function. IGF-1Eb or IGF-1Ec treatment also increases muscle mass and improves overall mobility, which indicates a treatment-related improvement in motor function. Treatment with IGF-1Eb or IGF-1Ec at the hyposensitivity stage reverses hyposensitivity and improves muscle mass and overall health. Systemic IGF-1 provides a therapeutic modality for treating hyposensitivity associated with DPN. In addition, IGF-1Eb or IGF-1Ec provides a therapeutic modality for treating diabetic nephropathy. IGF-1Eb or IGF-1Ec improves renal function as evidenced by a modulation in serum albumin concentration and a reduction in urine volume and protein levels. IGF-1Eb or IGF-1Ec also reduces diabetic glomerulosclerosis.

    摘要翻译： 本发明提供了通过蛋白质治疗或基因治疗施用IGF-1来治疗患有血糖紊乱并发症的患者的糖尿病性周围神经病变和糖尿病性肾病的方法。 本发明涉及治疗患有糖尿病病症或高血糖病症的个体的方法，包括向个体施用有效量的体内表达IGF-1Eb或IGF-1Ec的DNA载体或在IGF-1Eb或 IGF-1Ec蛋白在早期痛觉过敏阶段或患有进展至低敏感期的患者。 在早期痛觉过敏阶段的治疗可以通过增加或维持感觉神经功能阻止随后的敏感性。 IGF-1Eb或IGF-1Ec治疗也增加肌肉质量并改善整体移动性，这表明运动功能的治疗相关改善。 IGF-1Eb或IGF-1Ec在过敏反应阶段的治疗反转了敏感性，改善了肌肉质量和整体健康。 系统性IGF-1提供治疗与DPN相关的敏感性的治疗方式。 此外，IGF-1Eb或IGF-1Ec提供治疗糖尿病性肾病的治疗方法。 IGF-1Eb或IGF-1Ec可改善肾功能，如血清白蛋白浓度的调节和尿量和蛋白质水平的降低所证明。 IGF-1Eb或IGF-1Ec还可减少糖尿病肾小球硬化。