HSV GAD for Painful Diabetic Neuropathy

HSV GAD 治疗疼痛性糖尿病神经病变

• 批准号: 8466768
• 负责人: DAVID J. FINK
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8466768
• 关键词: Advisory Committees; Animal Experiments; Animals; Behavior; Biodistribution; Butyric Acids; Cancer Etiology; Certification; Clinical Protocols; Clinical Trials; Contracts; Cyclic GMP; Development; Diabetic Neuralgia; Engineering; Enkephalins; Enrollment; Funding; GMP lots; Gene Delivery; Glutamate Decarboxylase; Goals; Grant; HSV vector; Human; Institutional Review Boards; Intractable Pain; Ion Channel; Legal patent; Ligation; Malignant Neoplasms; Michigan; Modeling; Nervous system structure; Neurotransmitter Receptor; Neurotransmitters; Nociception; Opioid Peptide; Ownership; Pain; Pathway interactions; Patients; Phase; Phase I Clinical Trials; Production; Recombinant DNA; Rodent Model; Series; Simplexvirus; Site; Skin; Solid; Spinal Ganglia; Spinal cord posterior horn; Spinal nerve structure; Testing; Time; Toxicology; Translational Research; Universities; Validation; Vertebral column; Viral; Work; abstracting; animal data; animal efficacy; base; cGMP production; cancer pain; cell bank; chronic pain; design; effective therapy; endomorphin 2; experience; inflammatory pain; neurotransmission; novel; painful neuropathy; pre-clinical; preproenkephalin; programs; small molecule; vector

DESCRIPTION (provided by applicant): Abstract: We are applying to the RR&D Cooperative Program in Translational Research to seek funding to complete the preclinical steps required to obtain IND and IRB approval of a glutamic acid decarboxylase (GAD)-expressing herpes simplex virus (HSV)-based vector for a phase 1/2 clinical trial in patients with painful diabetic neuropathy (PDN). The development of novel effective treatments for chronic pain has been disappointingly slow, in part because the conservative use of a limited repertoire of neurotransmitters, receptors and ion channels in the nervous limits our ability to employ systemically administered small molecules to selectively interrupt nociceptive neurotransmission. To overcome this limitation we have constructed a series of non- replicating HSV-based vectors that efficiently target gene delivery to dorsal root ganglia from skin inoculation to effect the release of antinociceptive neurotransmitters in dorsal horn of spinal cord. We have taken the first of these vectors - a nonreplicating HSV vector expressing preproenkephalin - into phase 1 clinical trial in patients with intractable pain from cancer. There is a substantial unmet need for effective treatments of neuropathic pain; preclinical animal studies demonstrate that the GAD-expressing HSV vector is effective in a rodent model of PDN; and the VA has an ownership stake in the patent (under review) for this vector. Successful completion of the work proposed will allow the vector to be tested in patients.

描述（由申请人提供）：