Vision restoration with photoswitch technology

利用光电开关技术恢复视力

• 批准号: 7801340
• 负责人: Andrew Blatz
• 金额: $ 37.45万
• 依托单位: PHOTOSWITCH BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-03 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7801340
• 关键词: Adopted; Affect; Aftercare; Amacrine Cells; Animal Model; Animals; Behavior; Behavioral; Blindness; Cells; Child; Communities; Data; Degenerative Disorder; Development; Development Plans; Dose; Electroretinography; Equipment; Evoked Potentials; Exhibits; Eye; Eye diseases; Figs - dietary; Future; Generations; Goals; Human; Inherited; Injection of therapeutic agent; Ion Channel; Kinetics; Laboratories; Legal patent; Light; Marketing; Measurement; Measures; Medical; Membrane Potentials; Methods; Modeling; Mus; Nature; Neuroglia; Patch-Clamp Techniques; Pathway interactions; Patients; Pattern; Pharmacologic Substance; Phase; Photophobia; Photoreceptors; Physiology; Property; Prosthesis; Protocols documentation; Rare Diseases; Reporting; Research; Resolution; Retina; Retinal; Retinal Cone; Retinal Degeneration; Retinitis Pigmentosa; Rights; Safety; Schools; Small Business Innovation Research Grant; Stimulus; Technology; Testing; Therapeutic; Time; Vertebrate Photoreceptors; Vision; Visual; Zebrafish; assay development; blind; cell type; drug candidate; extracellular; ganglion cell; gene therapy; horizontal cell; improved; in vivo; instrument; meetings; mouse model; mutant; pre-clinical; public health relevance; response; restoration; small molecule; success; theories; therapeutic development; therapeutic target

DESCRIPTION (provided by applicant): Retinitis Pigmentosa (RP) is an inherited disease of the eye that robs its victims of vision. The loss of vision is caused by the degeneration of the rods and cones of the retina while other cells in the retina remain alive. RD is a relatively rare disease, affecting approximately 100,000 people in the US. Approximately 20% of children in schools for the blind suffer from RP. Clearly, the disastrous consequences of RP provide justification for intense research into the causes and potential therapies. Due to the polygenic nature of RP, it does not lend itself to gene therapy or targeted therapeutics. Although some successes in vision restoration using gene therapy have been reported, it is highly unlikely that such therapy will be approved and adopted by the medical community in the near future. An alternative approach to vision restoration for patients with RP, which does not involve gene therapy, is proposed in this Phase I SBIR application where the remaining cells in the damaged retina are made into photosensitive cells using small molecules called "photoswitches". Photoswitches could, in theory, provide resolution approximately a thousand times greater than that of competing video camera prosthetics and will be far less invasive. The four Specific Aims for the first steps along the pathway to an approved therapeutic are (1) Determine which of the many cells in the retina are rendered light-sensitive by the injection of photoswitches into the eyes of blind mice; (2) Demonstrate light-sensitivity in intact mutant blind mice using non-invasive electrophysiological approaches; (3) Demonstrate light-dependent behavior in genetically blind mice after photoswitch treatment; and (4) Determine the optimal parameters for maintaining light-sensitivity in mutant blind mice. The successful completion of this feasibility project will provide justification for the further pursuit of this therapeutic approach to blindness. PUBLIC HEALTH RELEVANCE: Retinitis Pigmentosa (RP) is an inherited disease of the eye that robs its victims of vision. While RD is a relatively rare disease, affecting approximately 100,000 people in the US, approximately 20% of children in schools for the blind suffer from RP. Clearly, the disastrous consequences of RP provide justification for intense research into the causes and potential therapies. Photoswitch Biosciences has developed a technology that has the potential to make healthy cells in the eye into cells that can receive and decode light, restoring sight to sufferers of RP.

描述（由申请人提供）：色素性视网膜炎（RP）是一种遗传性眼部疾病，会导致患者丧失视力。视力丧失是由于视网膜的视杆细胞和视锥细胞退化而引起的，而视网膜中的其他细胞仍然存活。 RD 是一种相对罕见的疾病，影响美国约 10 万人。盲人学校中大约 20% 的儿童患有 RP。显然，RP 的灾难性后果为深入研究其原因和潜在疗法提供了理由。由于 RP 的多基因性质，它不适合基因治疗或靶向治疗。尽管已经报道了使用基因疗法恢复视力的一些成功，但这种疗法在不久的将来不太可能被医学界批准和采用。在这一 I 期 SBIR 应用中，提出了一种不涉及基因治疗的 RP 患者视力恢复替代方法，其中使用称为“光开关”的小分子将受损视网膜中的剩余细胞制成光敏细胞。从理论上讲，光电开关可以提供比竞争摄像机假肢高大约一千倍的分辨率，并且侵入性要小得多。获得批准的治疗方法的第一步有四个具体目标：（1）通过将光开关注射到失明小鼠的眼睛中，确定视网膜中的许多细胞中的哪些细胞对光敏感； (2) 使用非侵入性电生理学方法展示完整突变失明小鼠的光敏感性； (3) 在光开关治疗后展示遗传失明小鼠的光依赖性行为； (4)确定维持突变失明小鼠光敏感性的最佳参数。该可行性项目的成功完成将为进一步追求这种失明治疗方法提供理由。 公众健康相关性：色素性视网膜炎 (RP) 是一种遗传性眼部疾病，会导致患者丧失视力。虽然 RD 是一种相对罕见的疾病，在美国影响大约 10 万人，但盲人学校中大约 20% 的儿童患有 RP。显然，RP 的灾难性后果为深入研究其原因和潜在疗法提供了理由。 Photoswitch Biosciences 开发了一种技术，有可能将眼睛中的健康细胞转化为能够接收和解码光的细胞，从而使 RP 患者恢复视力。