A phase 2 placebo-controlled clinical trial with ACU-4429 (visual cycle modulator) for the treatment of dry age related macular degeneration (AMD): effect on drusen volume, measured with an optical coherence tomography device and a newly developed algorit

提出的研究项目的目的是找到一种治疗非渗出性（干性）年龄相关性黄斑变性（AMD）的方法，这是目前无法治疗的，与湿性形式的疾病相比。AMD是一种慢性退行性视网膜疾病，是工业化国家老年人（50岁以上）失明的主要原因。干性AMD影响大约。到目前为止，90%的amd患者没有治疗选择。我的研究项目的目标是启动一项安慰剂对照的2期临床试验，ACU-4429（视觉周期调节剂）作为口服药物治疗干性AMD及其对dren生长的影响，因为dren是AMD的最初迹象。ACU-4429是一种异构酶复合物（RPE-65）抑制剂，一项针对健康受试者的i期临床试验显示，ACU-4429对视网膜色素上皮细胞（RPE）中有毒终产物的积累有影响。因此，ACU-4429可能影响肾小球的发展，并影响疾病的进程。德鲁森体积是本研究的一个重要终点，它是用一种新开发的算法测量的，该算法包含在卷云光谱域光学相干断层扫描设备（SD-OCT）中。该算法生成患者的真实RPE和虚拟RPE（没有任何变形）之间的差值图，从而产生德鲁斯-体积图。考虑到自然的猪动态，ACU-4429对猪生长的影响（疾病进展的标志）可以用该算法来衡量。该项目的假设是用ACU-4429药物阻止或至少延缓干性AMD的进展。

The intention of the presented research project is to find a treatment for non-exudative (dry) Age Related Macular Degeneration (AMD), which is currently not treatable, in contrast to the wet form of the disease. AMD is a chronic degenerative retinal disease and the leading cause of blindness in the elderly (over 50 years of age) of the industrialized world. Dry AMD affects approx. 90 % of all AMD-patients, who so far do not have a therapeutic option. The goal of my research project is to initiate a placebo-controlled phase 2 clinical trial with ACU-4429 (visual cycle modulator) as oral medication for the treatment of dry AMD and its effect on drusen growth as drusen are first signs of AMD. ACU-4429 is an isomerase-complex (RPE-65)-inhibitor, and a first phase 1 clinical trial on healthy subjects showed an effect on the accumulation of toxic end-products in the retinal pigment epithelial cell (RPE). ACU-4429 could therefore affect the development of drusen, and influence the course of the disease. Drusen volume is an important endpoint of the presented study and is measured with a newly developped algorithm incorporated in the Cirrus spectral domain optical coherence tomography device (SD-OCT). This algorithm generates a difference map between the real RPE of a patient and a virtuell RPE (free of any deformation), resulting in a drusen-volume map. Considering natural drusen dynamic, an effect of ACU-4429 on drusen growth (sign for disease progression) can be measured with this algorithm. The hypothesis of the project is to stop or at least to retard dry AMD progression with ACU-4429 medication.