Identification of novel targetable signalling pathways in the inherited ichthyoses

遗传性鱼鳞病中新型靶向信号通路的鉴定

• 批准号: G0901967/1
• 负责人: Priya Dewan
• 金额: $ 29.93万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901967%2F1
• 关键词: Identification; novel; targetable; signalling; pathways

The ichthyoses are a group of rare inherited skin diseases characterised by dry, scaly skin. Ichthyoses have a major impact on quality of life and severe cases can be life-threatening with a major effect on quality of life for both affected child and family. Topical treatments provide limited symptomatic relief only, and available systemic treatments (acitretin and isotretinoin) are not very effective and have major side effects, including an effect on the unborn child. There remains an unmet clinical need for safe and efficacious treatments targeting the different ichthyoses. As the clinical appearance of many of the ichthyoses are similar despite diverse genetic defects, we believe that it may be possible to identify common pathways using engineered skin models with deficiencies in the relevant genes from the same genetic background. High-throughput computer analysis will be used to identify these pathways, which will then be confirmed in patient samples with known defects in the same genes. The identification of new targets in the ichthyoses could encourage drug development in this area and may even allow identification of known drugs that could be used as an alternative to current treatment.

鱼鳞病是一组罕见的遗传性皮肤病，其特征是干燥，鳞状皮肤。鱼鳞病对生活质量有重大影响，严重病例可能危及生命，对受影响儿童和家庭的生活质量有重大影响。局部治疗仅提供有限的症状缓解，并且可用的全身治疗（阿维A和异维甲酸）不是非常有效，并且具有主要副作用，包括对未出生的孩子的影响。针对不同鱼鳞病的安全有效的治疗仍然存在未满足的临床需求。由于许多鱼鳞病的临床表现是相似的，尽管不同的遗传缺陷，我们认为，它可能是可能的，以确定共同的途径，使用工程皮肤模型与缺陷的相关基因，从相同的遗传背景。高通量计算机分析将用于识别这些途径，然后在相同基因中具有已知缺陷的患者样本中进行确认。在鱼鳞病中确定新的靶点可以鼓励这一领域的药物开发，甚至可以确定可用作当前治疗替代品的已知药物。