Identification of novel targetable signalling pathways in the inherited ichthyoses

鱼鳞病是一组罕见的遗传性皮肤病，以干燥、鳞状皮肤为特征。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都有重大影响。局部治疗只能提供有限的症状缓解，而可用的全身治疗(阿维A和异维A酸)不是很有效，并且有主要的副作用，包括对未出生的孩子的影响。对于针对不同鱼鳞病的安全和有效的治疗，临床需求仍然没有得到满足。由于许多鱼鳞病的临床表现相似，尽管存在不同的遗传缺陷，我们相信使用具有相同遗传背景的相关基因缺陷的工程皮肤模型来识别共同的路径是可能的。高通量计算机分析将被用来识别这些途径，然后将在具有相同基因已知缺陷的患者样本中得到确认。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方法的替代药物的已知药物。

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.