Development of a Novel Gene Therapy for Neurodegenerative Diseases

肌萎缩侧索硬化症(ALS)是一种致命的运动神经元疾病，患者在确诊后3-5年内死亡。利鲁唑是英国唯一被批准将生存期延长6个月的药物。对肌萎缩侧索硬化症的病理生理学研究的增加使人们对疾病进展的分子机制有了更深入的了解。最近，已经确定了几个令人兴奋的目标。使用传统的基于小分子和单抗的方法，这些靶点中的许多是不能下药的。RNA靶向基因治疗已经成为一种很有前途的方法，扩大了治疗ALS的可药物靶点。Drishti Discovery是一家先进治疗公司，使用专利的miRNA适配shRNA技术开发针对罕见疾病的疾病修饰基因疗法。我们正在应用这种RNA靶向技术来开发ALS的长期治疗方法。到目前为止，我们的数据表明，我们可以显著地沉默我们的感兴趣基因，并在急性ALS小鼠模型中拯救运动功能。在这个项目中，我们的目标是进一步发展该计划。我们将在一个独立的ALS小鼠模型中证实我们的候选药物的有效性，使我们的创新基因治疗产品更接近临床，为急需帮助的患者提供帮助。

Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron disease that causes death in patients within 3-5 years of diagnosis. Riluzole is the only approved drug in the UK that extends survival by 6 months. Increasing research in the pathophysiology of ALS has led to a deeper understanding of molecular mechanisms underlying the disease progression. Recently several exciting targets have been identified. Many of these targets are not druggable using the conventional small molecule and monoclonal antibody-based approach. RNA targeting gene therapy has emerged as a promising modality, extending druggable targets for the treatment of ALS.Drishti Discoveries is an Advanced Therapy company developing disease-modifying gene therapy for rare diseases using a proprietary miRNA-adapted shRNA technology. We are applying this RNA-targeting technology to develop a long-term treatment for ALS. Our data so far show we can significantly silence our gene of interest and rescue motor functions in an acute ALS mouse model.In this project, we aim to further progress the programme. We will confirm the efficacy of our candidates in an independent ALS mouse model to bring our innovative gene therapy product one step closer to the clinic for patients in urgent need.