MICA: M102, A Combined NRF2 and HSF1 Activator for the Treatment of Motor Neuron Disease

该项目的目的是完成药物开发的关键阶段，以便为一种有希望的治疗运动神经元疾病（MND）的新疗法进行临床试验。运动神经元疾病是一种快速进展的、致命的神经退行性疾病。在谢菲尔德大学，我们已经确定了一种名为M102的候选药物，它可以进入大脑和脊髓，激活一些生物途径，从而开启一系列基因的表达。这些基因在细胞中有许多作用，可以提高细胞在各种应激因素中生存的能力，这些应激因素已知在神经元死亡中起作用。这些压力因素包括自由基、炎症和蛋白质团块或聚集体。我们希望，通过针对神经元应激和死亡的多种不同原因，我们将增加这种药物在大范围患者和疾病过程的所有阶段起作用的可能性。我们已经在各种动物模型和MND患者的脑细胞（来自他们的皮肤细胞）中证明，我们可以减缓疾病进程并保护神经元免于死亡。下一阶段是按照公认的监管标准生产药物，并在动物身上测试可能的副作用——这是在进行人类研究之前的要求。这些研究将由专门从事这项工作的专业公司进行。另一项工作将在谢菲尔德进行，使我们能够使用生物信号来识别被称为生物标志物的精神病患者，他们最有可能从服用这种药物中受益。这些生物标记物增加了药物在大型临床研究中显示效果的机会。我们已经做了一些初步的研究，表明我们的计划可能会成功，但我们将分阶段进行这项工作，以减少与出现问题相关的风险。作为一所大学，我们不太可能让药物通过临床测试的所有阶段，所以我们有一个工业合作伙伴，Aclipse One，他们将分担项目的成本和风险，但随后将能够让药物通过临床开发阶段。

The aim of this project is to complete the key stages of drug development needed to enable a clinical trial for a promising new treatment for motor neuron disease (MND), a rapidly progressive, fatal neurodegenerative disorder. At the University of Sheffield we have identified a candidate drug called M102, which can get into the brain and spinal cord and activate a number of biological pathways which switch on the expression of a range of genes. These genes have a number of effects in cells which improve their ability to survive various stress factors which are known to play a role in the death of neurons. These stress factors include free radicals, inflammation and protein clumps or aggregates.We hope that by targeting multiple different causes of neuronal stress and death we will increase the probability that this drug will work in a wide range of patients and at all stages of the disease process. We have already shown in various animal models and in brain cells from patients with MND (derived from their skin cells) that we can slow down the disease process and protect neurons from death. The next stage is to manufacture the drug to accepted regulatory standards and test it for possible side effects in animals- a requirement before conducting studies in humans. These studies will be carried out by expert companies who specialise in this work. Another strand of work will be conducted at Sheffield to allow us to be able to identify using biological signals called biomarkers the MND patients who are most likely to benefit from taking the drug. These biomarkers increase the chance of the drug showing effects in large clinical studies.We have already done some preliminary studies to show that our plan is likely to be successful but we will conduct the work in stages to reduce the risks associated with problems arising. As a University it is unlikely that we would take the drug through all the stages of clinical testing and so we have an Industrial partner, Aclipse One, who will share the costs and the risks of the project but will then be able to take the drug through the clinical stages of development.