Molecular and Cellular Mechanisms of Motor Neuron Disease

The focus of research in  our laboratory is on elucidating the underlying molecular and cellular mechanisms of motor neuron disease and to identify molecular biomarkers that could assist with early diagnosis and prediction of the disease and its progression rate. 

Motor neuron diseases (MNDs) are a group of neurodegenerative disorders that selectively target motor neurons of the brain and/or spinal cord. They strike at all stages of life and carry a lifetime risk of 1 in 500 in women and 1 in 350 in men in the UK. Amyotrophic lateral sclerosis (ALS), the most common form of adult-onset MND, is a progressive disease that affects motor neurons in the brain and spinal cord, leading to weakness and wasting of muscles and consequently loss of muscle movement and strength. Most people with ALS die of respiratory failure within 2-5 years after appearance of the symptoms. ALS is mainly a sporadic disease, but mutations in several genes cause familial ALS and contribute to the development of sporadic form of the disease. 

Spinal muscular atrophy (SMA) is a genetic form of MND mainly affecting children. SMA is caused by a loss of spinal motor neurons. This leads to weakness and wasting (atrophy) of muscles used for movement. In severe cases of SMA muscles used for breathing and swallowing are also affected. There are several types of SMA distinguished by the pattern of inheritance, disease severity and features. Children with the most severe type of SMA rarely survive beyond 2 years of age as a result of sever breathing difficulties. Spinal muscular atrophy, lower extremity, dominant (SMA-LED) is a childhood form of SMA characterised by progressive weakness in the leg muscles. Children with SMA-LED exhibit abnormal gait with delayed motor milestones and difficulty in rising from a seated position. SMA-LED is frequently accompanied with cognitive impairment.