Martha McLaughlin, UCL Institute of Neurology

Restoring muscle function using optogenetics (PhD studentship)

Martha McLaughlin was awarded a place on the prestigious four-year Clinical Neurosciences PhD programme at UCL Institute of Neurology in 2016, funded by Brain Research UK. 

The first year of the Clinical Neurosciences PhD is a training year, in which students attend some specialised courses and do three short research projects in different labs, helping them to gain experience and build expertise across different areas of neuroscience. They then choose a supervisor and develop a full research project for the subsequent three years.

Having completed her training year, Martha was keen to work with Professor Linda Greensmith and Dr Barney Bryson, with whom she collaborated during her first rotation. Their work, in the Sobell Department of Motor Neuroscience and Movement Disorders, focuses on disorders that affect the neuromuscular system, in particular motor neurone disease.

Martha is taking forward the development of optogenetics, a technique that holds promise for the restoration of muscle function in patients with degenerative diseases such as motor neurone disease, as well as those with paralysis caused by traumatic injury.

About motor neurone disease

Motor neurone disease (MND) is a fatal, rapidly progressing neurological disease. It attacks the nerves that control movement (motor neurones) so that muscles no longer work.

This initially leads to weakness and wasting and then, eventually, severe paralysis and breathing difficulties.

More than 2,000 people are diagnosed with MND every year in the UK. There is no cure; a third of patients die within a year and more than half within two years of diagnosis.

Read more: Motor neurone disease                                   

Restoring muscle function using optogenetics

Our brains control movement by sending signals via specialised cells called neurones, down through the spinal cord and along nerves to stimulate muscle contraction. Damage to any part of this pathway – whether by disease or injury - can cause loss of motor function, resulting in muscle paralysis.

Despite intensive research, there are no effective therapies to promote spontaneous regeneration of damaged or diseased neurones in the brain and spinal cord in order to restore motor function.

An alternative approach is to introduce new neurones to support or replace the damaged neurones in the spinal cord. The new neurones can be generated from stem cells, which can be induced to grow into any cell type.

However, transplantation of these neurones into the spinal cord presents a number of challenges. One challenge lies in the fact that transplanted motor neurones would need to grow out long projections (axons) along nerves towards the correct muscles, which may be as much as a metre away from the spinal cord.

One way to overcome this is to transplant the neurones outside of the spinal cord, so that they will have a shorter length to grow to reach their target muscles. But because they are outside the spinal cord, the neurones then need to be artificially stimulated in order to activate muscle contractions. Previous studies have used electrical stimulation but this has a number of disadvantages including pain caused by the activation of sensory neurones.

Prof Greensmith and Dr Bryson have developed an alternative approach that exploits a new technique called optogenetics. This involves genetic modification of motor neurones so that they can be stimulated by light rather than electricity. This does not affect the sensory neurones and will not, therefore, cause pain.

Martha will work on the continued development of this technique to optimise the ability to restore muscle function.

Impact

This work should provide answers to important questions about how motor neurones mature and form connections with muscle, questions that are important in furthering our knowledge of motor neurone function in both health and disease.

Martha’s results will help to optimise the group’s optogenetic neural replacement strategy, working towards the development of neural replacement as a potential therapy for the restoration of motor function after disease or injury.