Professor Linda Greensmith, UCL Institute of Neurology

Professor Linda Greensmith heads the Graeme Watts Laboratory at UCL Institute of Neurology in London.

She founded the Lab in 1999, supported by funds left to Brain Research UK by the family of Graeme Watts, who died of motor neurone disease (MND) at the neighbouring National Hospital for Neurology and Neurosurgery. Graeme’s family left a bequest in his name to fund research to improve the basic understanding of MND and to develop therapeutic strategies.

No-one at the Institute was really working on MND at that time and Linda was recruited to set up a lab to take forward research into this devastating disease.

Nearly twenty years on, she has had remarkable success. The Graeme Watts Laboratory is at the forefront of research into MND, and drug compounds that started life there are now undergoing clinical trial. We continue to fund work there using funds from the endowment established in Graeme’s name.

About motor neurone disease

MND is a fatal, rapidly progressing neurological disease. It affects the muscles that control movement, robbing patients of their ability to walk, talk and eventually their ability to swallow and breathe.

It has no cure. It kills a third of patients within a year and more than half within two years of diagnosis.


Research in the Graeme Watts Laboratory

In 1999, with funding from the Graeme Watts Endowment, Linda Greensmith took on the challenge of setting up a new laboratory for research into motor neurone disease.

Since then, the lab has grown enormously, with a team of around 20 people working on MND and related diseases.

The lab has played a huge role in developing research capacity in MND. Linda has trained 26 PhD students and seven clinical fellows. The lab benefits from its close physical proximity to the National Hospital for Neurology and Neurosurgery, and enjoys good collaborative links with the clinicians there, unusual for a basic science lab but enormously important in ensuring that the work has translational relevance.

Research success

In some of the early research to take place in the lab, Linda demonstrated that one of the key features of MND is a clumping of proteins in motor neurones. This clumping also happens in other neurodegenerative diseases, but in different cells.

The team has subsequently been targeting this process as a possible therapeutic strategy to establish, firstly, whether they can find a way to prevent the clumping and, secondly, whether this halts disease progression.

They developed a drug that they showed could work on cells in a dish (in vitro) and also in animals (in vivo). The drug (Arimoclomol) has now undergone early phase trials in the US; results reported in December 2016 showed that the drug is safe and well-tolerated in patients and appeared to show a slowing of functional decline. Accordingly, the drug is now progressing to a larger trial to establish its effectiveness in a larger group of people with MND.

Broader relevance

As a basic scientist, Linda is interested in the processes underlying disease, and the boundaries between different diseases are quite fluid. The protein mis-folding that takes place in motor neurones in patients with MND is also important for patients with other neurodegenerative diseases such as dementia and Parkinson’s disease. It just happens in different cells. So whilst the Graeme Watts Lab is set up to look at MND, the team’s work has relevance to many other diseases of the neuromuscular system, underscoring the huge importance of the cross-disciplinary working that is part of the Lab’s ethos.

Because of the group’s interest in the protein mis-folding process, they have looked at a muscle disease called inclusion body myositis (IBM) in which clumps of proteins clog up muscle cells. They tested the same drug in this disease and, again, it showed promise at every stage of lab testing. Early stage trials with IBM patients in the UK have now taken place, again with positive results, and the drug is now moving forward to phase III trial.

“There’s not many groups that get things through from working in cells to working in mice and then getting them into the clinic. That translation, hitting each part of the translational pipeline is really nice and is very rare.” Professor Linda Greensmith