My Name’5 Doddie Foundation invests in pioneering MND gene therapy research

27 June 2023

• Dr Andrea Perera, King’s College London, is the lead investigator on a research project that could result in both a new drug for motor neuron disease (MND) and a pioneering drug delivery technique
• The drug works by reducing levels of the toxic protein TDP-43, a hall-mark of MND in over 90% of people living with the disease
• A new delivery technique could increase the amount of drug that reaches the motor neurons, increasing it’s effectiveness

My Name’5 Doddie Foundation recently awarded Dr Perera, a neurosurgical trainee at King’s College London, up to £250,000 for her research into the delivery of a new drug to treat MND. Dr Perera and co-investigators Professor Chris Shaw, Professor Keyoumars Ashkan and Dr Olivier Brock will use their novel gene therapy targeted at the protein ataxin-2 to optimise the ‘subpial’ injection technique, first developed in the United States.

Gene therapy development

A common characteristic of MND is the toxic build-up of a protein called ‘TDP-43’ in the motor neurons. Clumps of TDP-43 are known to drive pathology of MND and are a major target for the development of new drugs. Another protein, called ataxin-2, has been shown to play an important role in the build-up of TDP-43.

Dr Perera’s project will investigate the potential of a new gene therapy drug, to reduce the level of ataxin-2 in motor neurons, therefore reducing the amount of toxic TDP-43 build-up. This pathology affects over 90% of people living with MND, so a drug that targets this pathway specifically could be beneficial to the majority of people diagnosed with the disease and would profoundly change the treatment landscape in the future.

A new approach to drug delivery

Motor neurons reside in the brain and spinal cord, but delivering drugs to these highly specialised organs is complex and often unsuccessful; they are surrounded by a series of specialised membranes, collectively known as the blood brain barrier (BBB). In most cases, the BBB is hugely beneficial to humans; it keeps pathogens and toxic substances away, but it also blocks the access of many drugs. A new technique, called subpial injection, that involves the delivery of drugs by injection directly into the space beneath these membranes, dramatically increases the amount of drug that can reach the motor neurons in the brain and spinal cord in animal models of MND. Dr Perera will optimise this technique, testing the distribution of the new gene therapy drug against ataxin-2, in animal models of the disease.

Gaining evidence that this delivery technique can be used to deliver high quantities of the drug to the motor neurons, and that ataxin-2 can be reduced as a result, will be critical to laying the groundwork for clinical trials in people living with MND in the future. What’s more, if the technique is successful, it could also be used to deliver other drugs already available, potentially increasing their effectiveness, as well as new drugs that are yet to be developed.

Dr Perera said, “We hope that by combining novel neurosurgical techniques with cutting edge gene therapies from Professor Shaw’s laboratory that we can offer new research avenues and ultimately treatment options for this devastating disease. It is also my goal to interest a new generation of neurosurgeons in drug delivery research in MND which will become more vital as treatment targets improve”.

Jessica Lee, Director of Research at the Foundation said, “We are committed to funding research that will accelerate the development of new treatments for MND and we are excited to see this project, which does exactly that, is now underway. We would like to thank our independent peer reviewers who reviewed this application and provided valuable feedback to ensure the project would have the most impact for people living with MND. Funding this work is only possible with the incredible fundraising efforts of our supporters.”