Updated on
What did the project achieve?
“We have successfully identified a shortlist of promising compounds that could serve as starting points for developing a potential drug treatment for children with KCNT1-related epilepsies,” says Dr Jonathan Lippiat of the University of Leeds. “This research could ultimately lead to a safe and effective new medicine to help control seizures and prevent brain damage, offering hope to children and families affected by these rare and devastating conditions. We are now seeking funding and partnerships to take this further.”
Faults in the KCNT1 gene, which contains the instructions for making the KCNT1 protein, can cause severe neurological conditions. A child with KCNT1-related epilepsy will typically experience severe seizures beginning very early in life, often accompanied by delayed development, learning difficulties, behavioural or movement problems. Currently, there are no treatments available that adequately control seizures or improve other problems in these children.
This research aimed to identify promising drug candidates for developing an effective new medicine for children with KCNT1-related epilepsies. The team used a combination of computer and laboratory-based approaches to screen millions of chemical compounds and predict which ones are likely to block the activity of the KCNT1 protein.
“During this project, we obtained approximately 120 compounds and tested them in the laboratory,” says Dr Lippiat. “We found that around one-third of these compounds reduced the activity of the KCNT1 protein. By comparing their structures, we identified key features important for blocking KCNT1 protein activity, enabling us to create even more effective compounds.”
The team then conducted further experiments to assess potential toxic or unwanted effects that could prevent these compounds from becoming safe and effective drug treatments.
“This project has provided a springboard for our efforts to find a treatment for KCNT1-related epilepsies,” says Dr Lippiat. “It has motivated our research team and enabled us to demonstrate the suitability and benefits of our combined approach to drug discovery for rare diseases.”
This research was completed on
Faults in a gene called KCNT1 can cause severe neurological conditions in children, known as KCNT1-related epilepsies. Affected children often experience repeated seizures very early in life and many will also have delayed development, learning difficulties, behavioural or movement problems. Sadly, many will lose their lives before adulthood. Dr Jonathan Lippiat of the University of Leeds is aiming to identify chemical compounds that could form the basis of an effective new treatment for KCNT1-related epilepsies. In the longer term, developing a new drug that can control seizures and prevent brain damage could help transform the lives of children and families affected by these devastating conditions.
How are children’s lives affected now?
A child with a KCNT1-related epilepsy will usually experience severe seizures that begin in the first days or months of life. Some children will have repeated seizures every day, and many will have delayed development or other neurological problems.
“A child will typically start missing their developmental milestones in infancy or early childhood – and some will never learn to walk or talk,” says Dr Lippiat.
The KCNT1 gene provides the instructions for making a protein that plays a key role in the ability of nerve cells in the brain to generate and transmit electrical signals. Children with KCNT1-related epilepsies have faults in this gene that make this protein overactive. In turn, this leads to abnormal electrical activity in nerve cells – causing seizures.
“Currently there are no treatments that can adequately control seizures or improve other problems experienced by these children,” says Dr Lippiat. “Effective new treatments are desperately needed that can help to improve and extend their lives.”
How could this research help?
“Our goal is to identify promising drug candidates that could be developed into an effective new medicine for children with KCNT1-related epilepsies,” says Dr Lippiat.
The researchers previously used computer-based approaches to screen millions of different chemical compounds, narrowing down a shortlist that could have the ability to block the activity of the KCNT1 protein.
“We will now carry out laboratory tests to find out which of these chemicals might also have the right properties to be developed into a new medicine,” says Dr Lippiat.
By combining the results from their laboratory experiments and computer-based approaches, they hope to identify a range of potential drug candidates for development.
Developing a safe and effective new treatment that can help control seizures and prevent damage to children’s brains would greatly improve the quality of life for affected children and hopefully allow many more to reach adulthood.
Research table
Project details
| Project Leader | Dr Jonathan D Lippiat, PhD |
| Location | School of Biomedical Sciences, University of Leeds |
| Project Team |
Dr Stephan P Muench, PhD
Dr Katie J Simmons, PhD |
| Other Locations | Department of Discovery and Translational Science, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds |
| Grant Awarded | |
| Grant Amount | £144,250 |
| Start Date | |
| End Date | |
| Duration | 24 months |
| Grant Code (GN number) | GN2865 |
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