Antibodies are the molecular soldiers in our immune system’s army, fighting to protect us from, yes, you guessed it, VIRUSES, as well as other bugs and threats that may cause disease. However, sometimes these antibodies get distracted or confused (for example, by viruses or a tumour) and instead of protecting us and our vital organs, they start attacking them, and become autoantibodies. When these autoantibodies target proteins within the brain, this can result in an autoimmune neurological condition known as autoimmune encephalitis. Affected patients, adults or children, will display changes in behaviour, seizures and abnormal movements among other symptoms. The seizures mostly occur during the condition, but some patients can be left with ongoing seizures and develop an autoimmune associated epilepsy. We also know that although most patients make a good recovery, sufferers of autoimmune encephalitis and associated epilepsy can be left with longstanding cognitive problems. This has recently been identified as a particular problem in children. My research has been focused on trying to understand how these antibodies cause seizures and whether there are ways of improving treatments so that we can prevent any long-term problems.
The autoantibodies that I have focused on in my Epilepsy Research UK-funded project target a protein in the brain called the NMDA receptor (NMDAR), which is crucial to making brain cells communicate with one another – known as ‘firing’. Using a wide range of laboratory methods, we have managed to make an experimental seizure model caused by the NMDAR antibodies and used this to understand why seizures occur when the NMDAR brain protein is disrupted. Turns out it’s not as simple as we thought…
The good news is we managed to partially reverse the change in neuron firing pattern that happens when a seizure occurs caused by NMDAR antibodies, with a treatment targeting the NMDAR brain protein. We also showed this treatment had the same effect on human brain tissue (kindly donated by patients undergoing epilepsy surgery, as part of another project funded by Epilepsy Research UK!) which is the first step towards translating this treatment from lab bench to bedside. We hope this research will lead to additional targeted treatments for patients and allow refinement of immune-targeting drug therapy and minimizing of side effects.
It continues to be an absolute privilege to be able to conduct research which could be directly applicable to the patients I see in the clinic. I am frequently humbled by how eager patients are to participate in research, even when the findings may have no direct impact on them or their loved ones; their motivation – a selfless act of compassion to help others. Similarly, I am also amazed and excited by other researchers and clinicians, always keen to collaborate in these same research studies, even when competing pressures are high (COVID-19!). I am very thankful to Epilepsy Research UK and their incredible supporters for their continued efforts to drive research into epilepsy and keep it in the spotlight. With one new patient diagnosed with epilepsy every minute within the UK and Europe, there is an urgent clinical need to understand seizure-inducing pathways in brain networks, particularly for those patients that will not be helped with standard treatments.
-Dr Sukhvir Wright