The first two epilepsy patients to receive an experimental stem cell therapy experienced an almost complete reduction in seizures a year after treatment, early trial results show.
The therapy involves a single brain injection of lab-grown neurons that are designed to dampen electrical activity with the aim of stopping seizures. It is too early to confirm whether the approach is effective but the initial results, presented at the International Society for Stem Cell Research’s annual meeting in Boston last week, are viewed as extremely encouraging.
“Although our clinical investigation is ongoing in additional patients, it is gratifying to witness the first two patients achieving seizure relief without additional cognitive impairment to date,” said Cory Nicholas, the CEO of Neurona Therapeutics, the San Francisco-based biotech company that developed the therapy. “We are hopeful that these improvements will continue in the ongoing trial.”
Epilepsy is caused when the balance in the brain between excitatory neurons, which fire signals, and inhibitory neurons, which dampen down this activity, goes awry. The condition affects more than 600,000 people living in the UK.
For roughly 30% of people, seizures cannot be controlled with medication. In some cases, surgery can be performed if seizures are centred on a specific area of the brain. However, removing brain tissue carries the risk of irreversible cognitive deficits, meaning there is a huge need for alternative, non-destructive treatments.
In the US trial, both patients were severely affected by epilepsy and drug treatments had not worked. The first patient, treated at SUNY Upstate Medical University, had suffered from epilepsy for seven years and in the six months before the trial was having an average of 32 seizures a month. The second patient, treated at the Oregon Health & Science University, had a nine-year history of seizures and had about 14 seizures a month in the six months before receiving the cell injection.
Both were candidates for surgical treatment before entering the trial. “Instead, they courageously chose to be first to receive NRTX-1001 cell therapy,” Nicholas said.
The therapy involves injecting a high concentration dose of inhibitory neurons into the focal point of the patient’s seizures. The cells are grown in the laboratory from human embryonic stem cells. Previous research in animals found that the injected neurons were able to integrate with existing brain circuits and produce lasting suppression of seizures.
After the cell therapy, the first patient had a more than 95% reduction in monthly seizures and did not have any seizures beyond the seventh month of the follow-up period. The patient also had improved memory scores on cognitive tests. The second patient had a more than 90% reduction in monthly seizures.
“Both patients entered the clinical trial with significant seizure activity, impaired cognition and suboptimal quality of life,” Nicholas said.
Prof Peter Oliver, the head of biology at the Medical Research Council’s Nucleic Acids Therapy Accelerator laboratory in Oxford, who was not involved in the research, said: “This new, early clinical trial data suggests that delivering these inhibitory neurons can significantly reduce the number of seizures in two patients with focal epilepsy. This type of cell therapy has significant potential as an alternative to surgical interventions in this type of epilepsy and for those that do not respond to medication.”
Maxine Smeaton, the chief executive of Epilepsy Research UK, said: “For the 30% of people with epilepsy whose seizures are not controlled, we urgently need new and innovative treatments. Developments in personalised medicines such as stem cell and gene therapy research offer much hope. However, research into epilepsy has been chronically underfunded. Despite being one of the most common, serious neurological conditions, just 0.3% of the £4.8bn government funding spent on health-related research in 2018 was invested in epilepsy.”
