Impressions from the 2023 American Epilespsy Society Meeting

The American Epilepsy Society (AES) held its yearly conference in Orlando in early December. This conference brings together physicians, scientists, advocates, and pharma companies to discuss all things ‘epilepsy’ through talks, poster presentations, and symposia. This year’s conference continued a trend that has been growing over the past few meetings, an increased attention on genetic epilepsies like STXBP1. At this year’s meeting, there were more talks and posters on various rare epilepsy syndromes than ever before, including 13 posters discussing STXBP1. It is also apparent that genetic epilepsies have become a primary focus for drug development by pharma companies. This was underscored by an unexpected poster presented by the pharma company UCB, which presented preclinical data on a mouse model of STXBP1, a crucial step in the drug-development process.

The Foundation’s collaborators at Children’s Hospital of Philadelphia and Children’s Hospital of Colorado presented various posters on STXBP1. The CHOP team, headed by Ingo Helbig, presented 4 posters including Julie Xian’s excellent analysis of forecasting seizure activity in the STXBP1 population, which should help in the design of future clinical drug trials. Kim Thalwitzer presented data showing that seizures in the first year of life do not impact the risk of developing epileptic spasms in STXers. Katie Rose Sullivan examined how common variants in STXBP1 may be linked to specific movement problems. Peter Galer rounded out the CHOP group’s posters with his early findings analyzing EEGs; he identified specific EEG patterns in the STXBP1 population that were different than patterns observed in other genetic epilepsies. These patterns could eventually be an important biomarker for STXBP1.

The Colorado group, headed by Scott Demarest, presented 3 posters with important implications to our ongoing STARR natural history study. Andrea Miele showed that neuropsychological assessments performed in the clinic in kids with STXBP1 correlate well with caregiver reported outcomes. Katie Angione presented a poster on using a newly developed outcome measure, the Clinical Severity Assessment tool, in evaluating kids with DEEs. Megan Abbott presented her findings that cortical visual impairment is an underdiagnosed finding in DEEs, including STXBP1, where she has found the condition in about 60% of STXers.

The natural history or progression of STXBP1 was also examined in several other poster presentations. Encoded Therapeutics presented their findings in the ENGAGE Study describing the lived experience and journey through the healthcare system of STXBP1 families. This study is an important step towards a potential clinical trial of any future Encoded drug.  A group from the University of British Columbia reported a decline in adaptive function in 25 STXers in Canada followed over the past three years in a small natural history study. Sick Kids in Toronto discussed the effectiveness of vagal nerve stimulation on seizure burden in two out of four kids treated with surgery. Mathieu Milh's French group described EEG activity in Early Infantile Developmental and Epileptic Encephalopathies (EIDEE), finding differences in STXBP1 compared to other genetic causes. An Italian group retrospectively reviewed 160 patients with DEEs, including 12 with STXBP1, and showed progression of EEG changes and cognitive function over time, though these findings were for the entire cohort of 160 patients and not broken down per genetic cause.

In addition to meeting with and discussing the latest STXBP1 findings with scientists and researchers, the Foundation was able to connect with several of our pharma partners.  They are always impressed by how engaged our population is and were very impressed and enthusiastic about how far the STARR study has come in such a short period of time, and the work being done towards the development of biomarkers. The AES meeting is also an opportunity for us to connect with other patient advocacy groups through events like the Rare Epilepsy Network breakfast meeting and other social gatherings. There is a general agreement that an inflection point has been reached regarding the recognition and importance of the rare epilepsies in the medical and pharma communities, and that more research will be needed as we move toward more personalized medicine and gene therapy type approaches for the treatment of epilepsy and related conditions.