Paul George, MD, PhD, Stanford University, Science Chair for AAN I'm Paul George. I'm the science chair for the American Academy of Neurology, and I'm based at Stanford University as a professor there. I think it's always a very vibrant conference with the whole field of neurology represented. I think some of the exciting things this year is that there's a lot more treatment abstracts and studies that have been submitted. I think we're shifting to this era in neurology where we have a lot of tools to help treat diseases.One of the ones at the plenary on the GLP-1 receptor agonists was very interesting. Those obviously have gotten a lot of acclaim for use in diabetes and weight loss, but there's developing evidence that they could be useful for cognitive disorders and other parts of neurologic disease.I think even over the last few years there's been some really great studies developing new biomarkers for Alzheimer's disease, Parkinson's disease. And it seems that that research is continuing to move forward. How can we diagnose these diseases even before maybe there's clinical signs of the disease.I think the other area that's been exciting is we, you know, as neurologists, we're a little limited once injury has been done to kind of restore brain function. And so, there's even the last couple years, there has been movement on neuromodulation. and using vagal nerve stimulation or other electrical stimulation to try to enhance recovery of the brain. And so, I think there's a lot of exciting research in that area, too, that we'll continue to see maybe a signal in neuromodulation to help with improvement of patient recovery.Tolebrutinib in Nonrelapsing Secondary Progressive Multiple SclerosisRobert J. Fox, M.D., Amit Bar‑Or, M.D., Anthony Traboulsee, M.D., Celia Oreja‑Guevara, M.D., Ph.D., Gavin Giovannoni, M.D., Ph.D., Patrick Vermersch, M.D., Ph.D., Sana Syed, M.D., M.P.H., Ye Li, Ph.D., Wendy S. Vargas, M.D., Timothy J. Turner, Ph.D., Erik Wallstroem, M.D., Ph.D. and Daniel S. Reich, M.D., Ph.D.Robert Fox, MD, Mellen Center for Multiple Sclerosis, Cleveland ClinicI am Dr. Robert Fox, a staff neurologist at the Mellen Center for Multiple Sclerosis. And I served as chair of the steering committee of the Hercules phase three clinical trial.The Hercules trial evaluated tolebrutinib in non-relapsing secondary progressive MS.Tolebrutinib is an orally, taken by mouth, administered BTK inhibitor. And importantly, it can penetrate into the brain at relevant concentrations that are thought to be helpful in fighting inflammation within the brain.In that trial, patients were enrolled from around the world and were randomized to receive either tolebrutinib once a day or a matching placebo, and then they were followed over several years.The primary outcome was progression of disability that was sustained for six months or more.Additional outcomes included other disability measures and MRI measures, and of course safety.Over 1,100 patients from around the world were randomized into the trial, and about 77% of them in each of the treatment groups completed the end of the trial.Those enrolled were typical of non-relapsing secondary progressive MS patients. They average about 49 years, and almost two thirds were women, and a median of over seven years since the last clinical relapse.The primary outcome, the top line outcome was met in that there was a 31% slowing of disability as measured by the six-month confirmed disability progression measure.Importantly, safety, there were some notable safety observations. The proportion of patients with serious side effects that emerge after starting treatment were a bit higher in those receiving tolebrutinib, about 15%, versus placebo, a little bit over 10%.The rates of some infections was a little higher with tolebrutinib too, including COVID-19 infection, nasopharyngitis, and also influenza.Importantly, the rate of liver irritation as measured by liver enzymes in the blood, the proportion of patients with that was increased in tolebrutinib compared to placebo. And about 0.5% or about one in 200 patients who received tolebrutinib had a very high elevation in liver enzymes, more than 20 times the upper limit of normal.One of those patients unfortunately progressed to liver failure and died following a liver transplant which emphasizes the seriousness of that safety issue.Now, all of those cases with liver enzymes above that 20 times upper limit normal cutoff were observed in the first three months of treatment and that's important because it provides us a very focused target area for close monitoring.So, in summary, the trial found that treatment with tolebrutinib slows progression of disability in non-relapsing secondary progressive MS, which is really exciting because this is the very first time we've identified a treatment that is effective for this form of MS. Now, there are safety concerns, particularly potential liver injury, and that will require careful counseling of patients who may consider this therapy and close monitoring, of course. But finally, I think a bright day has come for the have-nots with secondary progressive MS because we have finally found a treatment that may be helpful for them. .Sign up for our weekly HealthDay newsletter