Dr. Laura Montier
Baylor College of Medicine, USA
Dr. Montier recently completed her doctoral dissertation on Dravet syndrome at the University of Houston under the mentorship of Dr. JokÅ«bas Å½iburkus. She is passionate about improving the lives of children diagnosed with this devastating disorder and is continuing her research in the field with Dr. Alica Goldman at Baylor College of Medicine in the Houston Medical Center. Her postdoctoral work involves examining the genetics of families of patients with Dravet-like epilepsy disorders. In addition to her dedication to epilepsy research, Dr. Montier seizes every opportunity to encourage the aspirations of students striving to become scientists or medical professionals. She has six years of teaching experience, and has mentored research projects for three undergraduate students. Dr. Montier is eager to pursue interdisciplinary approaches to the complex problems found in the field of epilepsy.
Statement of the Problem: More than 30% of patients diagnosed with Dravet syndrome (DS) suffer from intractable epilepsy that put them at high risk for premature death. About 20% of DS patients die from sudden unexplained death in epilepsy (SUDEP). In addition, all DS patients experience at least some degree of autistic-like impairments, and about 25% are diagnosed with full Autism Spectrum disorder (ASD). The goal of this study is to test the long-term effects of a novel pharmaceutical approach that targets excitation, instead of inhibition, in a DS mouse model.
Methodology: Mice were administered N6-cyclopentyladenosine (CPA), an A1R agonist, twice daily by i.p. injection during early development. Two regimens were tested: a short-course from P11-20 and a long-course from P11-30. The long-term effects on viability, behavioral comorbidities, and the astroglial environment were assessed for each regimen. Anxiety (open field), sociability (3-chamber), and long-term memory (contextual-fear conditioning) were quantified at 8, 9, and 10 weeks, respectively. Confocal microscopy was employed to image brains of adult mice that had been labeled with anti-GFAP immunofluorescent staining techniques. Three-dimensional assessment of the astroglial environment was carried out with FarSight image analysis software. Findings: A short-course with CPA improved viability, while a long-course showed initial protection, but continued treatment reinstated decline in survival. The short-course improved sociability, restored long-term memory, and blocked astrogliosis in adult mice.
Conclusion & Significance: Currently, no anti-epileptic drug (AED) effectively controls seizures for one third of DS patients, and these children can experience hundreds of seizures every day. The novel pharmaceutical therapy with A1R agonist CPA presented here protected against premature death and showed long-term improvements in comorbidities in a DS mouse model, making a case for exploring adenosine therapy during early development clinically.