March 24, 2025 at 12:30 pm US EST
We developed personalized splice-modulating ASOs targeting a deep intronic variant in PEX1 in a 2 year old male with Zellweger Spectrum Disorder, a progressive and debilitating peroxisomal disorder for which there is currently no disease modifying therapy available. Lead candidate ASOs rescued mis-splicing in a dose dependent fashion, restored wild type transcript close to carrier levels, increased PEX1 protein, and restored peroxisomal number and function. Unfortunately the index patient passed away before an N=1 trial could be initiated; nonetheless these efforts provide a pilot template for potential future personalized ASO therapies for PEX1-related Zellweger Spectrum Disorder.
Dr. Robert Thompson: I completed my pediatrics residency in the Boston Combined Residency Program at Boston Children's Hospital & Boston Medical Center and I am currently a genetics & metabolism fellow in the Harvard Medical School Genetics Training Program as well as a research fellow in the MGB Neurogenetics and Gene Therapy Fellowship. I plan to practice biochemical genetics and do translational research in the gene-targeted therapy space with the goal of helping to bring these therapies from bench to bedside for patients with inborn errors of metabolism and other genetic disease.
Dr. Claudia Lentucci: I received my PhD in Biotechnology and Genomics at the University of Siena and then completed my postdoc at BU and Dana Farber. I am currently a Senior Staff Scientist at Boston Children’s Hospital where I work in clinical research focusing on IND enabling studies for neurodegenerative rare diseases and n of 1 ASO programs. Â
Dr. Didem Demirbas: I am a broadly trained molecular biologist and a board-certified clinical biochemical geneticist with a research focus on neurodevelopmental disorders and inborn errors of metabolism. I received my PhD in Biology from Boston College and trained in biochemical genetics at the Harvard Medical School Genetics Training Program. I continue my postdoctoral work in Dr. Timothy Yu’s laboratory at Boston Children’s Hospital. I am developing neuronal differentiation and cerebral organoid models to study neurological complications associated with genetic disorders and work on antisense oligonucleotide-based N of 1 studies.