Clotilde Lagier-Tourenne,
Assistant Professor of Neurology,
Massachusetts General Hospital and Harvard Medical School
Clotilde Lagier-Tourenne is Assistant Professor of Neurology at the Massachusetts General Hospital and Harvard Medical School, and Associate Member of the Broad Institute of MIT and Harvard University. She was trained as a Medical Geneticist in Strasbourg where her research focused on the identification of new genetic causes of neurological disorders. During her postdoctoral training at the University of California San Diego, she applied approaches in genomics to explore the molecular mechanisms that drive neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Her recent efforts have focused on understanding disease mechanisms and developing therapeutic strategies for ALS and FTD linked to C9ORF72 expansion. With her colleagues, she has provided evidence supporting the therapeutic potential of Antisense Oligonucleotides (ASOs) targeting C9ORF72 expansion. She received the Alphonse Laveran Prize, the Milton-Safenowitz Postdoctoral Fellowship from the Amyotrophic Lateral Sclerosis Association, the Muscular Dystrophy Association Career development Award, the Frick Foundation 2013 Award (conjointly with Dr. Luc Dupuis), and the 6th International Medicine Paulo Gontijo Award.
Using RNA Signatures For Therapeutic Development in Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia
Tuesday, 14 November 2017 at 09:00
Add to Calendar ▼2017-11-14 09:00:002017-11-14 10:00:00Europe/LondonUsing RNA Signatures For Therapeutic Development in Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal DementiaThe RNA Summit: Research, Diagnostics and Therapeutics in Boston, USABoston, USASELECTBIOenquiries@selectbiosciences.com
Expanded GGGGCC repeats in a non-coding region of the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Several pathogenic mechanisms have been proposed including loss of function from reduced expression of C9ORF72 and/or toxicity derived from the expansion-containing RNAs. Accumulation of nuclear RNA foci and cytoplasmic dipeptide repeat proteins (DPRs) translated from the repeat-containing RNAs are pathological hallmarks of disease in patient cells and mice expressing C9ORF72 RNAs with up to 450 repeats. Indeed, hexanucleotide expansions caused age-, repeat length- and expression level-dependent accumulation of RNA foci and DPRs, accompanied by loss of hippocampal neurons, increased anxiety, and impaired cognitive function in transgenic mice. The presence of pathological hallmarks of C9ORF72 disease and behavioral abnormalities establishes this mouse model as an essential tool to develop novel therapeutic approaches, including RNA-targeting antisense oligonucleotides and immunotherapies for patients with ALS/FTD. Antisense oligonucleotides (ASOs) were identified which reduce GGGGCC-containing nuclear foci without altering overall C9ORF72 RNA levels in patient cells. By contrast, siRNAs failed to reduce nuclear RNA foci despite marked reduction in overall C9ORF72 RNAs. In mice, single dose intracerebroventricular injection of ASOs that target repeat-containing RNAs produced sustained reductions in RNA foci and dipeptide-repeat proteins, and ameliorated behavioral deficits. These findings establish ASO-mediated degradation of repeat-containing RNAs as a significant therapeutic approach for ALS/FTD linked to C9ORF72 expansions.
Add to Calendar ▼2017-11-13 00:00:002017-11-14 00:00:00Europe/LondonThe RNA Summit: Research, Diagnostics and TherapeuticsThe RNA Summit: Research, Diagnostics and Therapeutics in Boston, USABoston, USASELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2017-11-14 09:00:002017-11-14 10:00:00Europe/LondonUsing RNA Signatures For Therapeutic Development in Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal DementiaThe RNA Summit: Research, Diagnostics and Therapeutics in Boston, USABoston, USASELECTBIOenquiries@selectbiosciences.com
