Therapeutic reduction of ataxin 2 extends lifespan and rescues pathological features of ALS in TDP-43 transgenic mice

old_uid12003
titleTherapeutic reduction of ataxin 2 extends lifespan and rescues pathological features of ALS in TDP-43 transgenic mice
start_date2016/09/05
schedule11h-12h
onlineno
detailsConférence de l'ICM. Invité par Edor Kabashi et Séverine Boillée
summaryAmyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease characterized by motor neuron loss, leading to paralysis and death 2-5 years following disease onset. Nearly all ALS patients contain aggregates of the RNA-binding protein TDP-43 in the brain and spinal cord and rare mutations in the gene encoding TDP-43 can cause ALS. There are no effective TDP-43-directed therapies for ALS or related TDP- 43 proteinopathies, such as frontotemporal dementia (FTD). Antisense oligonucleotides (ASOs) and RNA interference approaches are emerging as attractive therapeutic strategies in neurological diseases. Indeed, treating a rodent model of inherited ALS (caused by a mutation in SOD1) with ASOs to SOD1 significantly slowed disease progression. But since SOD1 mutations account for only ~2-5% of ALS cases, additional therapeutic strategies are needed. Silencing TDP-43 itself is probably not warranted given its critical normal cellular functions. Here we present an unexpectedly powerful alternative therapeutic strategy for ALS, by targeting ataxin 2.
responsiblesOliviero