Patrick Aebischer | EPFL Graph Search

Patrick Aebischer a achevé une formation en Médecine (1980) et en Neurosciences (1983) aux Universités de Genève et de Fribourg en Suisse.

De 1984 à 1992, Patrick Aebischer a travaillé à Brown University (USA) au sein du Département des Neurosciences et au Département des Biomatériaux et des Organes Artificiels en tant que Professeur assistant, puis Professeur associé.

En 1992, Patrick Aebischer a été nommé Professeur de la Division Autonome de Recherche Chirurgicale et du Centre de Thérapie Génique (DARC) au Centre Hospitalier Universitaire Vaudois (CHUV) à Lausanne.

En 1999, Le Conseil Fédéral a nommé Patrick Aebischer en tant que Président de l'Ecole Polytechnique Fédérale de Lausanne (EPFL). Il a pris ses fonctions à la Présidence de lEPFL en mars 2000, position qu'il a occupée jusqu'au 31 décembre 2016.

Patrick Aebischer est membre de maintes sociétés professionnelles, tant en Europe quaux Etats-Unis.

Patrick Aebischer a fondé trois start-up de biotechnologies. Il siège au conseil d'administration de Lonza, de Logitech et de Nestlé. Il préside également l'advisory board du Novartis Venture Fund. Patrick Aebischer est membre du conseil de fondation du Festival de Jazz de Montreux, du Festival de Verbier et de la Fondation Jacobs.

Les recherches quil poursuit actuellement dans son laboratoire se concentrent sur le développement d'approches de thérapie cellulaire et de transfert génique pour le traitement des maladies neurodégénératives.

Astrocyte-targeting RNA interference against mutated superoxide dismutase 1 induces motoneuron plasticity and protects fast-fatigable motor units in a mouse model of amyotrophic lateral sclerosis

Patrick Aebischer, Nathalie Marie Géraldine Bernard, Cylia Cloé Rochat, Bernard Schneider

In amyotrophic lateral sclerosis (ALS) caused by SOD1 gene mutations, both cell-autonomous and noncell-autonomous mechanisms lead to the selective degeneration of motoneurons (MN). Here, we evaluate the therapeutic potential of gene therapy targeting mutated SOD1 in mature astrocytes using mice expressing the mutated SOD1(G93A) protein. An AAV-gfaABC(1)D vector encoding an artificial microRNA is used to deliver RNA interference against mutated SOD1 selectively in astrocytes. The treatment leads to the progressive rescue of neuromuscular junction occupancy, to the recovery of the compound muscle action potential in the gastrocnemius muscle, and significantly improves neuromuscular function. In the spinal cord, gene therapy targeting astrocytes protects a small pool of the most vulnerable fast-fatigable MN until disease end stage. In the gastrocnemius muscle of the treated SOD1(G93A) mice, the fast-twitch type IIB muscle fibers are preserved from atrophy. Axon collateral sprouting is observed together with muscle fiber type grouping indicative of denervation/reinnervation events. The transcriptome profiling of spinal cord MN shows changes in the expression levels of factors regulating the dynamics of microtubules. Gene therapy delivering RNA interference against mutated SOD1 in astrocytes protects fast-fatigable motor units and thereby improves neuromuscular function in ALS mice.

WILEY2022

Evolution of the neurochemical profiles in the G93A-SOD1 mouse model of amyotrophic lateral sclerosis

Patrick Aebischer, Elisabeth Anne Dirren, Rolf Gruetter, Hongxia Lei, Carole Poitry-Yamate, Bernard Schneider

In vivo (1)H magnetic resonance spectroscopy ((1)H-MRS) investigations of amyotrophic lateral sclerosis (ALS) mouse brain may provide neurochemical profiles and alterations in association with ALS disease progression. We aimed to longitudinally follow neurochemical evolutions of striatum, brainstem and motor cortex of mice transgenic for G93A mutant human superoxide dismutase type-1 (G93A-SOD1), an ALS model. Region-specific neurochemical alterations were detected in asymptomatic G93A-SOD1 mice, particularly in lactate (-19%) and glutamate (+8%) of brainstem, along with gamma-amino-butyric acid (-30%), N-acetyl-aspartate (-5%) and ascorbate (+51%) of motor cortex. With disease progression towards the end-stage, increased numbers of metabolic changes of G93A-SOD1 mice were observed (e.g. glutamine levels increased in the brainstem (>+66%) and motor cortex (>+54%)). Through ALS disease progression, an overall increase of glutamine/glutamate in G93A-SOD1 mice was observed in the striatum ( p < 0.01) and even more so in two motor neuron enriched regions, the brainstem and motor cortex ( p < 0.0001). These (1)H-MRS data underscore a pattern of neurochemical alterations that are specific to brain regions and to disease stages of the G93A-SOD1 mouse model. These neurochemical changes may contribute to early diagnosis and disease monitoring in ALS patients.

2019

The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans

Patrick Aebischer, Pénélope Andreux, Johan Auwerx, Frederic Burdet, Dongryeol Ryu, Anurag Singh

Urolithin A (UA) is a natural dietary, microflora-derived metabolite shown to stimulate mitophagy and improve muscle health in old animals and in preclinical models of aging(1). Here, we report the results of a first-in-human clinical trial in which we administered UA, either as a single dose or as multiple doses over a 4-week period, to healthy, sedentary elderly individuals. We show that UA has a favourable safety profile (primary outcome). UA was bioavailable in plasma at all doses tested, and 4 weeks of treatment with UA at doses of 500 mg and 1,000 mg modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression in elderly individuals (secondary outcomes). These observed effects on mitochondrial biomarkers show that UA induces a molecular signature of improved mitochondrial and cellular health following regular oral consumption in humans.

NATURE PUBLISHING GROUP2019