Publications de Patrick Aebischer

Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults

Patrick Aebischer, Johan Auwerx, Pénélope Andreux

Targeting mitophagy to activate the recycling of faulty mitochondria during aging is a strategy to mitigate muscle decline. We present results from a randomized, placebo-controlled trial in middle-aged adults where we administer a postbiotic compound Uroli ...

2022

Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults A Randomized Clinical Trial

Patrick Aebischer

IMPORTANCE Aging is associated with a decline in mitochondrial function and reduced exercise capacity. Urolithin A is a natural gut microbiome-derived food metabolite that has been shown to stimulate mitophagy and improve muscle function in older animals a ...

AMER MEDICAL ASSOC2022

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

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 mutat ...

WILEY2022

Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population

Patrick Aebischer, Johan Auwerx, Pénélope Andreux, Davide D'Amico

Background Urolithin A (UA) is produced by gut microflora from foods rich in ellagitannins. UA has been shown to improve mitochondrial health preclinically and in humans. Not everyone has a microbiome capable of producing UA, making supplementation with UA ...

2021

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

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

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 neur ...

2019

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

Patrick Aebischer, Frederic Burdet, Johan Auwerx, Pénélope Andreux, 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 adm ...

NATURE PUBLISHING GROUP2019

Cas9/gRNAs Selective Targeting of the Beethoven Tmc-1 Mutant Allele for Treating Progressive Hearing Loss by AAV-Based Delivery

Patrick Aebischer, Bernard Schneider, Paola Andrea Solanes Vega

CELL PRESS2018

Cas9/gRNA selective targeting of the Beethoven tmc-1 mutant allele for treating progressive hearing loss by AAV-based delivery

Patrick Aebischer, Paola Andrea Solanes Vega

MARY ANN LIEBERT, INC2018

Parkin functionally interacts with PGC-1 proportional to to preserve mitochondria and protect dopaminergic neurons

Patrick Aebischer, Bernard Schneider, Graham Knott, Johan Auwerx, Darren Moore, Norman Lionel Moullan, Lu Zheng, Nathalie Marie Géraldine Bernard, Davide D'Amico

To understand the cause of Parkinson's disease (PD), it is important to determine the functional interactions between factors linked to the disease. Parkin is associated with autosomal recessive early-onset PD, and controls the transcription of PGC-1a, a m ...

Oxford University Press2017

A subcutaneous cellular implant for passive immunization against amyloid-beta reduces brain amyloid and tau pathologies

Patrick Aebischer, Bernard Schneider, Vanessa Laversenne, Aurélien Lathuilière, Marco Stampanoni

Passive immunization against toxic misfolded proteins could offer protection against neurodegenerative disease. LathuiliSre et al. report the development of a retrievable device to encapsulate cells secreting recombinant anti-amyloid-beta antibodies. When ...

Oxford Univ Press2016

Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents

Patrick Aebischer, Maria del Carmen Sandi Perez, Elena Katsyuba, Johan Auwerx, Damien Sébastien Huzard, Norman Lionel Moullan, Pénélope Andreux, Evan Graehl Williams, Dongryeol Ryu, Laurent Mouchiroud, Giuseppe Lo Sasso, Pooja Jha

The biological effects of urolithins remain poorly characterized, despite wide-spread human exposure via the dietary consumption of their metabolic precursors, the ellagitannins, which are found in the pomegranate fruit, as well as in nuts and berries. We ...

2016

Use of a Bicistronic Vector to Silence SOD1 in Motoneurons and Astrocytes for the Treatment of Familial Amyotrophic Lateral Sclerosis

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

Nature Publishing Group2016

Alpha-Synuclein as a Mediator in the Interplay between Aging and Parkinson's Disease

Patrick Aebischer, Bernard Schneider, Wojciech Janusz Bobela

Accumulation and misfolding of the alpha-synuclein protein are core mechanisms in the pathogenesis of Parkinson's disease. While the normal function of alpha-synuclein is mainly related to the control of vesicular neurotransmission, its pathogenic effects ...

Mdpi Ag2015

Perineuronal net digestion with chondroitinase restores memory in mice with tau pathology

Patrick Aebischer, Bernard Schneider

Alzheimer's disease is the most prevalent tauopathy and cause of dementia. We investigate the hypothesis that reactivation of plasticity can restore function in the presence of neuronal damage resulting from tauopathy. We investigated two models with tau h ...

2015

Channel-Mediated Lactate Release by K+-Stimulated Astrocytes

Patrick Aebischer, Sylvain Eric Lengacher, Pierre Magistretti, Bernard Schneider

Excitatory synaptic transmission is accompanied by a local surge in interstitial lactate that occurs despite adequate oxygen availability, a puzzling phenomenon termed aerobic glycolysis. In addition to its role as an energy substrate, recent studies have ...

Society for Neuroscience2015

SOD1 silencing in motoneurons or glia rescues neuromuscular function in ALS mice

Patrick Aebischer, Bernard Schneider, Cylia Cloé Rochat, Christopher Towne, Julianne Bobela, Elisabeth Anne Dirren

Objective: Amyotrophic lateral sclerosis is an incurable disorder mainly characterized by motoneuron degeneration. Mutations in the superoxide dismutase 1 (SOD1) gene account for 20% of familial forms of the disease. Mutant SOD1 exerts multiple pathogenic ...

Wiley-Blackwell2015

Tmc gene therapy restores auditory function in deaf mice

Patrick Aebischer, Bernard Schneider, Cylia Cloé Rochat

Genetic hearing loss accounts for up to 50% of prelingual deafness worldwide, yet there are no biologic treatments currently available. To investigate gene therapy as a potential biologic strategy for restoration of auditory function in patients with genet ...

American Association for the Advancement of Science2015

Intracerebroventricular Injection of Adeno-Associated Virus 6 and 9 Vectors for Cell Type-Specific Transgene Expression in the Spinal Cord

Patrick Aebischer, Bernard Schneider, Christopher Towne, Veronica Setola, Elisabeth Anne Dirren

In the context of motoneuron diseases, gene delivery as an experimental or therapeutic approach is hindered by the challenge to specifically target cell populations that are widely distributed along the spinal cord. Further complicating the task, transgene ...

Mary Ann Liebert2014

A high-capacity cell macroencapsulation system supporting the long-term survival of genetically engineered allogeneic cells

Patrick Aebischer, Matthias Lütolf, Bernard Schneider, Steffen Cosson, Aurélien Lathuilière

The rapid increase in the number of approved therapeutic proteins, including recombinant antibodies, for diseases necessitating chronic treatments raises the question of the overall costs imposed on healthcare systems. It is therefore important to investig ...

Elsevier2014

A Parkinson's disease gene regulatory network identifies the signaling protein RGS2 as a modulator of LRRK2 activity and neuronal toxicity

Patrick Aebischer, Liliane Glauser, Bernard Schneider, Julien Dusonchet, Klodjan Stafa, Darren Moore

Mutations in LRRK2 are one of the primary genetic causes of Parkinson's disease (PD). LRRK2 contains a kinase and a GTPase domain, and familial PD mutations affect both enzymatic activities. However, the signaling mechanisms regulating LRRK2 and the pathog ...

Oxford University Press2014