Publications de Patrick Aebischer

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In spite of partial success in treating Parkinson's disease by using ectopically placed grafts of dopamine-producing cells, restoration of the original neuroanatomical circuits, if possible, might work better. Previous evidence of normal anatomic projectio ...

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 ...

Retrograde transport of viral vectors in the rodent spinal cord provides a powerful means to administer a therapeutic transgene from the innervated musculature. With the aim of scaling up this approach to non-human primates, we have injected recombinant ad ...

The encapsulation of genetically modified cells represents a promising approach for the delivery of therapeutic proteins. The functionality of the device is dependent on the characteristics of the biomaterials, the procedures used in its confection and the ...

Despite aggressive surgery and post-operative radiation and chemotherapy, the prognosis is poor for glioblastoma patients. Anti-angiogenic therapy with compounds such as endostatin could delay the onset of relapse. However, the short systemic half-life of this proteins as well as the blood-brain barrier makes the use of this therapy difficult for brain cancer patients. The aim of this project is to develop and implant genetically engineered producer cells secreting endostatin that are encapsulated in calciu

Several studies have shown the ability of human immunodeficiency virus type 1 (HIV1)-based lentiviral vectors to infect nondividing brain and retinal neurons with high efficiency and long-term expression of the transduced gene. We show that purified embryo ...

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 ...

Several lines of evidence suggest that phosphorylation of α-synuclein (α-syn) at S87 or S129 may play an important role in regulating its aggregation, fibrillogenesis, Lewy body formation, and neurotoxicity in vivo. However, whether phosphorylation at these residues enhances or protects against α-syn toxicity in vivo remains unknown. In this study, we investigated the cellular and behavioral effect of overexpression of wild-type (WT), S87A, and S87E α-syn to block or to mimic S87 phosphorylation, respective

Current therapy for several forms of anemia involves a weekly regime of multiple subcutaneous injections of recombinant human erythropoietin (hEpo). In an effort to provide a physiologically regulated administration of erythropoietin, we are developing cel ...

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 ...

Biodegradable nerve guidance channels (NGCs) represent a promising alternative to current clinical nerve repair procedures. To be suitable as a NGC material, the polymer system should possess elastomeric properties and degrade at a defined rate without int ...

Parkinson's disease (PD) is characterized by a progressive loss of midbrain dopamine neurons and the presence of cytoplasmic inclusions called Lewy bodies. Mutations in several genes including alpha-synuclein and parkin have been linked to familial PD. The ...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord. We have recently shown that human mesenchymal stem cells (hMSCs) modified to release glial cell li ...

Parkinson disease (PD) is characterized by the progressive degeneration of substantia nigra dopaminergic neurons projecting to the striatum. Since the deficit in striatal dopamine is the main cause of PD symptoms, it appears critical to preserve axon termi ...

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 ...

The gene therapy approach presented in this protocol employs a polymer encapsulated, xenogenic, transfected cell line to release human ciliary neurotrophic factor (hCNTF) for the treatment of Amyotrophic Lateral Sclerosis (ALS). A tethered device, containi ...

Neurotrophic factors hold promise for the treatment of neurodegenerative diseases. Intrathecal transplantation of polymer encapsulated cell lines genetically engineered to release neurotrophic factors provides a means to deliver them continuously behind th ...

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 ...

Although the overabundance of human alpha-synuclein in nigral dopaminergic neurons is considered to play a pathogenic role in Parkinson's disease (PD), it remains unclear how alpha-synuclein leads to neuronal degeneration and motor symptoms. Here, we explored the effect of human alpha-synuclein in the rat substantia nigra following AAV-mediated gene delivery inducing a moderate loss of dopaminergic neurons together with motor impairments. A significant fraction of the surviving nigral neurons were found to

Patrick Aebischer

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Embryonic substantia nigra grafts in the mesencephalon send neurites to the host striatum in non-human primate after overexpression of GDNF

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

Efficient transduction of non-human primate motor neurons after intramuscular delivery of recombinant AAV serotype 6

In vivo calcium deposition on polyvinyl alcohol matrix used in hollow fiber cell macroencapsulation devices

Cell therapy using encapsulated cells producing endostatin

Efficient gene transfer and expression of biologically active glial cell line-derived neurotrophic factor in rat motoneurons transduced wit lentiviral vectors

Viral vectors as a tool to model and treat Parkinson's disease

Channel-Mediated Lactate Release by K+-Stimulated Astrocytes

Mimicking Phosphorylation at Serine 87 Inhibits the Aggregation of Human α-Synuclein and Protects against Its Toxicity in a Rat Model of Parkinson's Disease

A gene therapy approach to regulated delivery of erythropoietin as a function of oxygen tension

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

In vivo performance of a new biodegradable polyester urethane system used as a nerve guidance channel

Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an alpha-synuclein rat model of Parkinson's disease

Synergistic Effects of GDNF and VEGF on Lifespan and Disease Progression in a Familial ALS Rat Model

Wlds-mediated protection of dopaminergic fibers in an animal model of Parkinson disease

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

Gene therapy for amyotrophic lateral sclerosis (ALS) using a polymer encapsulated xenogenic cell line engineered to secrete hCNTF

Central nervous system delivery of recombinant ciliary neurotrophic factor by polymer encapsulated differentiated C2C12 myoblasts

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

Rab1A Over-Expression Prevents Golgi Apparatus Fragmentation and Partially Corrects Motor Deficits in an Alpha-Synuclein Based Rat Model of Parkinson’s Disease