Scripps Florida - The Scripps Research Institute Department of Neuroscience

Department of Neuroscience

FACULTY DIRECTORY

Corinne Lasmézas, D.V.M., Ph.D.

Corinne Lasmezas

Professor

Faculty, Graduate Program

Ph.D., Neurosciences, Pierre and Marie Curie University, Paris, 1995
D.V.M., University of Medicine Toulouse III, 1993

Department of Immunology and Microbial Science

Department of Neuroscience

The Scripps Research Institute
130 Scripps Way 2B2
Jupiter, Florida 33458

Telephone: 561-228-3456
Fax: 561-228-3098

Email:lasmezas@scripps.edu

Research Interests

Neurodegenerative diseases. 

Our laboratory focuses on the study of neurodegenerative diseases, especially those linked to protein misfolding (protein misfolding neurodegenerative diseases, or PMNDs). These diseases comprise Alzheimer’s, Parkinson’s, Huntington’s, prion diseases, fronto-temporal dementia, and amyotrophic lateral sclerosis. None of them are curable. They are all due to host proteins loosing their natural, functional conformation and adopting a new shape that renders them neurotoxic and prone to aggregation.

Prion diseases constitute the prototypic PMND. These rapidly fatal neurodegenerative diseases affect humans and animals and are caused by infectious aggregates of the prion protein PrP, called prions. In humans, prions cause Creutzfeldt-Jakob disease. In animals, the recent epidemic of bovine spongiform encephalopathy in the United Kingdom has caused major turmoil throughout Europe, and later, in other countries such as Japan, Canada and the United States, because the bovine prion disease is transmissible to humans causing variant Creutzfeldt-Jakob disease. The transmissibility of the latter by blood transfusion created a novel public health issue.
Alzheimer’s and Parkinson’s diseases affect 5 and 1 Million people in the USA, respectively. Their incidence has steadily increased with an aging population, having a major impact on public health, society and the economy. Alzheimer’s disease is the 6th leading cause of death in developed countries.

In recent years, it has been discovered that aggregates of amyloidogenic proteins such as Aβ, tau, α-synuclein or SOD-1 involved in Alzheimer’s, Parkinson diseases and amyotrophic lateral sclerosis, respectively, spread from cell to cell in culture and in the living organism similarly to PrP aggregates, showing “prion-like” behavior. There are other features common to these toxic proteins and the way they injure neurons (e.g. toxicity of low molecular weight aggregates, alteration of autophagy, mitochondrial distress).

Our aim is the development of novel, disease-modifying therapeutic approaches for protein misfolding neurodegenerative diseases. We think that this aim will be best achieved by intervention strategies based on blocking prion-like propagation on one hand, and the neurodegenerative process on the other hand. We are pursuing both goals by studying the underlying biology, defining therapeutic targets, identifying active molecules by high-throughput screening and developing lead compounds. The latter two tasks are performed in collaboration with our lead identification and chemist colleagues at Scripps Florida.

Selected Publications

Lasmézas C. I., Deslys JP, Robain O, Demaimay, R., Adjou K.T., Lamoury F., Ironside J., Hauw J-J, Dormont D. (1996) BSE transmission to macaques. Nature 381, 743-744.

Lasmézas C. I., Deslys JP, Robain O, Jaegly A., Beringue V., Peyrin J-M, Fournier J-G, Hauw J-J, Rossier J., Dormont D. (1997) Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein. Science 275, 402-405.

Lasmézas C. I., Fournier J-G, Nouvel V., Boe H., Marcé D., Lamoury F., Kopp N., Hauw J-J, Ironside J., Bruce M., Dormont D. & Deslys J-P. (2001) Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt-Jakob Disease: Implications for human health. Proc Natl Acad Sci USA 98, 4142-4147

Adjou, K. T., S. Simoneau, N. Salès, F. Lamoury, D. Dormont, D. Papy-Garcia, D. Barritault, J. P. Deslys, and Lasmézas C. I. (2003) A novel generation of heparan sulfate mimetics for the treatment of prion diseases. J Gen Virol 84, 2595-603.

Lasmézas, C. I., Comoy, E., Hawkins, S., Herzog, C., Mouthon, F., Konold, T., Auvre, F., Correia, E., Lescoutra-Etchegaray, N., Sales, N., Wells, G., Brown, P. & Deslys, J. P. (2005) Risk of oral infection with bovine spongiform encephalopathy agent in primates. Lancet 365, 781-3.

Simoneau S, Rezaei H, Salès N, Kaiser-Schulz G, Lefebvre-Roque M, Vidal C, Fournier JG, Comte J, Wopfner F, Grosclaude J, Schätzl H, Lasmézas CI. (2007) In vitro and in vivo neurotoxicity of prion protein oligomers. PLoS Pathog 3(8):e125.

Saa P., Sferrazza G.F., Ottenberg G., Oelschlegel A., Dorsey K., Lasmézas, C. I. (2012) Strain-specific role of RNAs in prion replication. J. Virol 86(19).

Zhou M., Ottenberg G., Sferrazza G.F., Lasmézas, C. I. (2012) Highly neurotoxic monomeric alpha-helical prion protein. Proc Natl Acad Sci USA 109, 3113-8.

Karapetyan Y., Sferrazza G.F., Zhou M., Ottenberg G., Spicer T., Chase P., Fallahi M., Hodder P., Weissmann C., Lasmézas C. I. Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as anti-prion agents. Proc Natl Acad Sci USA 2013:110(17): 7044-9.

Zhou M., Ottenberg G., Sferrazza G.F., Hubbs C., Fallahi M., Rumbaugh G., Brantley A., Lasmézas, C.I. Neuronal death induced by misfolded prion protein is due to NAD+ depletion and can be relieved in vitro and in vivo by NAD+ replenishment. Brain 2015:138(4): 992-1008.

Awards, Recognition, Appointments and Honors

1993 Silver Medal Prize, University of Medicine Toulouse III, France.
1993-95 Fellowship Award, French Medical Research Foundation.
1996-00 French National Interdepartmental Expert Committee on Transmissible Spongiform Encephalopathies (TSE), member.
2000-05 French Food Agency, Scientific Board and TSE Expert Committee, member.
2000-present WHO, ad hoc expert.
2002-05 French National Institute of Agricultural Research  (INRA), Department of Animal Health, Scientific Board, member.
2003-09 Government Spongiform Encephalopathy Advisory Committee (SEAC), UK, member.
2003-12 Department for Environment, Food and Rural Affairs (Defra), UK, TSE research advisory group, member.
2004-11 European Medicines Agency (EMA), ad hoc expert.
2006-present USDA, Office of Scientific Quality Review, scientific advisor.
2009-present US Environmental Protection Agency, Science Review Board, member.
2011-present US Food and Drug Administration (FDA), Center for Biologics, Evaluation and Research, panel member.