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From: TSS ()
Subject: SUCCESSFUL MODELING OF CREUTZFELDT- JAKOB DISEASE
Date: December 1, 2005 at 8:16 am PST

##################### Bovine Spongiform Encephalopathy #####################


CJD WATCH MESSAGE BOARD
TSS
SUCCESSFUL MODELING OF CREUTZFELDT- JAKOB DISEASE
Thu Dec 1, 2005 09:06
70.110.89.187


SUCCESSFUL MODELING OF CREUTZFELDT-JAKOB DISEASE

Paris, November 26, 2005: BIO-MODELING SYSTEMS, the leading Predictive

Integrative Biology company is invited to present, in Europe* on December 2nd 2005 and

in the USA** on December 9th 2005, major achievements in the understanding of Prion

(mad Cow) disease, end point of a joint scientific program implemented and carried out

by BMSystems’ team of integrative biologists and the C.E.A. Neuroprion research team

(coordinator of the European Centre of Excellence on neurodegenerative diseases) over a

12 months period. The depth of knowledge generated and the rapidity achieved through

this joint effort in the understanding of a complex disease demonstrates the strong

impact Predictive Integrative Biology coupled to Experimental Biology will have upon the

management and success rate of the Pharma Industry’s R&D programs. A joint

publication, scheduled for release beginning 2006, is underway.

BIO-MODELING SYSTEMS http://www.bmsystems.net/ demonstrates for the 4th time

in succession its ability to produce high precision predictive biological models directly

leading to the discovery of new physiological pathways and new targets in the general

context of highly complex human diseases such as neurodegenerative disorders

(Creutzfeldt-Jakob [mad cow] Disease, Alzheimer disease, etc…)

If available, we invite you to come to these presentations and have a talk with our CSO,

Dr. François Iris, to discover and/or discuss the operational outputs of our Predictive

Integrative Biology CADI™ methods and tools.

In the meantime, we urge you to take a look at one of the model’s 8 predictions,

validated in vivo, that was presented by the C.E.A. scientific team at the Prion

2005 Conference in Düsseldorf (October 19-21, 2005). The document is

available on our website.

The development of Creutzfeldt-Jakob Disease (CJD) implicates the prion protein

together with three types of cells that constitute extensive populations undergoing

complex interactions in the brain: the astrocytes, the microglial cells and the neurons.

The molecular mechanisms of CJD pathogenesis remain unknown.

Using its CADI technology, Bio-Modeling Systems has constructed a theoretical model of

the disease. This model describes new pathways, together with their associated

molecular targets, explaining in part the molecular mechanisms associated with CJD

pathogenesis and disease progression.

Three of these targets, hitherto never described in prion diseases nor in other

neurodegenerative disorders, have been experimentally tested, both in vitro and in vivo,

by the research team of Professor Deslys at the CEA (Fontenay-aux-Roses), coordinator

of the European Centre of Excellence on neurodegenerative diseases.

Two of the targets experimentally studied were shown to undergo substantial

modifications, predicted by the model, both in cells infected in vitro and in mice infected

in vivo. In accordance with the model’s prediction, these modifications first appear in the

neurons and later in activated astrocytes.

These results demonstrate for the very first time that a theoretical model can predict

novel pathways and molecular targets specifically associated with the pathogenesis and

the progression of prion diseases.

*: The Franco-Quebecois Bio-Informatics International Conference, taking place within

the European Biotech Crossroads meeting held in Lille and Paris, form November 28th

2005 to December 2nd 2005.

**: The CHI’s international conference on “Analytical Methods for Metabolic Profiling:

Solving Analysis Problems" in Orlando, Florida, on December 9th 2005.

Do not hesitate to contact us for additional information

Best regards

Manuel GEA

Co-founder & CEO

BIO-MODELING SYSTEMS

Predictive Integrative Biology

26 rue Saint Lambert

75015 PARIS FRANCE

+33 6 83 06 12 72

email: manuel.gea@bmsystems.net

http://www.bmsystems.net/

http://www.bmsystems.net/download/BMSYSTEMS-major-progress-in-prion-disease.pdf

New insight in prion pathogenesis : from theoretical model of

neuropathogenesis to experimental evaluations

1Lenuzza N., 1Charvériat M., 1Buon J.-G., 1Picoli C., 3Lampe P.-H., 3Santamaria P., 1Correia E.,

1Freire S., 2Benhamida S., 3Iris F., 1Deslys J.-P., 1Mouthon F.

1CEA/DSV/DRM/GIDTIP, Fontenay-aux-Roses, France

2Pôle Santé-Biotechnologies Ecole Centrale Paris Châtenay-Malabry, France

3Bio-Modeling Systems, France

Neuropathogenesis of prion diseases involve, on one hand, the prion protein itself and, on the other hand, neurons, astrocytes

and microglial cells. Molecular mechanisms remain unknown. Integrative analysis based upon literature has allowed us to

develop a theoretical model of prion neuropathogenesis. To evaluate the neuropathological mechanisms predicted by this

theoretical model, we focused our experimental study on three original targets neither described in prion fields nor in

neurodegenerative diseases.

Overview of the computer-assisted model-building process

The model result from the systematic destruction of ‘working

hypothesis’ arising from the integration of published information into

an indexed database. The hypotheses that could not be destroyed

are merged into ‘meta-hypotheses’ that are in turn subjected to the

destruction process.

Theoretical description of the prion pathogenesis in the brain

This model predicts a simultaneous implication three cells. In contact

with neurons, PrPres would be deteriorated into small peptides,

which would fix on calcium channels of the three cellular partners. It

would disrupt the equilibrium between these cells, and lead to

neurodegenerative lesions.

Definition of the theoretical model of prion

neuropathogenesis

Results

snip...full text ;


http://www.bmsystems.net/download/Communication-model-PRION-BMSystems-CEA.pdf

TSS

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