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beTherapyB I O T E C H N O L O G Y

Presentation

A panoramic view on obesity- Why are we obese ?

- The “thrifty genome”, a cause for obesity ?

- The pharmaceutical industry approach.

- ObeTherapy’s approach.

- The “expenditure genes” as targets for obesity treatment.

Obesity = imbalance between food intake and energy expenditure

       Food intake        

Energy expenditure(metabolism & physical activity)

The thrifty genome theory(James Neel, 1961)

During thousand of years of evolution, when food was scarce, long periods of famine have selected individuals having organism efficient for food absorption and energy metabolism.

Therefore, individuals with low efficiency for food absorption and energy metabolism became rare.

This explains why we are, in the vast majority, very efficient for food absorption and energy metabolism.

The conjunction of this high efficiency, food abundance and sedentary way of life is directly responsible for obesity.

Appetite/Satiety (CNS)

Absorption

MetabolismGlucose Proteins Lipids

Acetyl-CoA

ATP

Acetyl-CoA

Absorption

Lipids

Obesity

Glucose

Type II diabetes

The pharmaceutical industry approach

•Identify target genes responsible for

obesity.

•Find molecules capable to modulate the

function of these targets.

- Associated 91

- Linkage 201

- Total 292

http://obesitygene.pbrc.edu

Genes linked to or associated with obesity

Obesity genes

Appetit

NPY

Orexin

PTP-1B

AGRP

MG

Axokine

CNTF

Canabinoid

Satiety

OBDB

CCKPOMCMCH

TubbyCART

AgoutyFAT

GLP-1MC4RMC4R

PYY (3-36)

Energyhomeostasis

UCP1

UCP2

UCP3

PKA-II

-Adrenergic R

-Adrenergic R

ACC-2

Famoxin

PTP1B

S6K1

Fat metabolism

PPAR-

SREBP1

C/EBPs

FATPs

PL (Orlistat)MTP

Fat Absorption

All the genes implicated,All the genes implicated, directly or

indirectly,

in energy management (ATP)in energy management (ATP)

It may probably exist hundreds of them !

are genes potentially genes potentially

responsible for obesityresponsible for obesity.

-Most of these genes lack specificity.

-These genes form an extremely complex network and can be redundant. Inhibition or activation of one of these genes can be compensated by others.

-Only in rare cases human obesity is caused by one gene.

PROBLEMS

A new approach for

obesity, hyperlipidemia and

type II diabetes treatment

Understanding

the lean genome

(“expenditure genome”)

in order to treat obesity

The inactivation of the Anderson’s disease gene is responsible for the

lean phenotype

then

overexpression of this gene should give an obese phenotype

Validation of our target:transgenic rabbits which overexpress

our candidate gene are obese

TgControl

Tg

Founders

ObeTherapy Biotechnology, INRA & BioProtein Technologies

• We have set up different assays for this target:- A cellular HTS assay (patent pending)- A cellular manual assay- An in vitro manual assay

• We have validated a target for obesity treatment (patented)

Status on our activity (1)

• We have a list of potential hit compounds obtained by virtual screening (patent in PCT)

This program is conducted in close collaboration with Zambon Group SpA (Milan, Italy)

Recently, we have validated in man another lean

gene as target for obesity treatment :

looking for new partners

Status on our activity (2)

Lean genes allow you to eat

without gaining weight…

Nature did it,

can reproduce it !

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http://www.obetherapy.com

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