International Congress Ostheopatic Medicine

Florence 3-6 April, 2011

© copyright 2011 by Patrizia d’Alessio Prof University Paris Sud-11

www.aisa-tx.com

« From enhancement of bioactivity

to enhancer biology »

Aristoteles (384 - 322 a. C.) Problemata,

XXX,« La ragione, la mente, la sapienza »

• 8. Perché il lavoro dei medici finisce col raggiungimento della

salute ?…Ridanno la salute e a questo punto si fermano.

• Forse perché non é possible che da questa condizione ne

derivi un’altra ?

• Oppure, se é possibile, sarà compito di un’altra scienza, e

quello che si riuscirà a fare a partire dalla salute sarà

qualcosa di diverso?

Enhancers

• Definition

• « enhancer » is a region of DNA (regulatory sequence)

that can fix proteins to stimulate gene transcription. The

gene and the enhancer are not necessarily close to each

other and may be on two different chromosomes BUT the

DNA repliement in the nucleus allows them a physical

proximity.

Enhancement of bioactivity

• Some examples:

• Terpenes, such as d-Limonene and menthone induce

bio-physical changes in the stratum corneum (SC)

lipids of the skin, allowing « chemical penetration »

and « percutaneous absorbtion » (i.e. enhancement

of permeability coefficient of an active principle).

Visible surface

Kindly provided by Pr Guimberteau

Surfaces and physical dynamics

• Albert Szent-Gyorgy formulated (1945-57) that thick

layers of interfacial water lie on the surfaces of bio-

molecules and induce physical dynamics

giving rise to electron excitation.

• Should the enhancer activity interfere with the basic

dynamics occurring at the interface (surface) between

bio-molecules and their hydration shell?

To meet an « enhancer »

• Cytoprotective anti-inflammatory actives

• Multiple effects of one molecule

• Trying to understand

• Role of CAM

• Nutrition

STRESS

2002 Endothelium as pharmacological target. P. D’Alessio, Curr. Op. Invest. Drugs, 1720-1724

2003 Aging and the endothelium. P. D’Alessio, Journal of Experimental Gerontology, 165-171

Inflammation accelerates the appearance

of markers associated with cell senescence

CNRS « ICSN »

CHINA « Academy Medical

Sciences »

Cell Biology

Bio-guided selection

Pharmacokinetics Toxicity studies

Proofs

3 Patents

Applications

in vivo

Pre-clinical

studies

Phase I

in vitro

“Hits”

“Leads”

Candidates

Molecules

Platform

Selection by a Screening Platform

2008 New pharmaceutical interventions in aging. P. D’Alessio Rejuvenation Research 11, 399-407

Bio-guided selection permitted to identify 4 AISA out of

2000 tested molecules from some 100 plant extracts

but also found in breast milk,

Three (main) different effects

• Inflammation

• Mood disorders

• Tissue repair

AISA 5203-L inhibition of ICAM-1

following stimulation by TNF-α (HUVEC)

P1 P3 P9

% i

nh

ibit

ion

Inhibition of cell adhesion, a new

mechanism of anti-inflammation

TNF-

serum

levels

are

lowered

The senescent phenotype is reversible

TPA / Hairless skin SHK-mice model used for the study of inflammatory and auto-immune diseases Medeiros R, Otuki MF, Avellar MC, Calixto JB Eur J Pharmacol 2006

TISSUE REPAIR

control TPA Lim + TPA

POH + TPA

Pain and mood modulation

Assessement of the link between

mood and physical alterations • Depressive symptoms and mood alterations increasing with age are now

recognized to be relevant to the development of atherosclerosis.

•Stress is changing also physical parameters

• Enhancers modifying biological surface properties could be interesting in

preservation and restoration of function, diminishing the impact of inflammatory

chronic disease.

Fasciatherapy combined with Pulsology induces changes in blood turbulence

potentially beneficial for the Endothelium. Queré N, Noel E, Lieutaud A,

and d'Alessio P. J Bodyw Mov Ther. 2009 13(3) : 239-45

Enhancer molecule out of food as a potential

anti-inflammatory device :

1/ Nutraceutical intervention

2/ Culinary education

3/ Physical activity

4/ Posturology

5/ Spiritual activity

6/ Meditation

Consciousness through Mouvement

As Lifespan becomes longer

the quality of life becomes important :

health is the key.

As slight physical displacements such as experienced

during Feldenkrais or induced by fascia or osteopathic

manipulations could,

as diet, act as enhancers of specific molecular effects

contained in food components

« Correspondances »

« La Nature est un temple …

• L'homme y passe à travers des forêts de symboles…

• Dans une ténébreuse et profonde unité,…

• Les parfums, les couleurs et les sons se

confondent…

• riches et triomphants,

Ayant l'expansion des choses infinies,

Comme l'ambre, le musc, le benjoin et l'encens,

Qui chantent les transports de l'esprit et des sens. »

(C. Baudelaire)