RESEARCH, SKILLS & STRATEGY



TO DISCOVER ORIGINAL MOLECULES

Aging, A COMPLEX PHYSIOLOGICAL MECHANISM

  • Aging resulted from a combination of molecular and cellular several events, trigered by both exogenous factors (sun and UV-exposure, tobacco, alcool…) as well as endogenous factors (abormalities in cellular machinery).
  • Among other endogenous one, progerin is the main factor responsible for the accelerated and premature aging in children affected by Progeria (Huchinson-Gilford syndrome).

  • The mutation responsible for Progeria has been described in 2003 by Professors Nicolas Lévy and Pierre Cau, co-funders of ProGeLife.

Most of rare diseases are called orphan diseases
while no cure are available

 

  • Rare diseases are like magnifying glasses allowing the observation and dissection of pathophysiological complex mechanisms, such as aging.
  • Therapeutic strategies designed for rare diseases with aging could benefit the general population and physiological aging.
  • Indeed, these strategies could be usefull during physiological aging to slown down age-related diseases, as well as in the prevention or the cure of age-related diseases.

ProGeLife is developing drugs for two rare genetic diseases with accelerated and premature aging

 ProGeLife is developing drugs for two rare genetic diseases with
                                          accelerated and premature aging
the paradigmatic disease of aging

 

  • 300 living patients worldwide are affected by Progeria and from 300 to 1000 patients are affected by Progeria-like diseases.
  • The accumulation of the toxic protein called progerin in cell nucleus is the main factor of the disease.
  • Children exhibited an accelerated and premature aging leading to death from heart attack or stroke at 13.5 y of mean age

 

 

  • The mutation in LMNA gene leading to Progeria was discovered in 2003 by Nicolas Lévy, Pierre Cau et Claire Navarro in dermal cells from Mégane (deceased on 18th september 2008).
  • No cure is available for Progeria disease

A main factor of cellular aging

  • Progerin biosynthesis resulted from the mutation in LMNA gene encoding type A lamins, fibrous proteins constituting the skeleton of cell nucleus. 
  • Progerin has been shown to be involved in at least 7 among 9 of the major mechanisms leading to cell and organismal aging.
  • Progeria severity could be related to the progerin amount within cell nucleus.

  • During physiological aging, progerin is synthetised without LMNA mutation, by some cells, for example by cells of blood wessel wall, whose abnormalities contribute to the disease. 
  • Progerin has been detected in skin cells from subjects as early as 24 y, and is set as a marker of skin aging.
  • Progerin is expressed in UV-irradiated skin cells.

or « Children of the Moon » disease, Another rare disease with premature aging

  • Around 100,000 patients are affected worldwide and at least 300 in Europe (France, UK, Germany) by this genetic pathology targeting the repair of DNA lesions induced by UV and sun exposure.
  • The cause of the disease is a mutation resulting in the lack or the inactivity of one XP protein : an XP protein cascade is required for the repair of various DNA lesions, among them those resulting from UV and sun exposure.
  • One hour of sun exposure (beach, winter sport) induced 50,000 DNA lesions within each cell of exposed skin. These DNA lesions are not repaired in patients suffering from Xeroderma pigmentosum.
  • XP patients exhibit a very high skin sensitivity to sun and UV radiations, associated with numerous pigmented spots and skin premature aging. XP patients have a very high tendency to develop skin cancers (2,000 to 10,000-fold increase rate over the general population) in regions exposed to sun and UV radiaitions (face, hands).
  • No cure is available for XP disease.
  • Physical photo-protection (helmet, gloves, sunglasses, sunscreen cream, UV-impermeant clothes…) is the only way to prevent or to slow down the development of skin lesions. However such a physical photo-protection has an high social impact and impairs the social life of XP patients and their family. The photo-protection is often discontinued at puberty, thus resulting in skin lesion development.
  • Cryotherapy of actinic keratosis (around 2 pre-cancerous lesions/year without photo-protection), surgical excision of skin cancers result in scars requiring an aesthetic repair and inducing a major psychological burden in patients and family.

ProGeLife développe des médicaments pour deux maladies génétiques rares avec
                            vieillissement accéléré et prématuré

100 cumulated years of research

9 biologistes dont 4 PhD et 2 MD PhD

  • More than 100 cumulated years of research focussed towards rare diseases with accelerated aging
  • Management or involvement in 5 human clinical trials for rare diseases

  • Two hundred international publications, among which 20 with an impact factor above 10

PR. NICOLAS LÉVY

PR. NICOLAS LÉVY

Chief Medical Officer (CMO)
Co-funder

PR. PIERRE CAU

PR. PIERRE CAU

Chief Scientific Officer (CSO)
Co-funder

ÉRIC DESSAUD

ÉRIC DESSAUD

PhD, HEAD OF CLINICAL DEVELOPMENT

Sophie Perrin

Sophie Perrin

PhD, Research Project Leader

Claire Navarro

Claire Navarro

PhD, Research Project Leader

Gaëlle Odelin

Gaëlle Odelin

DVM, PhD, Research Project Leader

Héloïse Laroye

Héloïse Laroye

Clinical Research Coordinator, Post-Grad degree

Pascale Klopp

Pascale Klopp

Engineer