SCIENTIFIC PROGRESS AND DISCOVERIES
- 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.
while no cure are available
- 7000 different pathologies, each of them affecting only a small number of patients.
- 3 to 4 millions of affected people in France and 25 millions in Europa
- Around 80% of rare diseases have a genetic cause
- Web site of the French Rare Diseases Fundation : https://fondation-maladiesrares.org/les-maladies-rares/les-maladies-rares-bis/la-definition-des-maladies-rares/
- 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
- 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
- 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.
xeroderma pigmentosum (xp)
- 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.
100 cumulated years of research
- 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
Chief Medical Officer (CMO)
PR. PIERRE CAU
Chief Scientific Officer (CSO)
PhD, HEAD OF CLINICAL DEVELOPMENT
PhD, Research Project Leader
PhD, Research Project Leader
DVM, PhD, Research Project Leader
Clinical Research Coordinator, Post-Grad degree