MOdeling to predict the eVolution and trEatment of dominant Optic atrophy and OPA1 gene deficit related diseases pathogenesis (MOVE ONE) & identification of Reactive Oxygen Species and opA1 (ROSA)

P.I. Noélie Davezac

The dominant optic atrophy type 1 (DOA) is a non-treated optic neuropathy whose patients have mutations in the OPA1 gene also involved in Parkinson's syndromes, ataxias and deafness placing this pathology as a study model representing neurodegeneration. We reported that the haploinsufficiency of OPA1, the major mechanism of DOA, leads cells to a pro-oxidative state and that patients have altered expression of oxidative metabolism genes.

These results led to an international patent for the prognosis and treatment of pathologies associated with an OPA1 gene deficiency. The endogenous OPA1 interactome in neurons in primary culture guided us towards two new interactants of OPA1 which we are currently analyzing (ROSA).

Besides, within the area of the medicine of precision, our goal is to predict the evolution of these pathologies and to propose a treatment based on in silico analyzes for a patient thanks to a mathematical model setup with patients’ biological parameters (MOVE ONE).

Collaborators : Joel Bordeneuve-Guibé, ISAE-Supaero, Toulouse University, Toulouse, Pascal Reynier, CHU Angers, Bernd Wissinger (U. Tubingen, Germany)

Publications :

• Merabet N, Millet A, Belenguer P, Bordeneuve-Guibe J and Davezac N. Mathematical modeling of redox imbalance in Dominant Optic Atrophy Type 1. SSBSS 2016 Int Synthetic and Systems Biology Summer School, Volterra Italy. 2016 july 8-14.
• Merabet N, Bordeneuve-Guibe J and Davezac N. Modelling the redox imbalance in Dominant Optic Atrophy: the case of respiratory Complex I. IFAC-PapersOnLine. 2017;50.
• Millet AM, Bertholet AM, Daloyau M, Reynier P, Galinier A, Devin A, Wissinguer B, Belenguer P and Davezac N. Imbalance of the REDOX state in dominant Optic Atrophy: the way of mathematical modeling. AISANH Vol. 5, Issue 1, 2017.
• Millet AM, Bertholet AM, Daloyau M, Reynier P, Galinier A, Devin A, Wissinguer B, Belenguer P, and Davezac N. Loss of functional OPA1 unbalances redox state: implications in dominant optic atrophy pathogenesis. Annals of clinical and translational neurology. 2016;3(6):408-21.

Thesis Awards : Aurélie Millet 2015 Prix de l’Académie des Sciences et Belles Lettres de Toulouse Biologie-Médecine ; Nadège Merabet 2016 Prix de l’Association Française des Méthodes Séparatives.