Olga Corti ICM

Olga Corti, PhD is a Research Director at the Institut du Cerveau et de la Moelle épinière (ICM) located in Paris, France. Olga is an expert in the functional analysis of protein products of Parkinson’s genes with a focus on mechanisms of mitochondrial quality control. We asked Olga some questions about her research and ICM’s role within PD-MitoQUANT.

Within Parkinson’s research, which cell types and mechanisms are most interesting to you at the moment and why?

Parkinson’s disease (PD) is due to the gradual loss of specific neuronal populations, particularly those that produce the neurotransmitter dopamine in a deep structure of the brain called substantia nigra. We still do not understand why these neurons die, and it is essential that we do so if we want to find out how to prevent this degenerative process. Until recently, scientists have only been able to study these neurons post mortem, on brains dissected after the death of the affected people. This has greatly limited the investigation of the mechanisms that are responsible for their special vulnerability. Thanks to remarkable discoveries in the past ten to fifteen years, it has become possible to generate human neurons in a dish, starting from any cell type of the body of an individual. Now we can study dopaminergic neurons from people affected by the condition compared to those from non-affected individuals, or to other neuronal types that are spared in the disease, and try to understand what goes wrong. We are currently using this model in our team at ICM, together with complementary models, such as neurons from mice carrying mutations in specific genes responsible for familial forms of PD. Our research is focused on the investigation of mechanisms related to mitochondria, which are subcellular compartments devoted to the production of the energy necessary to sustain neurons and ensure their function in neurotransmission. There is increasing evidence for an involvement of this organelle in Parkinson’s, fuelled by recent breakthroughs in the field of genetics. We are interested in understanding how mutations responsible for familial forms of PD affect the mitochondria, and with what consequences on the ability of the neurons to respond appropriately under stress conditions. In the brain, neurons establish intimate interactions with other cells types, the glial cells, which surround and support them in their function at various levels, and which are also strongly reliant on mitochondria. Therefore, we are also studying the impact of genetic mutations on glial cell biology in order to evaluate whether these cells may contribute to neurodegeneration in PD. 

 What are the big questions or current challenges in this area?

At the level of biological mechanisms, we need to better understand what renders specific neuronal populations susceptible to degeneration in PD. We, thereforeneed to learn more about the complex interplay between genetic variations modulating the risk for PD, environmental influences and the morphological and functional specificities of the vulnerable neurons. In addition, we will have to gain a clearer understanding of the primary cellular processes that drive the condition, and whether they are shared between different PD forms or specific to some of them. For example, mitochondrial dysfunction has emerged as a central mechanism in PD forms due to mutations in specific genes, such as PINK1 and PARK2, but whether it plays a primary role in disease forms due to the abnormal deposition of alpha-synuclein is yet to be determined. Gaining insight into these questions will have important implications for the development of therapies adapted to each disease type. From a therapeutic perspective, one of the major challenges is to find biological markers of very early changes in the disease process. By the time the first motor symptoms of PD appear in an individual, he has already lost more than 50 % of the relevant neurons in the brain. While research advances towards the identification of treatments to slow the neurodegenerative process, it will be fundamental than we learn how to identify people with a high risk of developing the disease before they show the first visible signs. 

Why is PD-MitoQUANT an exciting project for the ICM? 

 PD-MitoQUANT is a great opportunity for us to move beyond our current studies, contributing to a common effort aimed at clarifying the relevance of mitochondrial dysfunction in PD. Bringing together experts with different backgrounds and viewpoints from academia, industry and patients organization is a major asset for impactful research in this complex field. We are grateful to the possibility of sharing views, ideas and expertise and creating synergies with the other partners of the consortium. PD-MitoQUANT provides also an opportunity for the different contributing investigators at ICM to strengthen ties and move forward towards common objectives, and I look forward to it.