"Café des Sciences" on April 21st - Marie Françoise Chesselet
Café des Sciences on April 21st
Speaker : Marie-Françoise Chesselet, MD, PhD
Title : Parkinson’s disease : yesterday, today and tomorrow
Subject : fundamental and therapeutic research on Parkinson’s disease
The invited speaker for this new edition of the French "Café des Sciences" was Marie-Françoise Chesselet : the Charles H. Markham Professor of Neurology and the Chair of the Department of Neurobiology in the David Geffen School of Medicine at UCLA. She received her MD and PhD degrees from the University of Paris VI, France, where she completed her PhD thesis in the laboratory of Jacques Glowinski and became a Charge de Recherches at the CNRS, the National French Research Agency. She was a Visiting Scientist in the laboratories of Ann Graybiel at MIT and of Michael Bronstein at the NIH before joining the Faculty of the Medical College of Pennsylvania and then the University of Pennsylvania. In 1996, she moved to UCLA were she directs the APDA : Advanced Center for Parkinson’s Disease Research, the NINDS-funded UCLA Morris K. Udall Center of Excellence for Parkinson’s Disease Research and the NIEHS-funded Center for Gene Environment in Parkinson’s Disease.
Pr. Chesselet first gave an updated overview of the scientific knowledge regarding Parkinson’s disease, its causes and symptoms. This neurodegenerative illness affects the motor zones of the brain. It is characterized by muscle rigidity, slowness or even loss of movement in the patient. These symptoms stem from the loss of activity of a particular population of pigmented brain cells : the dopaminergic neurons. These neurons get their name from their ability to produce a neurotransmitter called dopamin. They are located in a region of the brain called substantia nigra and composed of pigmented melanin-containing cells. As the disease progress, these neuron loose their activity and stop producing dopamin. The drop in dopamin concentration causes the motor impairments the patients suffer from.
The fundamental causes of Parkinson’s disease are not well-known. 5 to 10% of the patients suffer from a form of the disease that has genetic causes but the causes are otherwise often unknown. Previous studies have shown that the loss of activity in dopaminergic neurons is in most cases due to the accumulation of a protein called alpha-sinuclein in these cells. These proteins aggregate in proteic complexes called Lewy bodies that damage the cell.
Pr. Chesselet then presented the different therapeutic approaches currently in use to treat the symptoms associated to Parkinson’s disease, in particular L-dopa injections and direct physical stimulation through the use od deep intracranial electrodes. L-dopa is a precursor molecule for dopamin that can cross the blood brain barrier and thus be converted in dopamin in the brain after having been injected in the blood stream. This treatment reduce the symptoms of Parkinson’s disease but triggers the apparition of dyskinesia : the involuntary movements that are often associated with Parkinson’s disease. Another solution consists in introducing an electrode in the patient’s brain in order to stimulate specific regions of the deep brain, thus reducing both symptoms and unwanted secondary effects.
Research in Pr. Chesselet’s lab focus on the study of early stage symptoms of Pakinson’s disease such as sleep loss or cognitive and emotional troubles. By being able to detect the disease in an earlier stage of its development, it would be possible to test protective treatments aimed at reducing or stopping the loss of dopaminergic neurons. These studies are based on animal models and aim to describe the cellular and molecular processes responsible for the development of the disease during its early stages. Several therapeutic leads are currently being followed in collaboration with biotech companies. The environmental parameters that trigger the development of the disease are also being studied. For example, exposition to some pesticides could play a role in contracting this disease.
The discussions that followed this presentation shed the light on the perspectives and difficulties associated with research on Parkinson’s disease, such as the lack of funding as compared to what is spent on Alzheimer’s disease for example. Due to the lack of an efficient treatment to cure the disease and not just address its symptoms, the research on early-stage diagnostic is not considered as a priority. On the scientific side, the study of sub-populations of patients - such as those suffering from a genetic form of the disease - can sometime offer precious information on the general mechanisms of the disease. The transgenic line of mice that was engineered in Pr. Chesselet’s lab also constitutes a breakthrough in this field and should be of great benefit for the development of therapeutic or protective treatments in the future.