Michel DIB
CNS Medical Director in Aventis France
Title: ISSUES FOR CLINICAL DRUG DEVELOPMENT IN NEURODEGENERATIVE DISEASES
Biography:
Michel DIB is Neurologist, professor assistant; at the Hospital de la Pitié-Salpêtrière he was also CNS Medical Director in Aventis France.
Received specialist Neurology training at the University of PARIS VI (Pierre et Marie Curie) School of Medicine; Hospital de la Pitie-Salpêtrière, Paris (1990 – 1994).
Master's degree in Human Biology (Pharmacology) from the University of PARIS (1992-1994)
Consultant Neurologist, Department of Neurology, Hospital de la Pitie-Salpetriere, Paris. Between March 95 and 2004,
Patrician Hospitalier, department of Neurology, Hospital de la Pitie-Salpetriere, Paris. Since 2004
Scientific Organizer of the Seminars on Methodology in Neurology in France between1998 and 2014.
Member of the French Society of Neurology
Member of the French Society of Neuro-vascular Medicine
Author of around ninety scientific publications (ALS, dementia, migraine, etc)
Abstract:
Neurodegenerative diseases pose specific challenges for drug development. These diseases typically have a slow and variable clinical course and insidious onset. Symptom expression is only observed when a significant proportion of neurones are already lost. It is important to identify vulnerability factors and other determinants of clinical course in order to be able in the future to select patient populations for clinical trials with a predictable prognosis. The neurodegenerative process itself is not amenable to direct observation and thus cannot be monitored in clinical trials. For this reason, surrogate biomarkers are required to use as outcome parameters. In this respect, magnetic resonance imaging has proved valuable for assessing disease activity and progression in multiple sclerosis. Rating scales are of use as outcome measures, but as these generally measure symptom severity, they are most appropriate for use in assessing symptomatic treatments. Survival has been used with success as an outcome measure in trials in amyotrophic lateral sclerosis, where disease progression is rapid. The optimal outcome measure, the sample size required and the treatment duration need to be chosen in function of the phase of the disease. Potential new treatments can be chosen based upon new knowledge of the genetics and physiopathology of neurodegenerative diseases and, in some cases, screened in transgenic mouse models, although it should be recognised that the validity of these models in terms of treatment response has yet to be established empirically
Experience gained over the last decade allows several lessons to be drawn about how we can anticipate drug development in neurodegenerative disease to evolve over the coming years and several needs to be identified for future research directions.
We need to develop well-validated biological surrogate markers for disease progression in neurodegenerative disease that can be implemented in smaller pilot studies to evaluate experimental treatments. Currently, such proof-of-concept studies are infeasible due to the absence of such markers, necessitating large, long and costly studies for each evaluation. A rapid system of screening promising therapies in pilot studies would speed up the drug development process considerably. Recent advances with MRI in the field of multiple sclerosis suggest that the development of valid surrogate markers can indeed be envisaged.
In conclusion, the lessons of the last decade about clinical drug development in neurodegenerative disease have the potential to shape clinical trials of the future and optimise the chances of identifying therapies that will attenuate progression of these very disabling disorders.