Scientific Research on CADASIL

Teamwork with a message of Hope

Scientific research on CADASIL is dynamic and ongoing between teams of researchers from CERVCO, genetic laboratory of Dr. Joutel from INSERM and partnership with the international network of Leducq Foundation since 2012. Results of the research work are promising. Each year, association members are updated during the General Assembly Meeting of new advances: more accurate description of symptoms, additional knowledge gained through 7 Tesla MRI, better clinical results thanks to animal models etc.

 
Clinical research

In France, clinical research is carried out by the team of Professor CHABRIAT under CERVCO- Centre de Référence des maladies Vasculaires du Cerveau et de l’Oeil (Reference Center of Vascular Diseases of Brain and Eye). He continued the program from Professor BOUSSER. The medical team is based in the Neurology Department of the Hospital Lariboisière in Paris.

Since the disease was discovered, several studies have been conducted to gain knowledge of different symptoms and their evolution: study on the contractility of vessels under MRI, study of  blood pressure change during 24 hours cycle, use of 7 Tesla MRI, study of neurovascular coupling, etc.

As part of clinical research, a major accomplishment was the budget approval of the Hospital Clinical Research Protocol (PHRC- Protocole Hospitalier de Recherche Clinique) launched in 2003. This study enabled a monitoring program, centralized at Lariboisière Hospital, of over 200 patients for approximately 7 years.

Results of various patient studies, such as MRI exams, psychological testing, etc., have been collected on a periodic basis, storing into a significant database, which is used for research of CADASIL and development of therapeutic strategies.

The same program is undergoing in Germany. In total, it provides monitoring of more than 400 patients.

Although this PHRC program has ended, the database is constantly being updated with  results collected during patients consultations at CERVCO.

The program objective is to be ready for a therapeutic evaluation strategy in support of pharmaceutical companies which are developing molecules matching treatment needs identified for CADASIL.

Determining more precise MRI markers will be critical in the future. In late 2008, a research project was launched with the Atomic Energy Commission CEA (Commissariat à l'Energie Atomique) based in Saclay by a member of the CERVCO team. Use of 7 Tesla MRI allows more accurate visualization of the brain and its small vessels..

Many patients (30-40%) complain of apathy (general lack of motivation) with CADASIL. It is an important symptom of the disease, which has been recognized thanks to a study conducted by a team of psychologists at CERVCO.

Basic research

Early genetic research has succeeded in identifying NOTCH3 gene on chromosome 19 to be responsible for the disease and developing a reliable test to confirm its diagnosis.

To date, the work of Dr. Anne Joutel’s team (from INSERM Laboratory of Professor Tournier-Lasserve) is primarily directed towards understanding how small vessels of the brain are functioning, normal role and Notch3 signaling pathway, physiopathological mechanisms of  CADASIL and identifying therapeutic strategies for the disease.

A “proof of concept” clinical trial is underway on mice, in collaboration with a pharmaceutical company. This test constitutes the first tangible hope for obtaining a first concept of preventive medicine, provided it will pass necessary requirements for the application from mice to humans and approval for market distribution.  

International research

Research on CADASILis sponsored by the Leducq American Foundation (Ellis Company). Under its support, an international network between different teams has been established. In Europe, it is coordinated by Dr. Joutel.

To learn more  

For more information on Research, please refer to meeting minutes of medical conferences during annual general meetings of CADASIL France Association. Here. ♦