European HSP Patients Scientific Board Update

1. SCIENTIFIC REPORT GA 2017 Alghero An Update • EUROPEAN PATIENTS SCIENTIFIC BOARD (EPSB) -1- • European HSP meetings gathering specialists & patients are the only way to commit the HSP Patients Scientific Board , in particular SPATAX meeting. • In Paris june 2016, in spite of my request to the French Organizers 1 month before, the SPATAX Symposium Head Quarters did not allow us to meet our EURO-HSP Scientific Board or a small panel of scientists working o HSP. The organizers just invite two of us representing patients to stand up in the audience. They argue that conferences timing was so stringent that they could not! • Of note Tom Wahlig was standing on the podium in an introductive part of the Symposium (his father sponsors the meeting 10 000 E while the ASL-HSP France and the French CSC Association provided each 1500E)!!! Jean Bénard June 17, EURO-HSP GA 2017 Alghero

2. SCIENTIFIC REPORT GA 2017 Alghero An Update • EUROPEAN PATIENTS SCIENTIFIC BOARD (EPSB) -2- • Actually, constitution of common patients registries worldwide represent a mandatory step to foresee any new treatment for a HSP disease type (SPG4 for example). The EPSB will foster a real willingness of “using” this Board to enable it to be effective. • However we must stop thinking about a pure HSP EPSB! Why? • Because now the currenttrend in scientific advancements of rare disxeases is not to focus on a specific group of neurologic diseases (exampleHSP ) but to consider a large body of specific diseases (including not rare ones) in order to pinpoint common features. In our case, Cerebellar Ataxias, Parkinson, MS,AMLS, etc... Jean Bénard

3. SCIENTIFIC REPORT GA 2017 Alghero An Update EUROPEAN PATIENTS SCIENTIFIC BOARD (EPSB) -3- To be sent to EUJPND june 25 2017pending the contribution of concerned patients groups (including EURO-HSP patients) to wide spread and communicate about research impact on their respective ND disease. That is a main aim of EURORDIS! Jean Bénard

4. SCIENTIFIC REPORT GA 2017 ALGHERO SPATAX 2016 & others informations • ADVANCES IN GENETICS • New Generation Sequencing has speeded up the discovery of causal HSP genes • In 2017 • Nearly 120 chromosomal loci have been found about • About 80 distinct genes are identified . • As already assessed, the most represented in families : • SPG4 & SPG3A for autosomal dominant transmission • SPG11, SPG5 & SPG7 for autosomal recessive transmission • Overcoming the divide between Ataxias and Spastic Paraplegias: • Shared Phenotypes, Genes, and Pathways • (Synofzik, & Schule,2017 Movement Disorders 6,. Willey press.) • This evidence strongly suggest a shared vulnerability of cerebellar neurons • and corticospinal neurons for commonpatho-physiologicalprocesses HermienRemmelink & Jean Bénard

5. SCIENTIFIC REPORT GA 2017 ALGHERO SPATAX 2016 & others informations ADVANCES IN PHYSIO-PATHOLOGY  Extreme genes heterogeneity reflects distinct physio-pathological mechanisms at work in the cortico-spinal neuron Physiopathologymechanisms Klebe, Stevanin & Depienne. Rev. Neurol ,2016 HermienRemmelink & Jean Bénard

6. SCIENTIFIC REPORT GA 2017 ALGHEIRO ADVANCES IN PHYSIO-PATHOLOGY Novario G. et al, Science 2014 • SPG-encoded proteins, to exert their biological activity, interact between themselves or with other proteins • SPG-encodedproteins form a biological network that, if not functional, also operate in other neurological diseases: cerebellum syndrome (CS) or Amyotrophic Lateral Syndrome. • This can explain, in families, variations of clinical expression and may reflect observed “passage” from HSP to CS

7. SCIENTIFIC REPORT GA 2017 in ALGHEIRO FROM PHYSIO-PATHOLOGY TO TREATMENT