SPATAX Symposium 2016

 

SPATAX SYMPOSIUM  (June 23-25 2016) 

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The SPATAX network (Spastic and Ataxia) was created in 2000 to foster collaboration between European research teams working on Hereditary Spastic Paraplegia (HSP) and Ataxia. This network accounts for more than 50 research teams that are involved in molecular basis as well as clinical management of these spino-cerebellar neuro-degenerations. So far, SPATAX has enabled gaining a huge amount of knowledge on our diseases. Indeed, over the last decades, genetic studies led to identification of about  30 new genes and for some of them the pathogenic mechanism they lead have been elucidated at a molecular level.

In june 23-25 2016, the SPATAX symposium (Organizers, Pr Alexandra DÜRR & Pr Giovanni STEVANIN)was held at the ICM ( Brain & Spine Institute ), Salepetriere Hospital, Paris for the fifth time. The audience was composed of the HSP and Ataxia worldwide leader groups from Europe, Mediterraean countries, and  North America.

 

TO GRASP THE CONTEXT
(from Klebe S, Stevanin G, Depienne C  Rev. Neuro. Elsevier-Masson 2015, in press)                                                                                                                    

Hereditary spastic paraplegias (HSPs) are genetically determined neurodegenerative disorders characterized by progressive weakness and spasticity of lower limbs, and are among the most clinically and genetically heterogeneous human diseases. These neurodegenerations mainly concern the cortico-spinal tract that drives motor order from the brain to the end of the spine. Neurological disorder more precisely locates along axons of the corticospinal neurons.                                                          

All modes of inheritance have been described, and the recent technological revolution in molecular genetics has led to the identification of 76 different spastic gait disease-loci with 59 corresponding spastic paraplegia genes. One of these genes, when mutated, is able to cause HSP. Autosomal recessive HSP are usually associated with diverse additional features (referred to as complicated forms), contrary to autosomal dominant HSP, which are mostly pure. However, the identification of additional mutations and families has considerably enlarged the clinical spectra, and has revealed a huge clinical variability for almost all HSP; complicated forms have also been described for primary pure HSP subtypes, adding further complexity to the genotype-phenotype correlations. In addition, the introduction of next generation sequencing in clinical practice has revealed a genetic and phenotypic overlap with other neurodegenerative disorders (amyotrophic lateral sclerosis, neuropathies, cerebellar ataxias, etc.) and neuro-developmental disorders, including intellectual disability.  

The most recent advances in the field have provided: i) genotype-phenotype correlations that could help clinical diagnoses of this heterogeneous group of disorders, ii) advances in the knowledge of molecular mechanism at work determined by various SPG genes. The   scheme below sums up various altered functions resulting from  mutated SPG at the level of  the cortico-spinal neuron.

 

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Scheme of cortico-spinal neuron and altered functions in HSP functions                                                              
according to involved genes (from Klebe et al.,Rev. Neurol. 2015)

 

SPATAX MEETING 2016  IN BRIEF      

In keeping in mind that Ataxia and HSP share common features and some forms may occur with the two diseases in the same family, the Symposium alternated research communications devoted to  these neuro-degenerations For both diseases talks dealt with: i) Clinico-genetics,ii) Functional studies pointing out molecular and cellular mechanisms of action, iii) Biomarkers & Therapeutic approach.  Regarding specifically to HSP, the plenary contributions came from Peter BAUER & Rebecca SCHÜLE from Tuebingen, Germany as well as Evan REID from Cambridge, UK. In the light of the functional scheme of cortico-spinal neuron represented above, the hot insights that were debated regarded the functional role of Spastin , the HSP star protein encoded by the SPG4 gene, that is the the most frequently affected gene in families. Indeed Spastin was shown  to be involved in trafficking internal transport machinery as well as nuclear envelope formation; moreover Spastin binds to lipid droplets and affect lipid metabolism. So far this basic knowledge does not result in therapeutic approach.                
For sharp information see https://spatax.wordpress.com/category/meeting-2/

Jean BENARD                                                                                                                                                                 
HSPer Patient,  Scientific advisor of EURO-HSP

 

 

European leader scientists currently involved in HSP researches (basic & clinical aspects):

 

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Rebecca Schüle & Ludger Schöls

 

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Coralie Fassier & Evan Reid

 

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Jamilé Hazan - discoverer of SPG4

 

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Giovanni Stevanin - SPATAX meeting organizer

 

 

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Alexandra Dürr - SPATAX meeting organizer

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