The meeting organized by SPATAX, Erare PREPARE_Ataxia and Ataxia Study Group (ASG) on spastic paraparesis and ataxia in Nice (2019 September 20-21) gathered 160 scientists and patients from 21 countries from 4 continents. It followed a satellite workshop focused on recessive ataxias organized by the Erare PREPARE_Ataxia consortium (10 countries, September 19-20 in Nice).
The 19 seminars, 12 oral presentations from abstracts selection and the 70 posters allowed a lot of exchanges between researchers and to hear the voice of patients.
Acknowledgements: We thank the organizing committee (S Boesch, A Durr, F Santorelli, G Stevanin, M Synofzik, C Tallaksen and B van de Warrenburg), the staff (Marie Biet, Typhaine Esteves, Rania Hilab, Hortense Hurmic, Elodie Petit, Marie-Luce Poupinel) and our sponsors:
Gold sponsors: ICM, SPATAX, DYNACURE, E-Rare PREPARE_Ataxia, Tom Wahlig Foundation
Silver sponsors: ADCA vereniging (Netherlands), Association Française de l’Ataxie de Friedreich (AFAF-France), Associazione Italiana Vivere la Paraparesi Spastica onlus (AIViPS-Italy), Association Strümpell Lorrain (ASL-HSP-France), Connaître les Syndromes Cérébelleux (CSC-France), EURO-HSP, National Ataxia Foundation (NAF-US), Norwegian Association for hereditary spastic paraplegia/ataxia (Naspa-Norway), ROCHE Diagnostics, Spastic Paraplegia Foundation (SPF-US), The Maddi Foundation (UK)
Prices. We congratulate Marc Corral-Juan from Barcelona and Alexandre Pierga / Maxime Boutry from Paris that won the prices for the best Posters on SCA37 expansion and Spg11 physiopathology respectively.
Booklet of abstracts and program: LINK
Debriefing for HSP patients and EURO-HSP: LINK
Live summary of the oral presentations:
1/ The meeting started with a presentation by a representative of the EURO-HSP foundation on the patient’s expectations followed by few words from the CSC association (Ataxia France).
2/ Helene Puccio (Strasbourg) started the scientific meeting with a talk on the modeling in mouse and zebrafish of ADCK3 ataxia and its related mitochondrial dysfunction.
3/ Agnes Rotig from Paris told us how abnormal iron accumulation in FRDA patients can results from reduced palmitoylation of transferrin receptor; an interesting target for therapeutics
4/ Claire Guissart from Montpellier described a novel Gene in recessive ataxias complicated by dysmorphia and corpus callosum atrophy ; ATG7, a key player of autophagy.
5/ Eduardo Balagué from Catalunya succesfully improved the phenotype of a mouse model of FRDA using a AAV9 gene therapy
6/ Andrea del Bondio (Milan, Montreal) connected the abnormal mitochondrial distribution in ARSACS to alterations in calcium homeostasis which led to a preclinical trial in the mouse model with Ceftriaxone with beneficial effects. This worked at presymptomatic and post symptomatic steps.
7/ Frédéric Vaz (Amsterdam) did a fantastic talk on lipids in CNS disorders and described a new HSP gene involved in lipid metabolism: PCYT2 (PE synthesis)
8/ Fanny Mochel (Paris) gave us a nice talk to guide diagnosis and follow up of patients with spinocerebellar degeneration due to abnormal metabolism and emphasized the role of glia in these diseases.
9/ Matthis Synofzik (Tubingen) reported the results of the analysis of Neurofilamemt accumulation in SCA3 mouse and humans.
10/ Alexandra Davies studied AP4 deficiency syndromes and has shown that the disease is leading to a missorting of ATG9 that accumulates and lead to autophagy dysfunction
11/ The first day of the meeting ended with presentations of initiatives at the international level to promote research on these diseases. Rebecca Schule, Alexandra Durr, Matthis Synofzik and Thomas Klockgether discussed on the need to work together with common databases (such as Arca registry), to understand presymptomatic stages and to identify bio markers for treatments.
Next ArCA-global-initiatives.net meeting in Denver 2-3 March 2020.
Next SCA global meeting in Bonn 6-7 April 2020.
TreatHSP is dedicated to HSP registry.
RedCap Spatax database is dedicated to both HSP ans Ataxias since there is a clear overlap between these diseases.
The party at the C’Factory was the opportunity to
discuss further and dance.
Discussions in front of scientific posters
12/ The second day of the meeting started by a talk from Rebecca Schule (Tubingen) that described a new gene on spastic ataxias, RNF170, increasing the number of genes involved in IP3R degradation, together with Erlins, in these diseases.
13/ André van Kuilenburg (the Netherlands) showed us that it is possible to use clinical information to facilitate gene identification. He analysed glutaminase metabolism genes to explain the biochemical anomalies (increased glutamine) he observed in ataxic patients. He suspected a silencing of the glutaminase gene and found a triplet repeat expansion in the 5’UTR
14/ Daniele Galatolo (Pisa) studied a series of ataxic patients mutated on Stub1 with dominant transmission (SCA48). Frequency was 3% and 23% in familial cases. Patients had a complex form of the disease with Huntington’s disease like signs with no phenotype genotype correlation. Much debate came from the fact that it is difficult to be sure of the pathogenicity since recessive mutations lead to SCAR16 and parents are not affected.
15/ Henry Houlden (London) talked about Late onset ataxia with sensory neuropathy and vestibulopathy (CANVAS) that is caused by a non coding AAGGG repeat expansion in RFC1. Gene identification came from genome sequencing showing loss of reads in the region followed by southern blot analysis. This expansion explains 90% of CANVAS patients and 2O% late onset ataxia
16/ Isabel Silveira (Portugal) identified an ATTT repeat expansion in SCA37 patients through the screening of hundreds of candidate repeats in the chromosomal locus segregating with the disease. The repeat is unstable during paternal transmission and is in an intron of DAB1 gene and forms aggregates in nucleus through RNA mediated toxicity. Other repeats of similar nature have also been involved in epilepsy. T>C modification is probably at the origin of the expansion
17/ Juan Bonifacio talked about the physiopathology of AP4 syndromes. AP4 deficiency lead to ATG9 accumulation in the golgi and autophagy impairments. AMPA receptors accumulate in autophagosomes. A role of AP4 is also to help in dynamic transport along microtubules.
18/ Almudena Avila from Catalunya reported that the RFC1 expansion in 78 late onset ataxia in Spain is 10% biallelic and 13% heterozygous with few cases with other repeat nature (AAAGG). Other mechanisms may be implicated then.
19/ Gulin Oz showed us that MRI and MRS are more sensitive to progression of neurodegeneration than clinics in SCAs and can detect premanifests. She is involved in the Ready-SCA project to study cohorts of SCA1 and 3 for imaging biomarkers
20/ Judith van Gaalen from Netherlands showed that SCA3 carriers have cerebral activation patterns that are different than controls by fMRI under specific tasks.
21/ Adam Vogel from Melbourne revealed swallowing and speech difficulties in premanifests Sca2 patients
22/ Bernard Brais from Montreal told us the story of ARSACS and the recent findings towards futur therapeutics with a targeting of neurofilament accumulations.
23/ Frederic Darios showed us how observations in a mouse model of SPG11 in which lysosomal recovery is impaired can bring us to a therapeutic strategy targeting lipid metabolism. Gangliosides and cholesterol accumulate in lysosomes probably as a consequence of the absence of Spatacsin for forming tubules. Targeting gangliosides metabolism improved the phenotype of zebra fish models of spg11 so it is a promising therapeutic strategy
24/ Final debate on therapeutics. Activity is beneficial for neurodegenerative diseases: Patients can do something for their disease themselves.
Dance (Lucy Vincent), See https://spatax.wordpress.com/…/danse-to-improve-your-well-…/
Physiotherapy, vocal training and exergames (Matthis Synofzik).
Botulinum toxin ( Alexander Geurts, Fabricio Diniz),
Trans cranial stimulation (Roderick Maas),
Interferon gamma (Andrea Martinuzzi).
End of the meeting. Thanks to all chairwomen and chairmen and to all the staff.