2021 WMS Virtual Congress was a Great Success!
The executive board of the WMS decided to hold another virtual congress in 2021 following on from the success of the first in 2020 with the realisation that there would not be a return to normal in 2021. We wanted to make sure that everyone could plan for the meeting, our members, our sponsors, those who are interested in the teaching course and of course our congress organisers. Our colleagues in Prague needed to know if contracts should be signed and our programme committee if we could expect speakers to travel to Prague. So, the 26th Annual Congress was held virtually on 20-24th September 2021. Again, we had fantastic support from members, delegates, and sponsors with 1600 registrations, 400 abstracts submitted, 10 industry symposia and wonderfully positive feedback via our evaluations and direct messages from attendees.
New for 2021 was the introduction of the ‘live fun social’, where the social experience of the congress was brought to delegates virtually with magic, live musicians and interactive quiz fun. Working with our congress caricaturist and live event illustrator captured fantastic visual dimensions this year!
We have included a selection of congress highlights below and hope that you enjoy reading through them.
PRE CONGRESS TEACHING COURSE
CONGRESS DAY 1
The Opening Lecture was a novel topic and excellent presentation
Inspiring science and invigorating discussions
- Caroline Dog-Iner and Anne-Mice both wanted to decrease the number of animals used in pre-clinical development, but not change the size of it.
- Caroline made a strong point about the physiology of large animals that is closer to human physiology, about longevity, and the importance of large animal models for gene therapy - a point well taken by Annemieke.
- But as stated by this latter, the most important is not so much the model, it is how we use it, how we know its limitation and its strength.
Great format, loved the debates, very engaging!
Very much enjoyed this new format and would like to see Debates again in future conferences.
Live Fun Social was very funny. Quiz, music and magician were excellent!
CONGRESS DAY 2
Genotype-phenotype correlations in valosin containing protein disease: an international multicentric audit, the VCP International Study Group
This is the largest collection of VCP patients described. 223 patients from 175 different families. Due to the large amount of patients, several correlations were confirmed and newly identified.
- ~50% of patients with VCP mutations have scapular winging on exam
- The most compelling genotype-phenotype correlation identified related to the age of onset being earlier in patients with the VCP-R155C mutation versus the VCP-R155H mutation.
Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis
- 7 families with childhood onset of motor neuron disease were identified with dominant SPTLC1 variants.
- The role of primary metabolic disturbances in ALS has been elusive; this study defines excess sphingolipid biosynthesis as a fundamental metabolic mechanism for motor neuron disease.
- Modulating SPTLC1 function or altering sphingolipid metabolism may be therapeutic in ALS
Loss of function mutations in DNAJB4 cause a myopathy with early respiratory failure
- Three families with early onset respiratory failure and axial rigidity were identified carrying homozygous variants in the chaperone protein DNAJB4
- DNAJB4 loss of function in mouse skeletal muscle and myotubes leads to the accumulation of myofilament proteins such as desmin and myotilin.
- DNAJB4 can be added to the growing list of protein chaperones associated with myopathies.
Transcriptomic profiling of paired normal skeletal muscle using bulk RNAseq and snRNAse
- Gene expression is distinct between the tibialis anterior and vastus lateralis from the same individual with ~17% of genes differentially expressed.
- The difference in expression profiles may relate to alterations in cell composition with the TA having more fibroadipogenic progenitor cells and endothelial cells.
- These data are essential to understand the differential susceptibility and progression of distinct muscle groups in muscular dystrophy.
CONGRESS DAY 3
GNE pathogenic variant p.D207V rarely leads to myopathy in homozygotes; GNE might not be the only pathogenic determinant of GNE myopathy
W. Yoshioka; K. Sonehara; A. Iida; Y. Oya; T. Kurashige
- Homozygosity for a rare D207V GNE mutation in Japanese patients
- One asymptomatic patient with normal sialic acid
- 3 additional homozygous cases with very mild features but symptomatic
- possible influence of genetic or environmental modifiers
Muscle ultrasound in COL6-related muscular dystrophy: Patterns and progression
S. Syeda; M. Mohammed; A. Foley; S. Donkervoort; D. Saade; S. Neuhaus; P. Mohassel; D. Bharucha- Goebel; M. Leach; M. Fink; J. Dastgir; C. Bönnemann
Take home message:
- muscle ultrasound is a simple, efficient and bed side technique to assess muscle pathology in neuromuscular disorders
- evocative pattern suggestive of COL6 related dystrophies
- graduation of severity of changes well correlates with clinical stage of the disease
- Muscle MRI could be of help when pathology is very advanced and ultrasounds reaches a floor effect
Efficacy and safety of mexiletine in non-dystrophic myotonias: a randomized, double-blind, placebo-controlled, cross-over study
S. Vicart; J. Franques; F. Bouhour;
- randomised double blind study
- mexiletine lead to highly significant of improved of stiffness compared to placebo
- mexiletine significantly improved time to get up from a chair
- Significant improvement in quality of life
- No serious adverse events noted during the study period
scAAV.U7snRNA-mediated therapy: prolonged dystrophin expression and muscle function correction in adult Dup2 mice L. Gushchina;
- translational research efforts for DMD exon 2 duplications
- skipping exon 2 leads to dystrophin production by re-framing the duplicated transcript (if only one exon is removed) or activation of a trnscriptiopnal start site in exon 5
- AAV U7 was used to deliver a antisense to skip exon 2 in mice
- this approach led to efficient removal of exon 2 in skeletal muscle and heart, with high l
Longitudinal developmental profile of new-borns and toddlers treated for spinal muscular atrophy
- Babies coming from newborn screening, mostly have been treated with nusinersen
- Cognitive development appeared to track at a lower level in already symptomatic children at the time of initiation of treatment
- while there was a clear trend in upwards in their developmental and language score following treatment, this study suggests that that more attention to the neurodevelopmental development of SMA children is required
Efficient modification of DMD gene using PRIME editing
- Experiment PRIME gene editing technology
- Multiple mutations mostly gene transversions
- Efficient in vitro correction of these changes following a single transfection
LATE BREAKING NEWS
Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy
M. Taniguchi-ikeda; E. Bonora; S. Chakrabarty; G. Kellaris; J. Tanboon; I. Nishino; T. Toda; Y. Goto; I. Nonaka; N. Katsanis; F. A. M. Duijkers; R. De Giorgio;
- 15 genes previously identified in MINGIE
- 2 Japanese siblings with severe early presentation with epilepsy and multiorgan involvement
- exome analysis identified novel compound heterozygous mutations in DNA Ligase III
- previous studies had linked this gene to a severe mitochondrial disease in mice
- mt DNA depletion and reduced respiratory chain enzyme activities. However no mtDNA deletions
- 3 additional families identified via international collaborations
- zebrafish studies with lig3 mutations showed impaired gut mobility
- high level of glutamine improved cellular viability and increased mtDNA copy number and might be considered
Biallelic loss-of-function OBSCN variants predispose individuals to severe, recurrent rhabdomyolysis
M. Cabrera-Serrano; L. Caccavell; M. Savarese; A. Vihola; M. Jokela; M. Johari; T. Capiod; M. Madrange; E. Bugiardini; S. Brady; R. Quinlivan; A. Merve; R. Scalco; D. Hilton-Jones; H. Houlden; H. Aydin; S. Ceylaner; J. Vockley; R. Taylor; H. Goullee; E. Ylikallio; M. Auranen; H. Tyynismaa; B. Udd; A. Forrest; M. Davis; D. Bratkovic; N. Manton; T. Robertson; P. McCombe; N. Laing; L. Phillips; P. de Lonlay; G. Ravenscroft;
- First patient Prolonged exercise and heat exposure triggering factors, bi-allelic loss of function in obscurin
- Originally discarded as bi-allelic loss of function variants not rare in gnomAD, but this was more an issue of incomplete curation in gnomAD. Re-evaluation of previous LOF calls revised
- More patients with biallelic loss of function, 6 patients with clear rhabdomyolysis phenotype via international collaborative efforts .
- Possible role of obscurin in calcium handling in skeletal muscle
- Condition to be considered in childhood-early onset severe and recurrent rhabdomyolysis
HOPE-2 Multi-center Randomised Clinical Trial of Intravenous Human Cardiosphere-Derived Cells for Late-Stage Duchenne Muscular Dystrophy
C. McDonald; E. Marbán; S. Hendrix; N. Hogan; R. R. Smith; M Eagle; R. Finkel; C. Tian; J. Janas; M. Harmelink; A. Varadhachary; M. Taylor; K. Hor; O. Mayer; E. Henricson; P. Furlong; D. Ascheim; S. Rogy; P. Williams; L. Marbán.
- cells (cardiosphere) administered intravenously in patients. Action: secretion of exosomes that contain a number of disease ameliorating properties.
- primary efficacy endpoint: performance of upper limb module scale (PUL)
- 150 million cells intravenously every 3 months
- Treatment well tolerated with exception of hypersensitivity, addressed with high dose steroids and antihistamines
- significant decrease of the expected annual PUL decline in the treated patients.
- cardiac MRI showed not only stabilisation of decline, but actual improvement of function
- a pivotal phase 3 study is being planned for non ambulant patients with DMD
The platform looked great and was easy to navigate!