Neuromuscular Disorders

C. Weihl, J. Bieschke September 11, 2017

Protein aggregate myopathies (PAMs) are a large class of myodegenerative diseases. Their pathologies are due to the misfolding and aggregation of intracellular proteins in muscle cells. In some cases, these inclusions stain with Congo Red suggesting they are true amyloid. Desminopathies are a prototypical PAM that is caused by dominantly inherited mutations of the DES gene, which codes for the protein desmin.… Read More...

P. Karachunski, J. Dalton, H. Molero-Ramirez, M. Grames September 11, 2017

Childhood onset neuronopathies are a clinically heterogeneous group of disorders. Its original description is known as Brown-Vialetto-Van Laere syndrome and characterized by motor neuronopathy with early onset of bulbar palsy, hearing loss and respiratory failure. Sensorimotor neuronopathy was described later. No treatment was available for this neurodegenerative disorder until recent discovery of riboflavin transporters RFVT3 and RFVT2.… Read More...

A. Guiraud, N. Couturier, V. Buchman, A. Durieux, D. Arnould, E. Christin, S. Janczarski, M. Bitoun, V. Gache September 11, 2017

Centronuclear myopathies (CNM) are a group of congenital myopathies characterized by skeletal muscle weakness, fatigability and atrophy. In affected muscles, myonuclei are abnormally located at the center of mature muscle fibers since they never migrate to the cell periphery as in healthy muscles.… Read More...

L. Charnas, E. Voltz, C. Pfister, T. Peters, A. Hartmann, C. Berghs-Clairmont, J. Praestgaard, M. de Raspide, N. Deconinck, A. Born, G. Baranello, E. Bertini, U. Schara, N. Goemans, R. Roubenoff September 11, 2017

LMI070X2201 is an open-label, multi-part, FIH study of oral branaplam (formerly LMI070) in infants with Type 1 spinal muscular atrophy with 2 SMN copies. The purpose of Part 1 of this study was to evaluate the safety, tolerability, PK, PD and efficacy after 13 weeks of treatment and to estimate the Maximum Tolerated Dose and optimal dosing regimen of enterally administered branaplam in patients with Type 1 SMA.… Read More...

A. González-Jamett, X. Baez-Matus, M. Bui, P. Guicheney, N. Romero, P. Caviedes, M. Bitoun, J. Bevilacqua, A. Cárdenas September 11, 2017

Dynamin-2 is a large GTP-ase that mediates membrane remodeling and actin dynamics in different cell types. It is composed by five highly conserved domains: a GTP-ase domain, a middle structural domain, a PH domain that binds phosphoinisitides a GTP-ase effector domain and a proline-enriched-domain that binds SH3-containing partners.… Read More...

E. Mercuri, J. Kirschner, G. Baranello, L. Servais, N. Goemans, M. Pera, A. Marquet, T. Seabrook, S. Sturm, G. Armstrong, H. Kletzl, C. Czech, D. Kraus, H. Abdallah, L. Mueller, K. Gorni, O. Khwaja September 11, 2017

We have developed a selective, orally-available small molecule, RG7916, designed to modify splicing of the SMN2 gene transcript to increase SMN protein levels throughout the body. A Phase 1 SAD study in healthy volunteers confirmed human proof-of-mechanism of RG7916 with a dose-dependent increase in SMN2 mRNA levels of higher magnitude than with our previous compound RG7800.… Read More...

A. Lopez Kolkovsky, B. Marty, B. Coppa, E. Giacomini, P. Carlier September 11, 2017

NMR allows to quantify in vivo multiple aspects of physiological parameters such as regional perfusion, blood and tissue oxygenation, intracellular pH or high-energy phosphate metabolism. Classical NMR acquisition schemes rarely explore more than a few biological parameters during a dynamic paradigm, such as exercise or leg ischemia, and thus multiple separate experimental sessions are required at the expense of adding experimental variability on biological processes which are already multifactorial, increased length of scan time and patient discomfort.… Read More...

E. Mercuri, R. Finkel, M. Farrar, S. Richman, R. Foster, S. Hughes, W. Farwell, S. Gheuens September 11, 2017

Nusinersen is an antisense oligonucleotide for the treatment of SMA that modulates the splicing of SMN2 pre-mRNA. It is administered intrathecally (12-mg equivalent dose) with 3 loading doses at 14-day intervals, a 4th after 30 days, followed by dosing every 4 months (4 doses over the 15-month study in CHERISH).… Read More...

N. Doorenweerd, C. Bettolo, K. Hollingsworth, J. Hendriksen, E. Niks, V. Straub, H. Kan September 11, 2017

We previously reported on structural alterations in the brain in Duchenne muscular dystrophy (DMD) patients, compared to healthy age-matched controls, namely reduced total brain and grey matter volume. There was an indication that patients missing dystrophin isoform Dp140 in addition to the full length Dp427 had the lowest volume.… Read More...

E. Gargaun, K. Aragon-Gawinska, A. Seferian, T. Gidaro, S. Gilabert, C. Lilien, A. Colcer, K. Boukouti, C. Vuillerot, C. Cances, A. Daron, M. Annousamy, A. De, L. Flet Berliac, H. Armier, L. Fiedler, L. Servais September 11, 2017

Spinraza (Nusinersen) is the first FDA approved treatment in spinal muscular atrophy (SMA). Since October 2016, an open access trial is running in Europe for SMA type 1 patients, and we report here our experience. Sixty-three patients with SMA1 have been consulted since October 2016, 43% were excluded due to lack of standards of care, technical difficulties (spinal fusion, severe scoliosis) or tracheotomy.… Read More...

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