Muscle spasms in ALS and PLS: understanding the mechanisms and treating the symptoms Investigator: Luc Dupuis, Strasbourg, France Grant: 193 000€ Project duration: three years
Spasticity is one of the major signs of upper motor neuron
involvement in ALS and one of its consequences is the occurrence of
muscle spasms in some patients especially in the upper motor
neuron predominant form of ALS: Primary Lateral Sclerosis (PLS).
Such muscle spasms might be painful, and there are only few treatment options most notably
physiotherapy. To date, no pharmacological treatment for muscle spasms has been specifically
Recent research has shown that spasticity occurring after spinal cord injury (SCI) was due to
alterations in a neurotransmitter called serotonin. While transection of serotonergic axons in SCI
appears a reasonable cause of spasticity, no such mechanism has been identified in ALS-
related spasticity. We have recently observed that platelet serotonin levels were significantly
decreased in ALS patients and that platelet serotonin levels were positively correlated with
survival of the patients. Furthermore, our preliminary evidence indicate that serotonergic
neurons degenerate in ALS patients, that serotonin levels are decreased in the spinal cord of
ALS mice before disease onset and that that the drug cyproheptadine has potent anti-spastic
activity in ALS mice. In all, our previous and current results show that loss of serotonin neurons
is a likely cause of spasticity in ALS and PLS.
(i) understanding the mechanisms leading to serotonergic degeneration and subsequent
muscle spasms in animal models. For this, we will perform genetic, pharmacological,
molecular and electrophysiological experiments that will enable us to define how serotonin
loss leads to muscle spasms in ALS mice.
(ii) translating our findings into a pilot clinical trial to evaluate the effect of cyproheptadine on
muscle spasms in patients. We aim to perform a double-blind, randomized, placebo
controlled clinical trial with a cross-over design of cyproheptadine in ALS patients with
The research will be conducted both in Strasbourg and in Ulm, the project being built upon
complementary expertises in Strasbourg (mouse experiments) and Ulm (clinical trial).
Luc Dupuis is senior researcher at Inserm U692 in Strasbourg in France and guest professor in Neurology at the University of Ulm in Germany. His five major contribution to publications are: Dupuis L, et al. Safety and efficacy of pioglitazone in combination with riluzole in amyotrophic
lateral sclerosis: a randomized, double blind, placebo-controlled trial
Braunstein KE et al. A point mutation in the dynein heavy chain gene leads to striatal atrophy
and compromises neurite outgrowth of striatal neurons. Hum Mol Genet. 2010 Nov Dupuis L, et al., Muscle mitochondrial uncoupling dismantles neuromuscular junction and
triggers distal degeneration of motor neurons. PLoS One. 2009;4(4):e5390. Dupuis L, et al. Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Neurology. Dupuis L, et al., Energy metabolism in amyotrophic lateral sclerosis. Lancet Neurol. 2011
HOSPITAL GENERAL CAMILO CIENFUEGOS JORNADA CIENTIFICA PROGRAMA Sancti Spiritus, 14 al 16 de Noviembre. “Año 54 de la Revolución” . COMISION ORGANIZADORA . Comisión Científica: Dra. Sila Castellón Mortera Comisión de Aseguramiento: Dr. Miguel Oviedo Jiménez. Comisión de Acreditación. Lic Blanca Ruiz Rivero Comisión de Estimulación. Dr. Mario Berea Turiño
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