Use of masitinib for treatment of an amyotrophic lateral sclerosis patient subpopulation

#The present invention relates to a method for treating patients afflicted with non-aggressive or moderately aggressive amyotrophic lateral sclerosis (ALS) whose rate of change of the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) prior to treatment initiation is <1.1 points per month said method comprising administering a tyrosine kinase inhibitor or mast cell inhibitor, in particular masitinib or a pharmaceutically acceptable salt or solvate thereof, optionally in combination with at least one pharmaceutically active ingredient.

#Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord [Wijesekera L C, et al. Orphanet J Rare Dis. 2009 Feb. 3; 4:3].

#Approximately two thirds of patients with typical ALS have a spinal form of the disease (limb onset) and present with symptoms related to focal muscle weakness and wasting, in which onset of symptoms may start either distally or proximally in the upper and lower limbs. Gradually, spasticity may develop in the weakened atrophic limbs, affecting manual dexterity and gait. Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solids or liquids. Limb symptoms can develop almost simultaneously with bulbar symptoms and in the vast majority of cases will occur within 1-2 years. Paralysis is progressive and leads to death due to respiratory failure within 2-3 years for bulbar onset cases and 3-5 years for limb onset ALS cases.

#The present invention therefore relates to a method for treating non-aggressive or moderately aggressive amyotrophic lateral sclerosis (ALS) in a subject preferably in a human patient, comprising administering a tyrosine kinase inhibitor, or a pharmaceutically acceptable salt or solvate thereof, to subjects or patients in need thereof. Preferably, a therapeutically effective amount of a tyrosine kinase inhibitor, or a pharmaceutically acceptable salt or solvate thereof, is administered to the subject.

#In one embodiment, non-aggressive or moderately aggressive ALS in a patient is diagnosed through the calculation of the ALSFRS-R score for said patient. Calculation of progression of ALSFRS-R score for a given ALS patient is performed using the following formula: {(ALSFRS-R score at date of first ALS-related symptom)−(ALSFRS-R score at baseline)} divided by {(time between first ALS-related symptom and baseline)}. In the event that ALSFRS-R score at date of first ALS-related symptom is unknown an acceptable estimator is to substitute the upper value of 48 (least disease burden).

#Thus, in one embodiment, the progression of ALSFRS-R score before treatment initiation corresponds to the rate of change of ALSFRS-R score from the date of first ALS-related symptom to time of first treatment (baseline).