Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition, mainly characterized by progressive weakness and wasting of the limbs, the respiratory and bulbar muscles. Respiratory insufficiency leads to a fatal outcome after a mean diseases duration of only three to five years. The disease is characterized by pathological accumulations of a protein called TDP-43, which can be found large cortical and sub-cortical areas of post-mortem ALS brains. No causal treatment for this condition is known to date, and there is a large unmet need to develop new strategies in order to halt or slow down its progression. The aim of this study is to test the safety and tolerability of Tideglusib, a treatment that is already in clinical trials for other neuromuscular conditions, in patients with ALS. It is assumed that this drug may have a significant therapeutic benefit in this population due to his mode of action: In the ALS mouse model, Tideglusib decreases significantly the amount of accumulated TDP-43 proteins within the cells.
Inclusion Criteria:
- Possible, probable (clinically or laboratory supported) or definite ALS according to
the revised version of the El Escorial criteria
- Disease duration < 18 months
- Vital capacity of more than 60% of normal (defined as slow vital capacity, best of
three measurements)
- Age more than 18 years
- On a stable dose of riluzole for at least four weeks or not taking riluzole
- On a stable dose of edaravone for at least four weeks or not taking edaravone
- Capable of thoroughly understanding all information given and giving full informed
consent according to GCP
Exclusion Criteria:
- Previous participation in another clinical study within the preceding 12 weeks
- Proven SOD1- or FUS - mutation
- Tracheostomy or assisted ventilation of any type during the preceding three months
- Pregnancy or breast-feeding females
- Any medical condition known to have an association with motor neuron dysfunction
which might confound or obscure the diagnosis of ALS
- Presence of any concomitant life-threatening disease or impairment likely to
interfere with functional assessment
- Evidence of a major psychiatric disorder or clinically evident dementia precluding
evaluation of symptoms
- Alcoholism
- Cardiovascular disorder/arrhythmia
- Impaired kidney function, defined as creatinine levels of 2.5 x upper limit of
normal (ULN)
- Impaired liver function, defined as aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) of 3 x ULN
- Liable to be not cooperative or comply with trial requirements as assessed by the
investigator, or unable to be reached in the case of emergency