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Clinical Trials

Clinical Trials

In the last decade over 30 ALS clinical trials have been reported. As yet the only agent that exerts however modest effect on disease progression in patients is riluzole (Rilutek®; AventisParma SA)  Pitfalls and methodological drawbacks of randomized clinical trials have been recently highlighted.

  Major problems comprise:

  • - Uncertain predictive ability of preclinical models: Preclinical tests are almost exclusively performed on mSOD1 rodents. As discussed elsewhere, the validity of this model as representative of sALS in humans have been questioned lately. High background noise in terms of gene copy number and phenotypic variability in transgenic mice hampers the interpretation of data and evaluation of tested agent's effect on survival. mSOD1 rodent models are characterized with huge over-expression (20-40 fold) of human gene compared to the single gene dose effect in human fALS cases. Moreover, in order to extrapolate the data from mouse to human disease, one has to take into consideration still not fully understood differences in motor system anatomy, blood-brain barrier permeability, neurons-to-glial cells ratio and immune response. Finally, the best results in animal studies have been obtained when treatments were tested at the pre-symptomatic stage, the situation that poorly mimics the disease well beyond the symptoms onset characteristic of ALS patients enrolled in clinical trials.
  • - Currently the lack of go-no-go assay neither in preclinical nor in clinical steps limits the trials efficiency. Biomarkers as surrogate end- points are needed that would facilitate the choice of candidate therapies, minimize the costs and, finally, speed up and improve the design of clinical trials.
  • - Inadequate study design in terms of sample size, dosage selection, drug delivery and pharmacodynamics. Sample variables include high phenotypic heterogeneity in ALS patients, low enrollment, and diagnosis delay so that potential treatments start late already.

For the published  information on completed and ongoing clinical trials in ALS for a variety of potential treatments visit ALSTDI database ,,, For the enrolling clinical trials in Italy see AISLA research updates or AIFA OsSc

At he First National Conference on Health Research held on November 8-9 in Cernobbio, within a section "New therapeutic strategies in neurodegenerative diseases" AriSLA's President Dr. Mario Melazzini gave an overview on problems and perspectives concerning ALS clinical trials in Italy and worldwide. The presentation can be viewed at the AriSLA site


European Network of Excellence TREAT-NMD has made available a web-based Regulatory Affairs Database containing national and EU-level legislative documents relevant to clinical trials. With the help of contacts from the European Clinical Research Infrastructures Network (ECRIN), the database now features related contact information for thirteen individual European countries, as well as European-level regulations and other international guidelines. At the national level, resources are available for Austria, Belgium, Denmark, Finland, France, Germany, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland and the UK. Experts with regulatory resources for other countries are invited to come forward with information in order to widen the range of the database.


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