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Clinical Research

Clinical Research

Clinical research comprises a wide range of interdisciplinary actions that involve human subjects and fall into two general categories: observational and experimental. The former includes in particular epidemiological studies featuring both cohort and case-control studies, behavioral medicine and, in part, a patient oriented research that focuses on medical care and quality of life improvement. This type of research often does not directly benefit the participants, but improves the knowledge on the disease that in turn promotes the development of diagnostic, preventive and treatment options. Studies of genetic causes or genetic predisposition/susceptibility factors, as well as identifications of clinical signs and markers, and development of new techniques to diagnose the disease and measure its progression, are often performed by physicians that follow up the patients. 

Patients contribution to clinical studies involves registration to the disease registries, blood or tissue donations and, finally, clinical trials enrolment.

Joint efforts of clinical and translational research converge into a development and implementation of clinical trials. Trials in humans are the final and crucial step in the development of drugs and treatments where their safety and efficacy are tested. 

Clinical trials

In the last decade over 20 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   

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