Molecular pathway analysis of Amyotrophic Lateral Sclerosis by genome-wide expression profiling of human blood and skin fibroblasts.

ALS is an adult-onset, disabling and fatal disease characterized by progressive
degeneration of motor neurons in brain and spinal cord. No cure is available
for ALS and the median survival is 3 years. There is no definitive diagnostic
test for ALS available and other conditions can resemble ALS clinically. The
diagnostic delay is more than one year and misdiagnosis is common. In
approximately 10% of patients, ALS occurs in families. Familial ALS is
clinically and pathological indistinguishable from sporadic ALS. The
pathogenesis of ALS is unknown but there is convincing evidence that several
molecular pathways play a role.

The two objectives of our proposal are: (i) to identify specific gene
expression profiles in blood and fibroblasts from patients with ALS or
ALS-mimic in order to improve diagnosis and measure disease progression; (ii)
the identification of genetic determinants linked to disease-associated
expression profiles.

First, gene expression profiling is performed in ALS patients and ALS-mimic
patients leading to specific patterns (functional biomarkers). The ALS-mimic
patients will subsequently determine the sensitivity and specificity for ALS.
Molecular pathways involved in riluzole treatment will be identified by
comparing gene expression before and after treatment. Any findings will be
confirmed in biopsy material. Lastly, when specific profiles are observed we
will genotype SNPs in differentially expressed genes to identify the genetic
basis for the functional biomarkers.

Risks in participating in this study is associated with the risk performing a
venapunction. This is a rather save and frequent performed exercise with
uncommon complications. The procedure is not time consuming.