**9.3 Biomarkers in ALS**

There is no diagnostic test for ALS, so diagnosis currently relies upon clinical assessment involving the exclusion of "ALS-mimic" syndromes (such as multifocal motor neuropathy and cervical radiculomyelopathy), causing an average delay of one year from symptom onset to a confirmed diagnosis (Silani et al 2011; Zoccolella et al 2006). In such a rapidly progressive disease this delay is a significant obstacle to potential neuroprotective therapies. ALS is clinically heterogeneous, with multiple subtypes associated with different survival times and symptoms making prognosis challenging. This heterogeneity is also a confounding factor for clinical trials as patient phenotype will impact upon survival data and may influence responses to therapeutic intervention, with some subtypes more responsive to therapy than others (Turner et al 2009). Robust biomarkers would therefore be valuable for the initial diagnosis of disease, the classification of various subtypes, monitoring responses to therapeutic agents and tracking disease progression (Turner et al 2009). Gene expression profiling offers a useful tool for biomarker discovery allowing patient and control biofluids, such as blood and CSF, to be compared on a genome wide scale. These tools have already been employed to improve classification and diagnosis of multiple diseases including neurodegenerative conditions such as Huntington's disease and Parkinson's disease (Borovecki et al 2005; Scherzer et al 2007).

### **10. Conclusion**

In conclusion, microarray analysis has been pivotal in understanding the transcriptional alterations occurring in response to genetic mutations associated with ALS and the sporadic disease (SALS). The cellular model has generated a therapeutic target and transcriptional activation of *Nrf2* is currently being assessed *in-vivo*. Use of spinal cord and peripheral tissues from transgenic mouse models has provided a mechanism to look at the progression of the disease and specifically to identify early changes in the motor neurones and astrocytes. These dysregulated pathways provide future therapeutic targets. In addition, gene expression profiling has allowed crucial insights into the mechanisms affecting different areas of the motor system, with the combination of LCM and microarray technology able to discriminate changes in specific cell types and understand how these affect each other and contribute to disease progression. Finally, the use of human material has begun to allow the distinctions between genetic and sporadic disease to be differentiated as well as providing further candidates for therapeutic approaches. In the future, gene expression profiling of larger, consistently collected patient samples has the potential to generate robust and reliable prognostic and diagnostic biomarkers, which will ultimately be applicable for use in the clinic.
