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Translational Research

Translational Research

Translational research constitutes a bridge between basic and clinical research providing means to  transfer scientific discoveries that are generated at the bench, to practical application at the front line of the patient's bedside. This bench-to-bedside approach is actually a two-way process in which basic researchers provide clinicians with new tools to test in clinical context and clinical researchers in turn provide a feed back with their observation on the nature and a progression of the disease.

Translational studies comprise preclinical activities that lead up to a clinical trial. These include direct drug development (validation of potential therapeutic agents in terms of toxicology, pharmacological optimization and scale-up manufacturing) as well as development of tools and services for delivery and monitoring. It also includes the design of clinical trials and the activities that support the conduction of clinical trials such as development of databases and protocols.

In order to sped up the results transfer major communication and sharing of information and resources in the research community are required. Promising ideas for novel therapeutic interventions often encounter difficulties in translation process. This is particularly true for high-risk and highly innovative proposals for rare disorders that do not attract consistent attention and investments. Translational research holds opportunity also for public-private partnership and biotechnological industry that could significantly contribute to therapeutics development by supporting promising results and idea of academic/research teams and, at the same time,  benefit from these joint efforts in having access to novel tools and transformative treatments that can catalyze starting or expanding of their drug development programs.


Limited understanding of ALS pathogenesis along with a lack of diagnostic and prognostic tools impairs efficient detection and treatment of the disease. In fact, the mean diagnostic delay from symptom onset to a diagnosis of ALS has been reported to be between 8 to 15 months. Thus in general  already advanced progression of the disease at the time of diagnosis limits the possibilities for the effective therapeutic intervention and clinical trials. 

The establishment of biomarkers would enable an earlier and correct diagnosis by distinguishing patients with ALS from those with other neurological diseases, as well as discriminate between ALS subtypes, or even detect the susceptibility to ALS in pre-symptomatic stage. Biomarkers could also facilitate the screening for effective therapeutic strategies by monitoring drug efficacy and toxicity during clinical trials. To be used as such, they should  correlate with disease progression as to serve as surrogate end points markers.  This would facilitate go-no-go decisions during clinical trials, increase their safety and efficacy, and overall speed drug development.

Besides the development of imaging techniques such as PET and MRI that can be used to estimate the motor neurons loss, but, to date, fail to detect specific ALS related biological changes in CNS, most of the current research efforts are focused on the discovery of protein biomarkers in biofluids and tissue samples.  Disease specific material (spinal cord, brain stem, motor cortex) is not available for diagnostics or monitoring in ALS. Tissue-based biomarker analysis for ALS is limited to muscle biopsy in living patients and postmortem CNS and muscle tissue samples, and are representative of advanced and end stage of disease.

Advantages of the use of blood and CSF as surrogate tissues for biomarker discovery regard their availability for routine sampling during all stages of disease and well optimized standard operating procedures for sample acquisition, processing, and storage. CSF contains proteins released from different neuronal and non neuronal cell types while blood samples provide also information on systemic events. An important benefit for current and future proteomic studies is the existence of consistent knowledge on their proteome. Some methodological issues must be considered. Potential pathology specific protein biomarkers are likely to be highly diluted in both blood and CSF, the fact that might make difficult to detect the changes in protein levels. Alongside the availability of ever more sophisticated proteomic platforms for biomarker discovery the tools necessary to process a huge amount of data are also being developed.

Urine and saliva represent alternative sources of protein, or, more likely, peptide biomarkers.  These samples are readily available through non-invasive collection. The proteome of these biofluids and potential relevance for ALS pathogenesis and progression is largely unknown.

Several recent studies have identified individual proteins and/or protein panels from blood plasma and CSF that present putative ALS biomarkers, although many of these proteins are not unique for the disease. Lately, a CSF inflammatory profile was associated with ALS pathogenesis displaying a potential  to well distinguish patients with ALS from neurologic disease controls. Further investigations are required to validate these initial findings and pursue the role of these proteins in clinical context as diagnostic or surrogate markers of the disease.

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