A Novel Diagnostic Test for Early Detection of Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the gradual loss of motor neurone in the brain and spinal cord, resulting in progressive weakness of voluntary muscle, and variable fronto-temporal dementia. The diagnosis of ALS is largely clinical and difficult in its early stages. The lack of a specific diagnostic test is challenging for patients and doctors alike, delays treatment, and complicates enrollment into clinical trials. The goal of this project is to develop a diagnostic test for ALS by taking advantage of ‘RNA-cleaving fluorogenic DNAzyme (RFD)’ technology that Professor Li’s group at McMaster University has established. RFDs are man-made single-stranded DNA molecules designed and selected to catalytically cleave an attached fluorogenic substrate when exposed to biological fluids from diseased but not control patients, in this instance ALS patients but not controls. We will pursue two specific scientific goals. First, we will exploit a powerful technique, known as “in vitro selection”, to isolate and expand ALS-specific RFDs from a DNA pool containing ~10 quadrillion candidates. Second, we will examine diagnostic utility of individual RFDs using blood and spinal fluid samples from ALS patients and healthy donors.
Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging
The only approved ALS medication riluzole offers minimal benefit to ALS patients, and therefore, there is an urgent need to develop more effective therapeutic agents for this disease. Although the focus of this project is to develop a diagnostic test for early detection of ALS, one likely outcome is the identification of ALS-specific biomarkers that can serve as potential targets for future drug development. Moreover, the aptamer sequences of the detecting probes also have the potential to be developed into therapeutic agents for ALS.
The direct outcome of the project is the possible discovery of novel DNA-based molecules that can be used to set up a test for early detection of ALS. A likely outcome is the identification of novel biomarkers for various forms of ALS, which may offer a great opportunity to develop next-generation therapeutics for ALS treatment. A possible outcome is the identification of DNA molecules that can be further developed into therapeutic agents.