Swansea University has developed an integrated Mass Spectroscopy (MS) platform for the quantitative and structural determination of cholesterol metabolites in biological systems. The Liquid Chromatography (LC) MS technology utilises quantitative charged tags that allows for the identification of steroid molecules. The technology is substantially more sensitive than existing methodologies with a capacity to quantify a greater number of steroids.
The research group at Swansea University have established that endogenous cholesterol metabolites can have a neuroprotective and a neurotoxic effect on motor neurons. In addition, steroid analysis of patients with mutations in enzymes involved in cholestenoic acid metabolism also implicated this cholesterol metabolism pathway in genetic diseases concerned with steroid metabolism. Samples from patients with Cerebrotendinous xanthomatosis (CTX) showed very low levels of all cholestenoic acids. Further, steroid analysis of samples from patients with hereditary spastic paresis (SPG5) and infants with Oxysterol 7α hydroxylase (O7AHD) deficiency showed an excess of steroids 3β-HCA and low levels of toxic steroids 3β,7α-diHCA.
Swansea inventors have focused on the medical opportunities for this technology as they have identified molecules with neuroprotective activity and abnormal cholesterol metabolite levels in a range of neurodegenerative diseases. Cerebrotendinous xanthomatosis (CTX) is an inherited disease in which affected individuals cannot make bile acids. As children grow older they make present with a range of symptoms including cataracts, abnormal movements, intellectual disability and cholesterol deposits in the brain. In conjunction with the Karolinska Institutet in Sweden, Swansea researchers have shown that plasma samples from patients with CTX showed very low levels of all cholestenoic acids. Further, abnormal cholesterol profiles have been identified in the Motor Neuron Disease (MND) related illness hereditary spastic paresis. A spin out company called CholesteniX has been formed to commercialise the biomarker and therapeutic potential of this technology for MND and other neurodegenerative diseases. Swansea is in discussions with a number of commercial parties who have expressed an interest in this technology. The consensus view now is that most neurodegenerative diseases (e.g. Alzheimer's and Parkinson's diseases) may be developing for anything up to decades before physical symptoms start to appear. Early diagnosis and treatment in this area may hold out the hope of slowing progression sufficiently to avoid late stage diseases, saving the NHS and the economy millions of pounds in treatment and care and benefiting many thousands families with affected individuals.
Patent applications have been filed for the steroid detection method (GB1215924.0) and the diagnostic and treatment for MND (GB1303589.4). Swansea is seeking companies wishing to license this technology or collaborate in co-development.