Research Spotlight: World Brain Day!

Posted on July 07, 2021

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" Metabolic profiling in serum cerebrospinal fluid, and brain of patients with cerebrotendinous xanthomatosis"

Cerebrotendinous Xanthomatosis (CTX) is a rare genetic disease that causes problems with lipid storage and metabolism. CTX is an autosomal recessive disorder that causes the CYP27A1 gene that encodes cytochrome p450 oxidase to be ineffective for bile acid synthesis. The main problem is the inability to break down cholesterol to chenodeoxycholic acid properly, and when this happens, several adverse effects may be seen in the body. Certain toxins such as bile alcohols and cholestanols tend to build up in tissues over time which may cause a variety of symptoms to develop. CTX can usually be treated if diagnosed early by oral supplementation with bile acids. If untreated, the disease can result in neurological problems such as seizures, cognitive impairment, and ataxia. Even in patients receiving bile acid supplementation therapy, these symptoms can be seen. A recent study aimed to determine why neurological impairments continue to advance in patients being treated via chenodeoxycholic acid supplementation.

This study was conducted by one of our recent Lipid Leaders, Dr. William Griffiths, and his wife, Professor Yuqin Wang! It is exciting to report more of their work that uses Avanti’s Bile Acids. Patients with CTX were recruited for the study between 2011 and 2019. Samples from nine patients were collected including four who were supplementing with 250mg of chenodeoxycholic acid three times a day. The samples were analyzed for free fractions of oxysterols in serum and CSF using a charge-tagging approach followed by liquid chromatography (LC) and electrospray ionization (ESI) mass spectrometry (MS) with multistage fragmentation (MSn). They were able to differentiate between metabolites that were in 3-oxo-4-ene form and 3β-hydroxy-5-ene form. The study also assessed the cytotoxicity of several bile acids in a mouse motor neuron-like hybrid cell line.

The analysis of metabolic abnormalities in CTX suggested that quantification of sterol metabolites, other than those usually tested for, may have increased utility in diagnostic tests. The consistent lack of 27-hydroxylated sterol metabolites both before and after treatment with chenodeoxycholic acid may indicate that it is a depletion of certain metabolites rather than an increase in toxic metabolites that lead to the neurodegeneration seen in CTX patients. 27-hydroxylated sterol metabolites are important for importing and exporting lipids and other potentially neuroprotective compounds in the brain. The study concluded that a curative approach for CTX may require the complementation of 27-hydroxylated sterol metabolites either through pharmaceutical therapies or by restoring sterol 27-hydroxylase activity in CTX patients.

This study is an important step in continued efforts to understand and treat the rare autosomal recessive genetic disorder CTX. We at Avanti are proud that our bile acid & oxysterol products are being used in research projects such as these to better people's lives. Happy World Brain Day!

Thank you, Dr. Griffiths and Professor Wang for being loyal customers and friends of Avanti! We look forward to seeing what else is accomplished in your research.

To read more about this rare condition, check out the complete research article HERE!