Which medications in the drug class Bile Acids are used in the treatment of Cerebrotendinous Xanthomatosis (CTX)?

Updated: Jun 20, 2019
  • Author: Robert D Steiner, MD; Chief Editor: Maria Descartes, MD  more...
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Answer

Bile Acids

The primary treatment is CDCA, which was initially used for treatment of gallstones. In the United States, CDCA is available as Chenodal and is distributed by prescription by Dohmen Life Science Services (1-866-758-7068). The typical adult dose is 750 mg/d or 10-15 mg/kg/d orally divided 3 times daily. [7]

Treatment with CDCA has been found to normalize bile acid metabolism and to slow, halt, and even reverse problems associated with cerebrotendinous xanthomatosis. In several well-documented studies, the bile acids and metabolites in plasma, bile, urine, and cerebrospinal fluid (CSF) concentrations of cholestanol have normalized after as little as 4 months of treatment. [7]

Clinically, neuropsychologic and peripheral neurologic symptoms improve, as do effects on bone mineralization.

In a landmark study, dementia was found to improve in 10 of 12 patients with cerebrotendinous xanthomatosis after initiating treatment with CDCA, with strong improvements in mentation, speech, orientation, and memory. [7] Corresponding improvements were seen in MRI and EEG findings. Xanthoma and cataract development were nonprogressive but have not reversed with CDCA administration. Biochemical changes include reduced serum cholestanol levels and increased CDCA levels. [76] Further studies have confirmed and expanded on these findings. [61]

After significant neurological pathology is established, although pharmacologic treatment is recommended, [77] the effect can be limited. [61] A recent study demonstrated patients who started treatment later had a worse outcome than those who started treatment earlier. [78] A subset of patients continue to deteriorate despite treatment, although, in select cases, even late institution of treatment may lead to clinical improvement. [79, 17, 78]  The effect of treatment on cataract progression is described in one study. [80]

  

Generally, CDCA appears to be safe, although hepatoxicity has been reported in at least one infant. In that case, dose reduction was successful. [81]  

In March 2015, cholic acid (Cholbam) was approved by the FDA for bile acid synthesis disorders caused by a single enzyme defect. Cholic acid has been rarely used an alternative to CDCA to treat children with cerebrotendinous xanthomatosis. [72] Currently, there is insufficient evidence to recommend its routine use in cerebrotendinous xanthomatosis.

Chenodiol (Chenodal)

Primary bile acid synthesized by the liver. Known to reduce biliary cholesterol secretion. Available as an orphan drug in the United States for treatment of cerebrotendinous xanthomatosis. Generally appears to be safe, although hepatoxicity has been reported in at least one infant. In that case, dose reduction was successful.


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