Cerebrotendinous Xanthomatosis (CTX) Medication

Updated: Dec 08, 2021
  • Author: Austin Larson, MD; Chief Editor: Maria Descartes, MD  more...
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Medication Summary

The treatment of choice in CTX is CDCA replacement therapy to inhibit the flux of cholesterol into the bile acid synthesis pathway and reduce the generation of toxic metabolites. Rarely, patients have been treated with cholic acid as opposed to CDCA and have had a similar biochemical and clinical response to therapy, though the number of patients treated with cholic acid is too small to draw firm conclusions from these reports. [77]

If hypercholesterolemia is not controlled with CDCA treatment alone, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors may be added. HMG-CoA reductase inhibitors (ie, statins) have well-established efficacy and safety in patients with hypercholesterolemia and have also been used alone and in combination with CDCA to treat CTX.

Dotti et al examined treatment with CDCA, simvastatin, and low-density lipoprotein apheresis in several combinations. [74] Although the established treatments performed well, low-density lipoprotein apheresis was not associated with a clinical benefit and possibly put the patient at risk for treatment complications.

Other medical treatment modalities typically used in the treatment of disorders of bile and cholesterol metabolism, specifically hydrophilic 7 beta-hydroxy bile acids and cholestyramine, have been ineffective. [75]



Bile Acids

Class Summary

The primary treatment is CDCA, which was initially used for treatment of gallstones. In the United States, CDCA is available with the brand name Chenodal. 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 withCTX. In several studies, the bile acids and metabolites in plasma, bile, urine, and cerebrospinal fluid 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 CTX 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. [78]  Further studies have confirmed and expanded on these findings. [64]

Pharmacologic treatment may be initiated at any stage of disease, though some neurological symptoms are irreversible. [64]  Multiple studies have demonstrated that patients who started treatment later had a worse outcome than those who started treatment earlier. [79, 80]  A subset of patients continue to deteriorate despite treatment. [81]  Even late institution of treatment may lead to some clinical improvement. [82, 17, 79]  The effect of treatment on cataract progression is described in one study. [83]

Generally, CDCA appears to be well tolerated, although hepatoxicity has been reported in at least one infant. In that case, dose reduction was successful in resolving hepatotoxicity. [84]


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 individuals withCTX. [72, 77] Currently, there is insufficient evidence to recommend its routine use inCTX.

Chenodiol (Chenodal)

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