TREATMENT OF CEREBROTENDINOUS XANTHOMATOSIS - EFFECTS OF CHENODEOXYCHOLIC ACID, PRAVASTATIN, AND COMBINED USE

Treatments by oral administration of chenodeoxycholic acid (CDCA) alon e, 3-hydroxy-3-methylglutaryl (HMG) CoA reductase inhibitor (pravastat in) alone, and combination of the two drugs were attempted for 7 patie nts with cerebrotendinous xanthomatosis (CTX). CDCA treatment at a dos e of 300 mg/day reduced serum cholestanol (67.3% reduction), lathoster ol (50.8%), campesterol (61.7%) and sitosterol (12.7%). However, the s era of the patients changed to be ''atherogenic''; total cholesterol, triglyceride and low-density lipoprotein (LDL)-cholesterol were increa sed, while high-density lipoprotein (HDL)cholesterol was decreased. Co ntrarily, pravastatin at a dose of 10 mg/day improved the sera of the patients to be markedly ''anti-atherogenic'', but the reductions of ch olestanol (30.4%), lathosterol (44.0%), campesterol (22.9%) and sitost erol (9.6%) were inadequate. Combined treatment with CDCA and pravasta tin showed good overlapping of the effects of each drug alone. The ser a of the patients were apparently more ''anti-atherogenic'' than those after CDCA treatment. Serum cholestanol concentration was still 2.7 t imes higher than in controls, but the serum lathosterol level was with in the normal range, indicating that the enhancement of overall choles terol synthesis in the patients was sufficiently suppressed. Plant ste rol levels were also within the normal range. The combination of CDCA and pravastatin was a good treatment for CTX, based on the improvement of serum lipoprotein metabolism, the suppression of cholesterol synth esis, and reductions of cholestanol and plant sterol levels. In all of 7 patients, the progression of disease was arrested, but dramatic eff ects on clinical manifestations, xanthoma, and electrophysiological fi ndings could not be found after the treatment of these drugs.