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Cholic acid as a treatment for cerebrotendinous xanthomatosis in adults

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Abstract

Cerebrotendineous xanthomatosis (CTX) is an autosomal recessive disorder of bile acids synthesis. Patients may present with a variety of clinical manifestations: bilateral cataract and chronic diarrhea during childhood, then occurrence of neurological debilitating symptoms in adulthood (cognitive decline, motor disorders). Plasma cholestanol is used as a diagnostic marker of CTX, and to monitor the response to the treatment. Current treatment for CTX is chenodeoxycholic acid (CDCA), which was reported to improve and/or stabilize clinical status and decrease levels of plasma cholestanol. Rare published reports have also suggested a potential efficacy of cholic acid (CA) in patients with CTX. In this retrospective Franco-Belgian multicentric study, we collected data from 12 patients treated with CA, evaluating their clinical status, cholestanol levels and adverse effects during the treatment period. The population was divided in two subgroups: treatment-naive (who never had CDCA prior to CA) and non-treatment-naive patients (who had CDCA prior to CA introduction). We found that treatment with CA significantly and strongly reduced cholestanol levels in all patients. Additionally, 10 out of 12 patients clinically improved or stabilized with CA treatment. Worsening was noted in one treatment-naïve patient and one non-treatment-naïve patient, but both patients experienced similar outcomes with CDCA treatment as well. No adverse effects were reported from patients with CA treatment, whereas elevated transaminases were observed in some patients while they were treated with CDCA. In conclusion, these findings suggest that CA may be a suitable alternative treatment for CTX, especially in patients with side effects related to CDCA.

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Acknowledgements

We thank Cécile Sourdon for her involvement to this research.

Funding

This work was supported by a Grant from Retrophin Company.

Author information

Authors and Affiliations

  1. Neurology Department, Reference Center for Lysosomal Diseases, Neurogenetics and Metabolism Unit, Hôpital Pitié-Salpêtrière, 47–83 boulevard de l’Hôpital, 75013, Paris, France

    Daniele Mandia, Heloise Pierdet & Yann Nadjar

  2. Service de Génétique Médicale, Centre de Référence des Maladies Mitochondriales, Hôpital de l’Archet 2, 151 Route de Saint-Antoine de Ginestière, B.P.3079, 06202, Nice Cedex 3, France

    Annabelle Chaussenot

  3. Unité Neurologie générale, Pôle Psychiatrie, Neurologie et Rééducation Neurologique, Service de Neurologie, CHU de Grenoble site Nord-Hôpital Albert Michallon, boulevard de la Chantourne, CS10217, 38043, Grenoble Cedex 9, France

    Gérard Besson

  4. UF Biochimie des maladies neurométaboliques-Département de Biochimie métabolique, Hôpital Pitié-Salpêtrière, 47-83 boulevard de l’Hôpital, 75013, Paris, France

    Foudil Lamari

  5. Neurological Department, Centre hospitalo-universitaire Caremeau, place du Professeur Debré, 30029, Nîmes Cedex, France

    Giovanni Castelnovo

  6. Department of Neurology, Toulouse University Hospital, 31059, Toulouse, France

    Jonathan Curot

  7. Centre de Recherche Cerveau et Cognition, CNRS, UMR5549, 31052, Toulouse, France

    Jonathan Curot

  8. Department of Neurology (Nerve-Muscle Unit), CHU Bordeaux (Pellegrin Hospital), 33076, Bordeaux, France

    Fanny Duval

  9. Inserm, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Sorbonne Université, Paris, France

    Philippe Giral

  10. Department of Endocrinology-Metabolism, AP-HP, Hôpital de la Pitié, Paris, France

    Philippe Giral

  11. Service de Nutrition & Activité Physique, Institut Pasteur de Lille, 1, rue du professeur Calmette, 59019, Lille, France

    Jean-Michel Lecerf

  12. Service de Médecine Interne, Hôpital Claude Huriez-CHRU de Lille, 59037, Lille, France

    Jean-Michel Lecerf

  13. Institut de Pathologie et de Génétique ASBL, Centre Agréé des Maladies Héréditaires du Métabolisme, Centre de Génétique Humaine, Avenue Georges Lemaitre, 25, 6041, Gosselies, Belgium

    Dominique Roland

  14. Endocrinology and Metabolism Department, Lille University Hospital, C. Huriez Hospital, 1, rue Polonovski, 59037, Lille Cedex, France

    Claire Douillard

Authors
  1. Daniele Mandia
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  2. Annabelle Chaussenot
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  3. Gérard Besson
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  4. Foudil Lamari
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  5. Giovanni Castelnovo
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  6. Jonathan Curot
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  7. Fanny Duval
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  8. Philippe Giral
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  9. Jean-Michel Lecerf
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  10. Dominique Roland
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  11. Heloise Pierdet
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  12. Claire Douillard
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  13. Yann Nadjar
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Corresponding author

Correspondence to Yann Nadjar.

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Conflicts of interest

YN: honorarium for speeches from Amicus, Actelion, Orphan Europe, Grants for research from Actelion, Leadiant Pharmaceuticals.

Ethical approval

This study has been approved by the appropriate ethics committee.

Informed consent

All patients gave their informed consent prior to their inclusion in the study.

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Mandia, D., Chaussenot, A., Besson, G. et al. Cholic acid as a treatment for cerebrotendinous xanthomatosis in adults. J Neurol 266, 2043–2050 (2019). https://doi.org/10.1007/s00415-019-09377-y

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  • DOI: https://doi.org/10.1007/s00415-019-09377-y

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