scholarly journals Pharmacy Compounded Medicines for Patients With Rare Diseases: Lessons Learned From Chenodeoxycholic Acid and Cholic Acid

2021 ◽  
Vol 12 ◽  
Author(s):  
Yasmin Polak ◽  
Bart A. W. Jacobs ◽  
E. Marleen Kemper
Keyword(s):  
Cholic Acid ◽  
Rare Diseases ◽  
Chenodeoxycholic Acid ◽  
Large Population ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Lessons Learned ◽  
Safe Alternative ◽  
Vulnerable Patients ◽  
Practical Guidelines

Patients with rare diseases are often confronted with the fact that effective medicines are unavailable or simply not being developed. This situation jeopardizes the health of a large population of vulnerable patients with rare diseases. Pharmacy compounded formulations can provide a safe alternative when authorized treatments are unavailable or unsuitable. Practical guidelines on how to develop and implement pharmacy compounded formulations for patients with rare diseases are limited. The aim of this article is to provide guidance for when and how to apply pharmacy compounded formulations for patients with rare diseases. This is illustrated with two challenging examples: the development and implementation of pharmacy compounding of 1) chenodeoxycholic acid (CDCA) capsules for patients with cerebrotendinous xanthomatosis (CTX) and 2) cholic acid (CA) capsules for patients with rare bile acid synthesis defects (BASD). All critical steps of the development of CDCA and CA capsules are explained and summarized in a practical guideline.

scholarly journals Cerebrotendinous Xanthomatosis: diversity of presentation and refining treatment with chenodeoxycholic acid

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Mahjabin Islam ◽  
Nigel Hoggard ◽  
Marios Hadjivassiliou
Keyword(s):  
Chenodeoxycholic Acid ◽  
Clinical Characteristics ◽  
Spastic Paraparesis ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Cerebrotendinous Xanthomatosis ◽  
Juvenile Onset ◽  
Progressive Ataxia ◽  
Classical Triad ◽  
High Index Of Suspicion

Abstract Background Cerebrotendinous xanthomatosis (CTX) is a rare but treatable neurometabolic disorder of lipid storage and bile acid synthesis. Whilst CTX is said to present with the classic triad of juvenile onset cataracts, tendon xanthomata and progressive ataxia, the diversity of presentation can be such that the diagnosis may be substantially delayed resulting in permanent neurological disability. Methods A retrospective review of the clinical characteristics and imaging findings of 4 patients with CTX presenting to the Sheffield Ataxia Centre over a period of 25 years. Results Although CTX-related symptoms were present from childhood, the median age at diagnosis was 39 years. Only 1 of the 4 cases had tendon xanthomata, only 2 cases had juvenile onset cataracts and 3 had progressive ataxia with one patient presenting with spastic paraparesis. Serum cholestanol was elevated in all 4 patients, proving to be a reliable diagnostic tool. In addition, cholestanol was raised in the CSF of 2 patients who underwent lumbar puncture. Despite treatment with chenodeoxycholic acid (CDCA) and normalization of serum cholestanol, CSF cholestanol remained high in one patient, necessitating increase in the dose of CDCA. Further adjustments to the dose of CDCA in the patient with raised CSF cholestanol resulted in slowing of progression. Two of the patients who have had the disease for the longest continued to progress, one subsequently dying from pneumonia. Conclusion A high index of suspicion for CTX, even in the absence of the classical triad is essential in reaching such diagnosis. The earlier the diagnosis and treatment, the better the outcome.

scholarly journals Bile Acid Synthesis Disorders in Japan: Long-Term Outcome and Chenodeoxycholic Acid Treatment

2021 ◽  
Author(s):  
Akihiko Kimura ◽  
Tatsuki Mizuochi ◽  
Hajime Takei ◽  
Akira Ohtake ◽  
Jun Mori ◽  
...  
Keyword(s):  
Bile Acid ◽  
Chenodeoxycholic Acid ◽  
Acid Treatment ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Term Outcome ◽  
Long Term Outcome

scholarly journals Cholic acid for primary bile acid synthesis defects: a life-saving therapy allowing a favorable outcome in adulthood

2018 ◽  
Vol 13 (1) ◽  
Author(s):  
Emmanuel Gonzales ◽  
Lorenza Matarazzo ◽  
Stéphanie Franchi-Abella ◽  
Alain Dabadie ◽  
Joseph Cohen ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Favorable Outcome ◽  
Life Saving ◽  
Primary Bile Acid

scholarly journals Atypical clinical presentation and successful treatment with oral cholic acid of a child with defective bile acid synthesis due to a novel mutation in the HSD3B7 gene

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Grazia Bossi ◽  
Giuseppe Giordano ◽  
Gaetana Anna Rispoli ◽  
Giuseppe Maggiore ◽  
Mauro Naturale ◽  
...  
Keyword(s):  
Bile Acid ◽  
Replacement Therapy ◽  
Cholic Acid ◽  
Novel Mutation ◽  
Failure To Thrive ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Ionization Mass ◽  
Fast Atom Bombardment Ionization ◽  
Atypical Clinical Presentation

We report definitive diagnosis and effective treatment with oral cholic acid in one Italian male child affected by 3β- hydroxy-Δ5-C27-steroid dehydrogenase (3β- HSD) deficiency. He presented with failure to thrive, hepatomegaly and multiple cystic images in kidneys; no biochemical evidence of cholestasis. Large amounts of bile acid metabolites was detected in urine by fast atom bombardment ionization mass spectrometry (FAB-MS). <em>HSDH3B7</em> gene analysis identified one mutation in intron 4, at nucleotide 432, G&gt;A substitution that has never been reported before.The replacement therapy with oral cholic acid started early after the diagnosis and is still ongoing. Three years later hepatomegaly is no longer evident, liver function is normal and the child is growing regularly. In our experience, clinical features of 3β-HSD deficiency can be very poor and even cholestasis can lack at diagnosis. Early replacement therapy with cholic acid is safe and leads to clinical and biochemical control of the disease.

scholarly journals Cholic acid mediates negative feedback regulation of bile acid synthesis in mice

2002 ◽  
Vol 110 (8) ◽  
pp. 1191-1200 ◽  
Author(s):  
Jia Li-Hawkins ◽  
Mats Gåfvels ◽  
Maria Olin ◽  
Erik G. Lund ◽  
Ulla Andersson ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Negative Feedback ◽  
Feedback Regulation ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Negative Feedback Regulation

scholarly journals Nuclear and cytosolic distribution of conjugated cholic acid and radiolabelled glycocholic acid in rat liver

1979 ◽  
Vol 178 (1) ◽  
pp. 71-78 ◽  
Author(s):  
R C Strange ◽  
G J Beckett ◽  
I W Percy-Robb
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Rat Liver ◽  
Superior Mesenteric Vein ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Acid Receptor ◽  
Glycocholic Acid ◽  
Bile Acid Receptor

1. Normally fed and cholestyramine-treated rats were injected through the superior mesenteric vein with different amounts of radiolabelled glycoholic acid and the appearance of radioactivity in bile was measured. 2. In normally fed rats radioactivity appeared in bile within 30 s of injection and reached a maximum after 2 1/2 min; in the cholestyramine-treated animals the appearance of radioactivity was slower and less of the injected material was excreted into bile. 3. At 10 min after injection, livers were removed and the amounts of radioactive glycoholic acid and endogenous cholic acid conjugates in nuclei and cytosol were determined; most of the bile acid was found in the cytosol, only small amounts being found in nuclei. 4. Nuclear preparations from both normally fed and cholestyramine-fed rats were extracted with KCl (0.4 M) in an attempt to identify a putative bile acid receptor, but no such receptor was found. 5. Regulation of bile acid synthesis does not involve nuclear binding of bile acids.

Oral Cholic Acid for Hereditary Defects of Primary Bile Acid Synthesis: A Safe and Effective Long-term Therapy

2009 ◽  
Vol 137 (4) ◽  
pp. 1310-1320.e3 ◽  
Author(s):  
Emmanuel Gonzales ◽  
Marie F. Gerhardt ◽  
Monique Fabre ◽  
Kenneth D.R. Setchell ◽  
Anne Davit–Spraul ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Term Therapy ◽  
Long Term Therapy ◽  
Primary Bile Acid
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