RARE DISEASE
Congenital bile acid synthesis defect type 2
Congenital bile acid synthesis defect type 2
Congenital bile acid synthesis defect type 2
Synonyms: BASD2, Cholestasis with delta(4)-3-oxosteroid 5-beta-reductase deficiency
Synonyms: BASD2, Cholestasis with delta(4)-3-oxosteroid 5-beta-reductase deficiency
Synonyms: BASD2, Cholestasis with delta(4)-3-oxosteroid 5-beta-reductase deficiency
Drug discovery
1
drug
With orphan designation
Overview
Congenital bile acid synthesis defect type 2 (CBAS2) is an autosomal recessive disorder caused by mutations in the AKR1D1 gene, leading to impaired synthesis of primary bile acids. This results in severe neonatal cholestasis, hepatosplenomegaly, steatorrhea, and fat-soluble vitamin deficiencies. Untreated, it rapidly progresses to cirrhosis and liver failure in infancy. Diagnosis relies on urine mass spectrometry to detect toxic delta(4)-3-oxo bile acid metabolites. Early oral cholic acid therapy suppresses atypical bile acid production, reverses liver damage, and prevents progression, with excellent long-term outcomes when initiated promptly [1][2][6].
Burden
100% fatality in untreated infants due to liver failure [2][6].
Lifelong therapy required; delayed diagnosis increases risks of irreversible cirrhosis, coagulopathy, and malnutrition [1][8].
Economic burden includes specialized diagnostics (genetic/urine metabolite testing) and potential transplant costs [3][8].
Therapies
First-line: Oral cholic acid replacement (10–15 mg/kg/day) to restore bile acid pool and inhibit toxic metabolite accumulation [1][6].
Alternative: Ursodeoxycholic acid (less effective, does not suppress atypical bile acid synthesis) [1].
Advanced disease: Liver transplantation if cirrhosis develops despite therapy [1][3].
Categories: rare genetic diseases, rare hepatic diseases, rare inborn errors of metabolism, rare transplant-related disorders
Research Papers
21 drug discovery papers about Congenital bile acid synthesis defect type 2, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
21 drug discovery papers about Congenital bile acid synthesis defect type 2, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2021-11-19 | Effects of S-adenosyl-L-Methionine Combined with Ursodesoxycholic Acid on Serum Endotoxin, MMP-9 and IL-18 in Neonates with Cholestasis
To compare the effect of ursodesoxycholic acid (UDCA) with S-adenosyl-L-methionine (SAMe) plus UDCA in handling of cholestasis in neonates, and their influences on serum endotoxin, matrix metalloproteinase-9 (MMP-9) and interleukin 18 (IL-18).Randomised controlled trial. Luzhou People's Hospital, China, from April 2019 to December 2020.A total of 102 neonates with cholestasis were evenly divided into control group and observation group with random double-blind. The former treated with UDCA tablets, and the latter was treated with SAMe plus UDCA. Serum endotoxin, MMP-9 and IL-18 were compared between the two groups.Total effective rate of treatment in observation group was 92.16% (47 cases), which was higher than that in control group 70.59% (36 cases) (p=0.005). Levels of serum endotoxin, MMP-9 and IL-18 in observation group were respectively 11.12 ± 1.07 pg/mL, 646.72 ± 42.56 ng/mL and 2.51 ± 0.19 pg/mL, which was lower than those in control group (p<0.001, p =0.007 and p<0.001, respectively) after 10 days of treatment.Compared with UDCA alone, SAMe plus UDCA can more effectively improve the curative effect of neonatal cholestasis, and reduce serum endotoxin, MMP-9 and IL-18 levels. Key Words: Ursodesoxycholic acid (UDCA), Neonates, Cholestasis, Endotoxin, Matrix metalloproteinase-9 (MMP-9), Interleukin 18 (IL-18).
2019-11-20 | Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives
Tauroursodeoxycholic acid (TUDCA) is a naturally occurring hydrophilic bile acid that has been used for centuries in Chinese medicine. Chemically, TUDCA is a taurine conjugate of ursodeoxycholic acid (UDCA), which in contemporary pharmacology is approved by Food and Drug Administration (FDA) for treatment of primary biliary cholangitis. Interestingly, numerous recent studies demonstrate that mechanisms of TUDCA functioning extend beyond hepatobiliary disorders. Thus, TUDCA has been demonstrated to display potential therapeutic benefits in various models of many diseases such as diabetes, obesity, and neurodegenerative diseases, mostly due to its cytoprotective effect. The mechanisms underlying this cytoprotective activity have been mainly attributed to alleviation of endoplasmic reticulum (ER) stress and stabilization of the unfolded protein response (UPR), which contributed to naming TUDCA as a chemical chaperone. Apart from that, TUDCA has also been found to reduce oxidative stress, suppress apoptosis, and decrease inflammation in many in-vitro and in-vivo models of various diseases. The latest research suggests that TUDCA can also play a role as an epigenetic modulator and act as therapeutic agent in certain types of cancer. Nevertheless, despite the massive amount of evidence demonstrating positive effects of TUDCA in pre-clinical studies, there are certain limitations restraining its wide use in patients. Here, molecular and cellular modes of action of TUDCA are described and therapeutic opportunities and limitations of this bile acid are discussed.
2017-10-26 | [Clinical feature and genetic analysis of a family affected by congenital bile acid synthesis defect type 2: identification of 2 novel mutations in AKR1D1 gene].
Congenital bile acid synthesis defect type 2 (CBAS2) is an autosomal recessive disorder caused by biallelic mutations of AKR1D1 gene, which encodes the Δ4-3-oxo-steroid 5β-reductase. Cholestatic jaundice is the main clinical manifestation, accompanied by malabsorption of fat and fat-soluble vitamins. This paper reported the clinical and genetic features of a CBAS2 patient definitely diagnosed by AKR1D1 genetic analysis. An 8-month-old male infant was referred to the hospital with the complaint of jaundiced skin and sclera over 7 months. On physical examination, growth retardation and malnutrition were discovered besides mild jaundice of the skin and sclera. The liver was palpable 8 cm below the right subcostal margin with medium texture, and the spleen was not enlarged. On liver function test, elevated levels of bilirubin (predominantly conjugated bilirubin) and transaminases were detected, but serum total bile acids and γ-glutamyl transpeptidase levels were within the normal ranges. Liver histopathologic analysis showed disorganized bile ducts, obvious multinucleated giant cells, significant cholestasis in hepatocytes, together with portal and interstitial fibrosis and lymphocytic infiltration. Via next generation sequencing analysis and Sanger sequencing confirmation, the infant proved to be a compound heterozygote of the AKR1D1 variants c.579+2delT and c.853C>T(p.Q285X), two novel mutations originated from his mother and father, respectively. CBAS2 was thus definitely diagnosed, and chenodeoxycholic acid was given orally. As a result, the abnormal liver function and hepatomegaly were improved gradually. On a follow-up 3 months later, a soft liver was palpable 2.5 cm below the right subcostal margin, and all liver function indices recovered to normal ranges. 先天性胆汁酸合成障碍2型（CBAS2）是编码Δ4-3-氧固醇5β-还原酶的AKR1D1基因突变导致的常染色体隐性遗传病，以胆汁淤积性黄疸为主要临床表现，伴脂肪和脂溶性维生素吸收障碍。本文报道了1例CBAS2患儿的临床特点及AKR1D1基因突变分析结果。患儿为8个月男婴，因发现全身皮肤、巩膜黄染7月余就诊。体查发现患儿发育、营养差；皮肤、巩膜轻度黄染；肝右肋下8 cm，质地中等，脾脏不大。血生化结果发现转氨酶和总胆红素升高，以结合胆红素升高为主，但γ-谷氨酰转肽酶和总胆汁酸水平基本正常。肝脏组织学检查见胆管排列紊乱，多核巨细胞易见，肝细胞内明显淤胆，伴间质纤维组织增生及淋巴细胞浸润。代谢性肝病组套二代测序及Sanger测序验证结果证实患儿AKR1D1基因型为c.579+2delT/c.853C > T（p.Q285X），两个突变均为新突变，且分别来源于其母亲和父亲。患儿最终确诊为CBAS2，给予鹅去氧胆酸治疗后，肝功能明显好转，肝肿大逐渐改善。3个月后随访，肝脏右肋下2.5 cm可及，质软，肝功能各项指标已恢复正常。
2017-06-21 | Oral Cholic Acid Is Efficacious and Well Tolerated in Patients With Bile Acid Synthesis and Zellweger Spectrum Disorders
Patients with bile acid synthesis disorders (BASDs) due to single enzyme defects (SEDs) or Zellweger spectrum disorders (ZSDs) accumulate hepatotoxic atypical bile acids resulting in potentially fatal progressive liver disease. We evaluated the efficacy and safety of oral cholic acid in patients with BASD.In this phase 3, open-label, single-arm, nonrandomized, noncomparative study conducted over 18 years, patients were administered cholic acid orally 10 to 15 mg · kg · day. The primary efficacy variables were changes from pre- to post-treatment in atypical urinary bile acids, liver chemistries (serum aspartate aminotransferase, alanine aminotransferase), and height and weight. Additional efficacy variables included changes in serum bilirubin and liver histology.Of the 85 enrolled patients (63 with SED and 22 with ZSD), 79 received at least 1 dose of study medication; 70 patients (50 with SED and 20 with ZSD) were included in the modified intent-to-treat dataset. Cholic acid significantly improved urine bile acid metabolite scores (P < 0.0001) and serum aspartate aminotransferase and alanine aminotransferase (P < 0.0001) in patients with SED and ZSD. Cholic acid also improved height and weight percentiles in both groups, but only the change in weight was significant (P < 0.05). Serum direct bilirubin decreased significantly post-treatment (P < 0.001) in the intent-to-treat population, and liver biopsies showed either stable findings or histologic improvement in all parameters except bridging fibrosis. The overall safety profile of cholic acid was favorable, with no study drug-related serious adverse events or drug-related deaths reported.Oral cholic acid is a safe, efficacious, and well-tolerated treatment for BASD due to SED and ZSD.
2008-08-16 | A boy with UDCA-dependent hypertransaminasemia
Introduction. About 10% of children with isolated chronic hypertransaminasemia, observed at a tertiary paediatric department, are affected by genetic disorders; in another 10% of cases no overt aetiology is identifiable (1). Ursodeoxycholic acid (UDCA) is used for cholestatic liver diseases. Here is described a 6-year-old boy, without either clinical or biochemical signs of cholestasis, in whom normalisation of liver enzymes was strictly dependent on UDCA therapy.
gene therapies
2022-05-01 | MiR-200c-3p targets SESN1 and represses the IL-6/AKT loop to prevent cholangiocyte activation and cholestatic liver fibrosis
Cholestasis causes ductular reaction in the liver where the reactive cholangiocytes not only proliferate but also gain a neuroendocrine-like phenotype, leading to inflammatory cell infiltration and extracellular matrix deposition and contributing to the development and progression of cholestatic liver fibrosis. This study aims to elucidate the role of miR-200c in cholestasis-induced biliary liver fibrosis and cholangiocyte activation. We found that miR-200c was extremely abundant in cholangiocytes but was reduced by cholestasis in a bile duct ligation (BDL) mouse model; miR-200c was also decreased by bile acids in vitro. Phenotypically, loss of miR-200c exacerbated cholestatic liver injury, including periductular fibrosis, intrahepatic inflammation, and biliary hyperplasia in both the BDL model and the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) model. We identified sestrin 1 (SESN1) as a target of miR-200c. Sesn1-/--BDL mice showed mitigation of cholestatic liver injury. On a molecular level, the pro-proliferative IL-6/AKT feedback loop was activated in Mir200c-/- livers but was inhibited in Sesn1-/- livers upon cholestasis in mice. Furthermore, rescuing expression of miR-200c by the adeno-associated virus serotype 8 ameliorated BDL-induced liver injury in Mir200c-/- mice. Taken together, this study demonstrates that miR-200c restrains the proliferative and neuroendocrine-like activation of cholangiocytes by targeting SESN1 and inhibiting the IL-6/AKT feedback loop to protect against cholestatic liver fibrosis. Our findings provide mechanistic insights regarding biliary liver fibrosis, which may help to reveal novel therapeutic targets for the treatment of cholestatic liver injury and liver fibrosis.
2013-06-01 | Diet1 Functions in the FGF15/19 Enterohepatic Signaling Axis to Modulate Bile Acid and Lipid Levels
We identified a mutation in the Diet1 gene in a mouse strain that is resistant to hyperlipidemia and atherosclerosis. Diet1 encodes a 236 kD protein consisting of tandem low-density lipoprotein receptor and MAM (meprin-A5-protein tyrosine phosphatase mu) domains and is expressed in the enterocytes of the small intestine. Diet1-deficient mice exhibited an elevated bile acid pool size and impaired feedback regulation of hepatic Cyp7a1, which encodes the rate-limiting enzyme in bile acid synthesis. In mouse intestine and in cultured human intestinal cells, Diet1 expression levels influenced the production of fibroblast growth factor 15/19 (FGF15/19), a hormone that signals from the intestine to liver to regulate Cyp7a1. Transgenic expression of Diet1, or adenoviral-mediated Fgf15 expression, restored normal Cyp7a1 regulation in Diet-1-deficient mice. Diet1 and FGF19 proteins exhibited overlapping subcellular localization in cultured intestinal cells. These results establish Diet1 as a control point in enterohepatic bile acid signaling and lipid homeostasis.
small molecules
2021-11-19 | Effects of S-adenosyl-L-Methionine Combined with Ursodesoxycholic Acid on Serum Endotoxin, MMP-9 and IL-18 in Neonates with Cholestasis
To compare the effect of ursodesoxycholic acid (UDCA) with S-adenosyl-L-methionine (SAMe) plus UDCA in handling of cholestasis in neonates, and their influences on serum endotoxin, matrix metalloproteinase-9 (MMP-9) and interleukin 18 (IL-18).Randomised controlled trial. Luzhou People's Hospital, China, from April 2019 to December 2020.A total of 102 neonates with cholestasis were evenly divided into control group and observation group with random double-blind. The former treated with UDCA tablets, and the latter was treated with SAMe plus UDCA. Serum endotoxin, MMP-9 and IL-18 were compared between the two groups.Total effective rate of treatment in observation group was 92.16% (47 cases), which was higher than that in control group 70.59% (36 cases) (p=0.005). Levels of serum endotoxin, MMP-9 and IL-18 in observation group were respectively 11.12 ± 1.07 pg/mL, 646.72 ± 42.56 ng/mL and 2.51 ± 0.19 pg/mL, which was lower than those in control group (p<0.001, p =0.007 and p<0.001, respectively) after 10 days of treatment.Compared with UDCA alone, SAMe plus UDCA can more effectively improve the curative effect of neonatal cholestasis, and reduce serum endotoxin, MMP-9 and IL-18 levels. Key Words: Ursodesoxycholic acid (UDCA), Neonates, Cholestasis, Endotoxin, Matrix metalloproteinase-9 (MMP-9), Interleukin 18 (IL-18).
2019-11-20 | Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives
Tauroursodeoxycholic acid (TUDCA) is a naturally occurring hydrophilic bile acid that has been used for centuries in Chinese medicine. Chemically, TUDCA is a taurine conjugate of ursodeoxycholic acid (UDCA), which in contemporary pharmacology is approved by Food and Drug Administration (FDA) for treatment of primary biliary cholangitis. Interestingly, numerous recent studies demonstrate that mechanisms of TUDCA functioning extend beyond hepatobiliary disorders. Thus, TUDCA has been demonstrated to display potential therapeutic benefits in various models of many diseases such as diabetes, obesity, and neurodegenerative diseases, mostly due to its cytoprotective effect. The mechanisms underlying this cytoprotective activity have been mainly attributed to alleviation of endoplasmic reticulum (ER) stress and stabilization of the unfolded protein response (UPR), which contributed to naming TUDCA as a chemical chaperone. Apart from that, TUDCA has also been found to reduce oxidative stress, suppress apoptosis, and decrease inflammation in many in-vitro and in-vivo models of various diseases. The latest research suggests that TUDCA can also play a role as an epigenetic modulator and act as therapeutic agent in certain types of cancer. Nevertheless, despite the massive amount of evidence demonstrating positive effects of TUDCA in pre-clinical studies, there are certain limitations restraining its wide use in patients. Here, molecular and cellular modes of action of TUDCA are described and therapeutic opportunities and limitations of this bile acid are discussed.
2017-10-26 | [Clinical feature and genetic analysis of a family affected by congenital bile acid synthesis defect type 2: identification of 2 novel mutations in AKR1D1 gene].
Congenital bile acid synthesis defect type 2 (CBAS2) is an autosomal recessive disorder caused by biallelic mutations of AKR1D1 gene, which encodes the Δ4-3-oxo-steroid 5β-reductase. Cholestatic jaundice is the main clinical manifestation, accompanied by malabsorption of fat and fat-soluble vitamins. This paper reported the clinical and genetic features of a CBAS2 patient definitely diagnosed by AKR1D1 genetic analysis. An 8-month-old male infant was referred to the hospital with the complaint of jaundiced skin and sclera over 7 months. On physical examination, growth retardation and malnutrition were discovered besides mild jaundice of the skin and sclera. The liver was palpable 8 cm below the right subcostal margin with medium texture, and the spleen was not enlarged. On liver function test, elevated levels of bilirubin (predominantly conjugated bilirubin) and transaminases were detected, but serum total bile acids and γ-glutamyl transpeptidase levels were within the normal ranges. Liver histopathologic analysis showed disorganized bile ducts, obvious multinucleated giant cells, significant cholestasis in hepatocytes, together with portal and interstitial fibrosis and lymphocytic infiltration. Via next generation sequencing analysis and Sanger sequencing confirmation, the infant proved to be a compound heterozygote of the AKR1D1 variants c.579+2delT and c.853C>T(p.Q285X), two novel mutations originated from his mother and father, respectively. CBAS2 was thus definitely diagnosed, and chenodeoxycholic acid was given orally. As a result, the abnormal liver function and hepatomegaly were improved gradually. On a follow-up 3 months later, a soft liver was palpable 2.5 cm below the right subcostal margin, and all liver function indices recovered to normal ranges. 先天性胆汁酸合成障碍2型（CBAS2）是编码Δ4-3-氧固醇5β-还原酶的AKR1D1基因突变导致的常染色体隐性遗传病，以胆汁淤积性黄疸为主要临床表现，伴脂肪和脂溶性维生素吸收障碍。本文报道了1例CBAS2患儿的临床特点及AKR1D1基因突变分析结果。患儿为8个月男婴，因发现全身皮肤、巩膜黄染7月余就诊。体查发现患儿发育、营养差；皮肤、巩膜轻度黄染；肝右肋下8 cm，质地中等，脾脏不大。血生化结果发现转氨酶和总胆红素升高，以结合胆红素升高为主，但γ-谷氨酰转肽酶和总胆汁酸水平基本正常。肝脏组织学检查见胆管排列紊乱，多核巨细胞易见，肝细胞内明显淤胆，伴间质纤维组织增生及淋巴细胞浸润。代谢性肝病组套二代测序及Sanger测序验证结果证实患儿AKR1D1基因型为c.579+2delT/c.853C > T（p.Q285X），两个突变均为新突变，且分别来源于其母亲和父亲。患儿最终确诊为CBAS2，给予鹅去氧胆酸治疗后，肝功能明显好转，肝肿大逐渐改善。3个月后随访，肝脏右肋下2.5 cm可及，质软，肝功能各项指标已恢复正常。
2017-06-21 | Oral Cholic Acid Is Efficacious and Well Tolerated in Patients With Bile Acid Synthesis and Zellweger Spectrum Disorders
Patients with bile acid synthesis disorders (BASDs) due to single enzyme defects (SEDs) or Zellweger spectrum disorders (ZSDs) accumulate hepatotoxic atypical bile acids resulting in potentially fatal progressive liver disease. We evaluated the efficacy and safety of oral cholic acid in patients with BASD.In this phase 3, open-label, single-arm, nonrandomized, noncomparative study conducted over 18 years, patients were administered cholic acid orally 10 to 15 mg · kg · day. The primary efficacy variables were changes from pre- to post-treatment in atypical urinary bile acids, liver chemistries (serum aspartate aminotransferase, alanine aminotransferase), and height and weight. Additional efficacy variables included changes in serum bilirubin and liver histology.Of the 85 enrolled patients (63 with SED and 22 with ZSD), 79 received at least 1 dose of study medication; 70 patients (50 with SED and 20 with ZSD) were included in the modified intent-to-treat dataset. Cholic acid significantly improved urine bile acid metabolite scores (P < 0.0001) and serum aspartate aminotransferase and alanine aminotransferase (P < 0.0001) in patients with SED and ZSD. Cholic acid also improved height and weight percentiles in both groups, but only the change in weight was significant (P < 0.05). Serum direct bilirubin decreased significantly post-treatment (P < 0.001) in the intent-to-treat population, and liver biopsies showed either stable findings or histologic improvement in all parameters except bridging fibrosis. The overall safety profile of cholic acid was favorable, with no study drug-related serious adverse events or drug-related deaths reported.Oral cholic acid is a safe, efficacious, and well-tolerated treatment for BASD due to SED and ZSD.
2008-08-16 | A boy with UDCA-dependent hypertransaminasemia
Introduction. About 10% of children with isolated chronic hypertransaminasemia, observed at a tertiary paediatric department, are affected by genetic disorders; in another 10% of cases no overt aetiology is identifiable (1). Ursodeoxycholic acid (UDCA) is used for cholestatic liver diseases. Here is described a 6-year-old boy, without either clinical or biochemical signs of cholestasis, in whom normalisation of liver enzymes was strictly dependent on UDCA therapy.
gene therapies
2022-05-01 | MiR-200c-3p targets SESN1 and represses the IL-6/AKT loop to prevent cholangiocyte activation and cholestatic liver fibrosis
Cholestasis causes ductular reaction in the liver where the reactive cholangiocytes not only proliferate but also gain a neuroendocrine-like phenotype, leading to inflammatory cell infiltration and extracellular matrix deposition and contributing to the development and progression of cholestatic liver fibrosis. This study aims to elucidate the role of miR-200c in cholestasis-induced biliary liver fibrosis and cholangiocyte activation. We found that miR-200c was extremely abundant in cholangiocytes but was reduced by cholestasis in a bile duct ligation (BDL) mouse model; miR-200c was also decreased by bile acids in vitro. Phenotypically, loss of miR-200c exacerbated cholestatic liver injury, including periductular fibrosis, intrahepatic inflammation, and biliary hyperplasia in both the BDL model and the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) model. We identified sestrin 1 (SESN1) as a target of miR-200c. Sesn1-/--BDL mice showed mitigation of cholestatic liver injury. On a molecular level, the pro-proliferative IL-6/AKT feedback loop was activated in Mir200c-/- livers but was inhibited in Sesn1-/- livers upon cholestasis in mice. Furthermore, rescuing expression of miR-200c by the adeno-associated virus serotype 8 ameliorated BDL-induced liver injury in Mir200c-/- mice. Taken together, this study demonstrates that miR-200c restrains the proliferative and neuroendocrine-like activation of cholangiocytes by targeting SESN1 and inhibiting the IL-6/AKT feedback loop to protect against cholestatic liver fibrosis. Our findings provide mechanistic insights regarding biliary liver fibrosis, which may help to reveal novel therapeutic targets for the treatment of cholestatic liver injury and liver fibrosis.
2013-06-01 | Diet1 Functions in the FGF15/19 Enterohepatic Signaling Axis to Modulate Bile Acid and Lipid Levels
We identified a mutation in the Diet1 gene in a mouse strain that is resistant to hyperlipidemia and atherosclerosis. Diet1 encodes a 236 kD protein consisting of tandem low-density lipoprotein receptor and MAM (meprin-A5-protein tyrosine phosphatase mu) domains and is expressed in the enterocytes of the small intestine. Diet1-deficient mice exhibited an elevated bile acid pool size and impaired feedback regulation of hepatic Cyp7a1, which encodes the rate-limiting enzyme in bile acid synthesis. In mouse intestine and in cultured human intestinal cells, Diet1 expression levels influenced the production of fibroblast growth factor 15/19 (FGF15/19), a hormone that signals from the intestine to liver to regulate Cyp7a1. Transgenic expression of Diet1, or adenoviral-mediated Fgf15 expression, restored normal Cyp7a1 regulation in Diet-1-deficient mice. Diet1 and FGF19 proteins exhibited overlapping subcellular localization in cultured intestinal cells. These results establish Diet1 as a control point in enterohepatic bile acid signaling and lipid homeostasis.
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Drug Discovery Landscape
1 orphan drug designation for Congenital bile acid synthesis defect type 2.
1 orphan drug designation for Congenital bile acid synthesis defect type 2.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Cholic acid [Kolbam] | small molecules | EMA | [INACTIVE] Avena Therapeutics Limited |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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