Drug Screen Identifies Leflunomide for Treatment of Inflammatory Bowel Diseases Caused by TTC7A Deficiency

Mutations in the tetratricopeptide repeat domain 7A gene (TTC7A) cause intestinal epithelial and immune defects. Patients can become immune deficient and develop apoptotic enterocolitis, multiple intestinal atresia, and recurrent intestinal stenosis. The intestinal disease in patients with TTC7A deficiency is severe, untreatable, and recurs despite resection or allogeneic hematopoietic stem cell transplant. We screened drugs for those that prevent apoptosis of in cells with TTC7A deficiency and tested their effects in an animal model of the disease.
Source: Gastroenterology - Category: Gastroenterology Authors: Source Type: research

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Publication date: Available online 14 December 2019Source: Chemico-Biological InteractionsAuthor(s): Ryan N. Serio, Lorraine J. GudasAbstractEthanol (EtOH) is a recreationally ingested compound that is both teratogenic and carcinogenic in humans. Because of its abundant consumption worldwide and the vital role of stem cells in the formation of birth defects and cancers, delineating the effects of EtOH on stem cell function is currently an active and urgent pursuit of scientific investigation to explicate some of the mechanisms contributing to EtOH toxicity. Stem cells represent a primordial, undifferentiated phase of devel...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research
Authors: Escudero-Hernández C, Bernardo D, Arranz E, Garrote JA Abstract Celiac disease (CeD) and inflammatory bowel disease (IBD) are chronic gastrointestinal disorders of inflammatory origin that develop in response to environmental triggers in genetically predisposed individuals. CeD localizes in the duodenal mucosa, where intolerance develops to dietary gluten from wheat, barley, rye, and some varieties of oats. IBD, in turn, is subdivided primarily into Crohn's disease (CD) and colitis, with ulcerative colitis (UC) being the most thoroughly investigated form. PMID: 31830796 [PubMed - as supplied by publisher]
Source: Revista Espanola de Enfermedades Digestivas - Category: Gastroenterology Tags: Rev Esp Enferm Dig Source Type: research
CONCLUSIONS: the frequency of complicated acute diverticulitis is higher in immunodeficient patients than that of the general population. Non-surgical treatment seems to be as safe as in immunocompetent patients. Younger and transplanted patients were higher risk groups for severe acute diverticulitis that required a more aggressive management initially. PMID: 31830795 [PubMed - as supplied by publisher]
Source: Revista Espanola de Enfermedades Digestivas - Category: Gastroenterology Tags: Rev Esp Enferm Dig Source Type: research
CONCLUSIONS: The use of this novel cartilage restoration surgical technique provides excellent clinical, functional, and MRI-based outcomes in young, active individuals with full-thickness cartilage or osteochondral defects. LEVEL OF EVIDENCE: Level IV-Therapeutic case series. PMID: 31835970 [PubMed - in process]
Source: Journal of Orthopaedic Surgery - Category: Orthopaedics Authors: Tags: J Orthop Surg (Hong Kong) Source Type: research
This study lists the various anomalies on the basis of 504 references selected from a PubMed search in October 2018. RESULTS: The anomalies are grouped into three categories: anatomical anomalies: duodenal atresia and stenosis (3.9%), duodenal web and annular pancreas; aberrant right subclavian artery (12% of children with DS with cardiac anomaly); Hirschsprung's disease (2.76%); anorectal malformation (1.16%); congenital vascular malformations of the liver; orofacial cleft, bifid uvula (4.63%), and submucous orofacial cleft; esophageal atresia (0.5-0.9%); pyloric stenosis (0.3%); diaphragmatic hernia; malrotation of ...
Source: Archives de Pediatrie - Category: Pediatrics Authors: Tags: Arch Pediatr Source Type: research
Mutations in the tetratricopeptide repeat domain 7A (TTC7A) gene cause very early onset inflammatory bowel diseases (VOIBD) or multiple intestinal atresia associated with immune deficiency of various severities, ranging from combined immune deficiency to mild lymphopenia. In this manuscript, we report the clinical, biological and molecular features of a patient born from consanguineous parents, presenting with recurrent lymphoproliferative syndrome and pan-hypergammaglobulinemia associated with chronic intestinal pseudo obstruction (CIPO). Genetic screening revealed the novel c.974G>A (p.R325Q) mutation in homozygosity ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Abstract TTC7A mutations cause multiple neonatal intestinal atresias with early inflammatory bowel disease and severe combined immunodeficiency. There are no treatment protocols for this rare disease. Two new cases are described for which radical early treatment measures - total enterectomy, home parenteral nutrition, immunoglobulin therapy and intravenous antibiotic prophylaxis - have allowed both patients to develop optimally. PMID: 29921470 [PubMed - as supplied by publisher]
Source: Archives de Pediatrie - Category: Pediatrics Authors: Tags: Arch Pediatr Source Type: research
Discussion Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane receptor (CFTR). It is found in the epithelium of the bronchi, intestine, pancreatic duct and biliary tree. It regulates chloride, bicarbonate and water secretion. The heterozygous state helps prevent against secretory diarrhea, but the homozygous state causes thickened secretions in the hollow tubes of the lungs and digestive tract. There are multiple mutations (> 2000) which have been currently classified into classes depending on their protein production and activity. CF patients generally are l...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Abstract Tricho-hepato-enteric syndrome (SD/THE) and Multiple intestinal atresia with combined immune deficiency (MIA-CID) are autosomal recessive disorders that present immunological and gastrointestinal features. There are two different phenotypes of patients with TTC7A mutations: the severe form, caused by null mutations and leading to the classical MIA-CID; and the mild form, caused by missense mutations and leading to predominant features of VEO-IBD, less severe immunological involvement and hair abnormalities. We expand the knowledge about TTC7A deficiency, describing a patient with the mild phenotype of TTC...
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research
A 34-year-old man who received a liver transplant 29 years ago was incidentally found to have a 6.5-cm asymptomatic aortic root aneurysm with mild aortic insufficiency. Given the aneurysm size, a valve-sparing aortic root replacement was recommended. The patient's medical history included congestive heart failure, chronic renal failure, biliary atresia, Crohn's disease, and chronic minocycline use for acne.
Source: The Journal of Thoracic and Cardiovascular Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: Cardiothoracic imaging Source Type: research
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