Research Article Details
| Article ID: | A03281 |
| PMID: | 34062584 |
| Source: | Dtsch Med Wochenschr |
| Title: | [Alpha-1 antitrypsin deficiency: cause and cofactor for liver disease]. |
| Abstract: | Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder arising due to mutation in alpha1-antitrypsin (AAT). AAT mutations interfere with the AAT production/secretion, cause decreased AAT serum levels and accumulation of AAT in the liver. The excess AAT leads to a proteotoxic liver disease, while the lack of AAT in systemic circulation predisposes to lung injury. While AATD related lung disease is well understood, liver disease needs further awareness. Non-invasive liver stiffness measurement constitutes a useful method to estimate the extent of liver fibrosis. Significant liver fibrosis occurs in 20-35 % of individuals with the classic, severe genotype Pi*ZZ. Genotype Pi*SZ, also known as the compound heterozygous form, confers an increased risk of both liver fibrosis and liver neoplasia. Even the heterozygous genotype Pi*MZ increases the odds of fibrosis in presence of further risk factors such as obesity, male sex, metabolic syndrome and diabetes mellitus. In individuals with non-alcoholic fatty liver disease or alcohol misuse it promotes the development of liver cirrhosis. While no drug treatment exists for AATD-related liver disease, there are several compounds in clinical phase II/III-trials. These either silence the AAT production via siRNA or facilitate the secretion of AAT from the liver due to an improved folding. |
| DOI: | 10.1055/a-1277-9066 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D589 | Minor allele-specific small interfering RNA | Miscellany | -- | PNPLA3-rs738409 (I148M) variant inhibitor | -- | Under investigation | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |