Comorbidities in this study included malignant hypertension (30%), TMA with a history of transplant (23%), TMA associated with pregnancy (21%), glomerulopathy (17%), systemic disease such as systemic lupus erythematosus (SLE) or progressive systemic sclerosis (PSS) (6%), and malignancy (1%). The presence of mutations in complement regulatory proteins, or of disease-associated variations in the genes encoding these proteins (i.e., in most patients with comorbid conditions as well as in patients with aHUS as a single disease), suggests that deviations from the normal genetic coding of these factors could result in a genetic predisposition to TMA. Individuals so predisposed could have aHUS episodes precipitated by one of the known disease triggers (e.g., infection, pregnancy, surgery, trauma) as well as by other systemic diseases (e.g., malignant hypertension, SLE, cancer). Mechanisms
In healthy individuals, complement is used to attack foreign substances, and the complement system is highly regulated to prevent it from damaging healthy tissues and organs. However, in most patients with aHUS, it has been demonstrated that chronic, uncontrolled, and excessive activation of complement can result from production of anti-factor H autoantibodies or from genetic mutations in any of several complement regulatory proteins (e.g., factor H, factor HR1 or HR3, membrane cofactor protein, factor I, factor B, complement C3, and thrombomodulin). This results in platelet activation, damage to endothelial cells (cells that line the blood vessels), and white blood cell activation, leading to systemic TMA, which manifests as decreased platelet count, hemolysis (breakdown of red blood cells), damage to multiple organs, and often, death.
Gelesis100, sold under the brand name Plenity, is an oral hydrogel used to treat overweight and obesity. It absorbs water and expands in the stomach and small bowel thereby increasing feelings of fullness. Possible side effects include primarily gastrointestinal symptoms, such as diarrhea, abdominal distention, infrequent bowel movements, constipation, abdominal pain, and flatulence. It is contraindicated in pregnancy, chronic malabsorption syndromes, and cholestasis. The US Food and Drug Administration approved it in 2019 as a medical device. Gelesis100 was developed by the company Gelesis. History
The US Food and Drug Administration approved the use of Gelesis100 in April 2019 as a medical device. Gelesis100 is the first treatment of its kind for overweight and obesity. Uses
Gelesis100 is used to treat obesity and overweight. Gelesis100 is taken as a pill before meals and with water. Mechanism and physiology
Gelesis100 is an oral superabsorbent hydrogel, which is produced from carboxymethylcellulose and citric acid. The cross-linked product forms a hydrophilic matrix, which absorbs water. Taken in capsule form by mouth, as Gelesis100 absorbs water, it expands in the stomach and small intestine. After absorbing water, a semisolid gel structure forms, which may promote satiety and result in weight loss. Contraindications
Gelesis100 is contraindicated in pregnancy, chronic malabsorption syndromes, and cholestasis. Side effects
Side effects consist of minor gastrointestinal symptoms, including diarrhea, abdominal distention, infrequent bowel movements, constipation, abdominal pain, and flatulence. Gelesis100 is not associated with any severe adverse events. However, long-term safety data beyond 24 weeks is not available. References
External links
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