Gelesis hydrogel slowed the progression of fatty liver disease even with persistent damaging effects of chronic high fat diet
Therapies exploiting the gut liver axis may offer a unique treatment option for metabolic liver disorders
Boston, November 13, 2020 – Gelesis, a biotechnology company developing a novel hydrogel platform technology to treat obesity and other chronic metabolic diseases, released today a poster presentation on the therapeutic findings of its Gel-B (GS300) at The Liver Meeting, the American Association for the Study of Liver Disease’s (AASLD) annual conference.
Gel-B (a prototype of GS300) is Gelesis’ superabsorbent hydrogel that uses crosslinked citric acid and modified cellulose and is orally administered. Previous animal data showed that Gel-B, when administered preventatively in conjunction with a high fat diet (HFD), reduced weight gain, prevented hepatic steatosis, and improved gut barrier function. This new pre-clinical study highlights that Gel-B may also have therapeutic benefits in mice fed a high fat diet.
“These pre-clinical data add to the growing body of evidence supporting the effect of orally administered hydrogel acting as a topical therapy for the intestinal wall to prevent and reverse the damage induced by a westernized diet,” said Maria Rescigno, PhD, professor at Humanitas Research Hospital in Milan and one of the study’s lead investigators. “Many of the treatment options currently available do not address the gut, and they are pharmacological and many come with potential tolerability and safety issues. These data suggest that Gel-B may offer a non-pharmacological alternative and new approach to potentially treat fatty liver disease.”
Chronic consumption of high fat diet can cause disruption of the gut barrier, leading to metabolic dysfunction and systemic inflammation. Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and is the most common form of chronic liver disease in the United States, affecting about one-quarter of the population. Some individuals with NAFLD can develop nonalcoholic steatohepatitis (NASH), an aggressive form of fatty liver disease, which is marked by liver inflammation and may progress to advanced scarring (cirrhosis) and liver failure.
In Poster Presentation (EP-16730), Gelesis hydrogel reverses high fat diet-induced intestinal alterations and slows progression of hepatic steatosis in DIO mice, hepatic steatosis was induced by feeding mice HFD (45%) for 12 weeks prior to treatment allocation. Between weeks 12 and 24, mice were treated with either HFD alone (n=20), HFD + Gel-B 2% (n=18), or HFD + Gel-B 4% (n=18). A control group (n=21) was fed chow alone for the entire experiment. At baseline, the mice had increased body weight, larger adipocytes, fatty liver, intestinal atrophy, and impaired intestinal barrier function. After 12 weeks of Gel-B 2 or 4% treatment, body weight and adipocyte size were significantly reduced compared to mice continuously fed HFD. Gel-B treatment also prevented intestinal atrophy induced by HFD. Intestinal permeability, as measured by the amount of serum FITC-dextran (4 kDa) 4 hours after oral administration, was reduced in both Gel-B groups compared to HFD control. These data support the hypothesis that Gel-B may protect against and reverse the harmful effects of HFD and future research could explore its therapeutic benefit in the presence of hepatic steatosis and aggressive forms of fatty liver disease.
Alessandra Silvestri, PhD, of the Laboratory of Mucosal Immunology and Microbiota at Humanitas Research Hospital will provide a recorded overview of these results and will be available for virtual questions by meeting participants.
“In multiple different mice models, we consistently see the same intestinal tissue repair in response to the mechanical forces applied by the Gelesis hydrogels,” said Elaine Chiquette, PharmD, Gelesis’ Chief Scientific Officer. “We are excited to translate these mechanobiological therapeutic effects into upcoming clinical trials.”
Gelesis is developing a novel hydrogel platform technology to treat overweight and obesity and chronic diseases related to the GI pathway. Gelesis’ proprietary approach is designed to act mechanically in the GI pathway to potentially alter the course of certain chronic diseases. In April 2019, Gelesis received FDA clearance for its lead product candidate, Plenity®, as an aid for weight management in overweight and obese adults with a Body Mass Index (BMI) of 25-40 kg/m2, when used in conjunction with diet and exercise. It was also granted a CE Mark, which allows Gelesis to market Plenity in the European Economic Area. Plenity is currently available in limited release in the U.S. Additionally, Gelesis is developing additional investigational candidates such as Gelesis200, a hydrogel optimized for weight loss and glycemic control in patients with type 2 diabetes and prediabetes. Novel hydrogel mechanotherapeutics based on the Gelesis platform technology are also being advanced in other GI inflammatory conditions, such as non-alcoholic steatohepatitis (NASH) and functional constipation. For more information, visit gelesis.com or connect with us on Twitter @GelesisInc.
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