Non-Alcoholic Fatty Liver Disease (NAFLD)
Clinical development plans are in place for the registration of a short-term, double-blind, randomized controlled, cross-over clinical study in Obese subjects with NAFLD as to obtain specific health claims recognized by national and international regulatory authorities for our unique nutraceutical approach.
Non-Alcoholic Fatty Liver Disease (NAFLD) is defined by the presence of a determined hepatic steatosis, which corresponds to an accumulation of triglycerides in hepatocytes representing more than 5% of the total weight of the liver, in the absence of significant alcohol consumption, of the use of steatogenic drugs (tamoxifen or amiodarone) and of another liver pathology (viral or autoimmune hepatitis, hemochromatosis, Wilson's disease, …) (Chalasani et al. 2012; Neuschwander-Tetri 2003). NAFLD distinguishes liver steatosis (non-alcoholic fatty liver, NAFL) from non-alcoholic steatohepatitis (NASH) (Chalasani et al. 2012). NAFL, which corresponds to the first stage of NAFLD and is considered to be a benign, asymptomatic and reversible condition, is defined by the presence of hepatic steatosis (≥ 5%) without evidence of hepatocytes ballooning (Chalasani et al. 2012; Neuschwander-Tetri 2003; Spengler and Loomba 2015). In some patients, NAFL may progress to a serious and irreversible pathological condition, non-alcoholic steatohepatitis (NASH), which is characterized by the presence of hepatic steatosis associated with inflammation and hepatocytes ballooning that causes their dysfunction and death. This condition, which may or may not be accompanied by the presence of fibrosis, may progress to cirrhosis, liver failure and, in rare cases, to liver cancer (Chalasani et al. 2012; Spengler and Loomba 2015).
Based on an epidemiological study that identified NAFLD cases in published scientific studies, the overall prevalence of NAFLD is 25% (Younossi et al. 2016). In a worrying way, this prevalence increased sharply, from 15 to 25% between 2005 and 2010 (Younossi et al. 2016). While NAFL remains considered as a benign and poorly symptomatic condition, its progression to NASH and the onset of co-morbidities, such as atherosclerosis or type 2 diabetes mellitus (T2DM), are major health problems. Among the leading causes of death in NAFLD patients, cardiometabolic complications are extremely common, including coronary heart disease and T2DM (Rafiq et al. 2009).
The ever-increasing pandemic of Obesity fuels NAFLD prevalence and, as such, NASH has become one of the most common liver disorders. NASH is a critical public health concern with high unmet medical needs and remains widely untreated. Despite major efforts by the industry, no approved therapies are marketed.
Treatment of NAFL-NASH
To date, no pharmacological treatment can cure NAFL, which clearly promotes the further development of NASH and related comorbidities (El-Agroudy et al. 2019). According to the European Association for the Study of the Liver (EASL), the European Association for the Study of Diabetes (EASD), and the European Association for the Study of Obesity (EASO), the current guidelines for the management of NAFL recommend lifestyle modification as the strategy of choice for preventing and improving NAFL, including caloric restriction and physical activity (Anon 2016). If lifestyle modifications are effective to improve the outcome of NAFL, or at least to limit its progression to NASH and other comorbidities, the evidence from both dietary and exercise interventions is limited regarding the effectiveness in more advanced stages, such as NASH (El-Agroudy et al. 2019). In addition, patients' compliance with these types of intervention remains relatively low. Indeed, caloric restriction is difficult to practice in the long term and increases the risk of malnutrition, which explains, in particular, the low compliance of patients (Golbidi et al. 2017; Madeo et al. 2019).
- Therefore, there is a real need to treat NAFL-NASH patients early and at a stage when the disease is potentially still reversible.
- A therapeutic solution that has the ability to address multiple factors that initiate the progression of NASH will provide clinical benefit
- The co-development along with the CLM-BM-001 biomarker signature allows for functional endpoints enabling to obtain specific health claims recognized by national and international regulatory authorities for our unique nutraceutical approach.
CellMade’s approach towards early and preventive nutraceutical treatment of NAFL-NASH
As part of our innovation road map to address the unmet needs in NAFLD, we are rapidly advancing an early, preventive nutraceutical therapy program based on the modulation of key factors responsible for the onset of noxious pathways leading to the further progression of NASH (Program: CM-101). The CLM-101 mechanism of action is thereby well-positioned as an early and preventive nutraceutical treatment, complementary to existing recommendations for lifestyle modifications and potentially within combination regimens.
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