Emerging Therapeutic Targets and Experimental Drugs for the Treatment of NAFLD.
Pratima DibbaAndrew A LiBrandon J PerumpailNimy JohnSandy SallamNeha D ShahWaiyee KwongGeorge CholankerilDonghee KimAndrew A LiPublished in: Diseases (Basel, Switzerland) (2018)
The two main subsets of nonalcoholic fatty liver disease (NAFLD) include: (1) nonalcoholic fatty liver (NAFL), the more common and non-progressive subtype; and (2) nonalcoholic steatohepatitis (NASH), the less common subtype, which has the potential to progress to advanced liver damage. Current treatment strategies have focused on lifestyle management of modifiable risk factors, namely weight, and on the optimization of the management of individual components of metabolic syndrome. Various hypothetical pathogenic mechanisms have been proposed, leading to the development of novel drugs with the potential to effectively treat patients with NASH. Numerous clinical trials are ongoing, utilizing these experimental drugs and molecules targeting specific mechanistic pathway(s) to effectively treat NASH. Some of these mechanistic pathways targeted by experimental pharmacologic agents include chemokine receptor 2 and 5 antagonism, inhibition of galectin-3 protein, antagonism of toll-like receptor 4, variation of fibroblast growth factor 19, agonism of selective thyroid hormone receptor-beta, inhibition of apoptosis signal-regulating kinase 1, inhibition of acetyl-coenzyme A carboxylase, agonism of farnesoid X receptor, antibodies against lysl oxidase-like-2, and inhibition of inflammasomes. Emerging data are promising and further updates from ongoing clinical trials are eagerly awaited.
Keyphrases
- toll like receptor
- clinical trial
- metabolic syndrome
- risk factors
- oxidative stress
- weight loss
- physical activity
- nuclear factor
- cancer therapy
- multiple sclerosis
- immune response
- body mass index
- binding protein
- cell death
- adipose tissue
- type diabetes
- big data
- drug delivery
- human health
- randomized controlled trial
- risk assessment
- small molecule
- tyrosine kinase
- climate change
- uric acid
- skeletal muscle
- artificial intelligence
- body weight
- deep learning
- fatty acid
- liver fibrosis
- phase iii