While the preclinical evidence is promising, it is not currently possible to conclude whether TUDCA is of therapeutic benefit to people with neurodegenerative diseases because of the lack of clinical trials. A detailed explanation is provided below.
As described elsewhere in this FAQ, the endoplasmic reticulum (ER) is an organelle inside cells that folds proteins so they can function properly.[1][2][3] Certain physiological conditions can cause ER stress, which results in an unfolded protein response and causes inflammation, fibrosis, or apoptosis (cell death).[1][2][3] ER stress and the unfolded protein response can be detected in neuronal cells from animal models of neurodegenerative diseases, including Parkinson's disease, Huntington's disease, and Alzheimer's disease.[4][5] Because in vitro and animal studies have shown that TUDCA can prevent ER stress and the consequences of the unfolded protein response, it has become a metabolite of interest in the search for therapies for neurodegenerative diseases.[4][5]
There is a promising body of evidence derived from preclinical experiments demonstrating the therapeutic properties of TUDCA in in vitro and animal models of Parkinson's, Huntington's, and Alzheimer's.[5][6] However, there are no published randomized controlled trials that examine TUDCA’s clinical efficacy on Parkinson's disease or Huntington's disease, and the only published trial on Alzheimer’s disease — the PEGASUS trial, which tested the effect of sodium phenylbutyrate combined with TUDCA — found no benefit on the primary clinical efficacy outcomes when using an intention-to-treat analysis.[7] That said, the PEGASUS trial did reveal beneficial effects on some but not all of the neurogenerative biomarkers measured in the cerebrospinal fluid (CSF), with no benefit to biomarkers of inflammation or metabolic health.[7]