Tudca for vision and obesity
TUDCA is an important molecule to highlight on your website about Bardet-Biedl Syndrome (BBS) because it offers a unique and promising approach to slowing retinal degeneration, which is one of the most debilitating features of BBS. It works by reducing cellular stress in photoreceptors, specifically targeting the endoplasmic reticulum and mitochondrial stress pathways that lead to cell death. This is especially relevant in BBS1, where mistrafficking of proteins and lipids in the retina creates chronic stress within the photoreceptor cells. TUDCA helps stabilize these cells and prevent them from undergoing apoptosis, which is the final step in their degeneration.
While NAC (N-acetylcysteine) is already being used or considered for its antioxidant properties, TUDCA is not redundant. NAC helps by reducing oxidative stress and scavenging reactive oxygen species, which are harmful byproducts that accumulate in diseased retinal cells. TUDCA, on the other hand, acts further downstream in the stress pathway, helping the cells survive once stress has already taken hold. It prevents the activation of apoptosis triggered by ER stress and mitochondrial dysfunction, which are especially relevant in BBS. Using both NAC and TUDCA may provide a broader protective effect by targeting multiple parts of the degenerative cascade that affects vision in BBS.
The study by Drack et al. (2012) demonstrated that TUDCA preserved visual function and retinal structure in a mouse model of BBS1. It also had the added benefit of reducing obesity in these mice, another common symptom in BBS. These findings make TUDCA a strong candidate for inclusion in future treatment strategies for BBS-related retinal degeneration.
The reference to the paper is below.
Dosage and safety profile
The study administered 500 mg/kg TUDCA subcutaneously to mice, twice a week. To scale this to a human child, we use allometric scaling based on body surface area (BSA). The standard formula for dose translation between species (as per FDA guidelines) is Human equivalent dose (HED) in mg/kg = Animal dose in mg/kg × (Animal Km / Human Km). This leads to a conversion of ~430 mg/day for a 25kg and ~810 mg/day for a 70kg human.
TUDCA is generally safe and well-tolerated in humans—even in infants and in adult trials at doses ~1,750 mg/day. But at high doses, bile acids can cause liver toxicity (hepatotoxicity), especially with long-term use. TUDCA is less hepatotoxic than other bile acids like CDCA or DCA, but liver enzymes should be monitored regularly during treatment.
The mouse study only went daily in the fastest-degenerating models, which also didn’t tolerate it well (weight loss, dropouts). We don’t have clear long-term safety data in kids at high daily doses. High bile acid loads over time can be hepatotoxic — even if TUDCA is one of the least toxic ones.
Key papers:
Drack, A. V., Dumitrescu, A. V., Bhattarai, S., Gratie, D., Stone, E. M., Mullins, R., & Sheffield, V. C. (2012). TUDCA slows retinal degeneration in two different mouse models of retinitis pigmentosa and prevents obesity in Bardet-Biedl Syndrome type 1 mice. Investigative Ophthalmology & Visual Science, 53(1), 100–106. https://doi.org/10.1167/iovs.11-8544
[From: https://www.bardetbiedl.org/news/from-the-bbs-center-of-excellence]
“A letter to BBS families from Dr. Bob Haws, director of the BBS Center of Excellence at the Marshfield Clinic.
Dear BBS family members,
As a physician caring for children with BBS I am impressed that a leading priority for you and others is preserving vision for your loved one or yourself. As a father of a wonderful daughter affected by blindness I understand your passion. A second priority for individuals with BBS is prevention of obesity by appetite control. The two issues of loss of vision and appetite control are critical to almost every child with BBS. The University of Iowa has published encouraging research reporting that tauroursodeoxycholic acid (TUDCA) slowed retinal degeneration in an animal model of BBS. Furthermore TUDCA resulted in decreased food consumption and weight loss in the animals.
A clinical trial of TUDCA in individuals with BBS has been proposed but not yet initiated. Such clinical trials are very expensive. Dr. Arlene Drack at the University of Iowa is pursuing funding. The Foundation Fighting Blindness has expressed interest in considering TUDCA research. I strongly encourage you to write Dr. Steve Rose, Chief Science Officer at the Foundation Fighting Blindness expressing support, and your family’s interest in participating in a clinical trial of TUDCA in individuals with BBS. Contact information for the Foundation Fighting Blindness is provided below:
Foundation Fighting Blindness
7168 Columbia Gateway Drive, Suite 100
Columbia, MD 21046
E-mail: info@FightBlindness.org
Toll Free: (800) 683-5555
Important points to consider in your communication may include the following:
1) The treatment results with TUDCA in an appropriate animal model of BBS are extremely encouraging. Translational research, taking research from laboratory animals to humans, is critical. This research is integral to the objective of the FFB.
2) Bardet-Biedl syndrome provides an important disease model for other degenerative retinal diseases. Successful identification of effective therapy in BBS may be applicable to other diseases causing blindness.
3) The Bardet-Biedl Syndrome community is a growing community with a commitment to research. You may consider stating that you represent one individual anxious to support and participate in this research.
4) TUDCA provides hope to the BBS community not only for the potential benefit on vision but also for the appetite suppressing effect that will improve the quality of life for individuals with BBS.
Please take time to send your support for this research. Your voices are extremely powerful and need to be heard.
While we are hopeful for a TUDCA clinical trial, remember that there are no reliable and safe sources of TUDCA available for individuals today. Attempting to self-medicate with TUDCA is dangerous.
Bob Haws, M.D.
Pediatric Nephrology
Medical Director
Treatment Center for Bardet-BIedl Syndrome and Related Ciliopathies
haws.robert@marshfieldclinic.org
2014