Obesity in Bardet-Biedl Syndrome (BBS)
Obesity is a cardinal feature of Bardet-Biedl Syndrome (BBS), often emerging early in life and contributing significantly to the overall disease burden. However, the severity and characteristics of obesity can vary depending on the specific genetic subtype of BBS.
For instance, individuals with BBS1 mutations tend to exhibit a milder obesity phenotype, both in terms of body mass index (BMI) trajectory and associated metabolic complications. This contrasts with subtypes such as BBS10 or BBS12, where obesity is typically more severe and often co-occurs with insulin resistance, hyperphagia, and early-onset type 2 diabetes.
The obesity observed in BBS may not be solely due to increased caloric intake; rather, it reflects complex dysfunctions in hypothalamic signaling and energy homeostasis.
Therapeutic avenues
There are presently no clinical trials for BBS-related obesity or hyperphagia beyond setmelanotide, an MC4R agonist, which is the first FDA-approved therapy specifically targeting obesity in BBS. It addresses the hypothalamic melanocortin pathway dysfunction and has shown significant and sustained weight loss in clinical trials.
Tauroursodeoxycholic acid (TUDCA) has been investigated in preclinical studies involving BBS1 mouse models, demonstrating potential benefits in preserving retinal function and mitigating obesity.
There is some evidence that Caffeine may support mitochondrial function in BBS by enhancing DRP1 activity, potentially improving energy metabolism and reducing obesity-related symptoms.
Obesity – simple summary
- Obesity and hungriness are widespread symptoms in BBS.
- It is not exactly clear why, but likely involves disruptions in the body’s hungriness signaling as well as its energy metabolism.
- Setmelanotide (branded Imcivree by Rhythm Pharmaceuticals) is the only medicine that has been approved specifically for BBS, and has shown to be significantly beneficial in combating obesity and hyperphagia for BBS patients.
- However, this setmelanotide medicine needs to be used continuously and is very expensive – therefore insurance coverage is important. (Many major US insurers cover it with prior authorization for patients with a confirmed diagnosis of BBS and obesity, but this varies by situation and geography. We understand that the medication has received coverage designation under public insurance plans by certain regulatory authorities in some European countries.)
- There is some evidence on BBS mouse models that TUDCA and caffeine may have a positive effect on obesity. There is good evidence that certain doses of these compounds are safe, even for long-term use.
🔷 If you have experience with any of these compounds and their effects in BBS, we would love to hear from you on: info [ @ ] bbs-hub.org