Bardet-Biedl syndrome (BBS) is a rare condition with multi-systemic features, classified as a ciliopathy due to its multi-organ system ailments. Its renal manifestation is especially severe. Protheragen utilizes specialized preclinical research services to take on the genetic intricacies of kidney disorders to address the challenges posed by the pathogenesis of this disease.
Introduction to Bardet-Biedl Syndrome
Bardet-Biedl syndrome was first noted in the early 1900s and is considered a rare, extensively diverse genetic disease. It follows an autosomal recessive inheritance pattern, although other, more convoluted modes of inheritance have also been documented. This syndrome stems from mutations in one of several known BBS genes. These mutations are responsible for the BBS phenotype due to dysfunction of primary cilia, cellular organelles that are important for signaling during the developmental phase of the organism.
Pathogenesis of Bardet-Biedl Syndrome
Bardet-Biedl Syndrome (BBS) exists as a unique heritable syndrome with the characteristic features of retinal dystrophy and polydactyly along with morbid obesity. It results from mutations in the genes responsible for the amplification of a primary cilium in the cell and its exacerbating cellular signaling and sensory pathways. Defective cilia phenomena disrupt processes as elemental as Shh signal transduction, which results in propensity for multisystemic Shh pathway perturbation as evident from the list of growing comorbidities.
Fig.1 Heterogeneity in Bardet Biedl Syndrome-determinants and clinical effects. (Florea, Caba and Gorduza, 2024)
Therapeutic Development for Bardet-Biedl Syndrome
| Therapeutic Strategy |
Therapeutic Target |
Key Findings/Mechanism |
Key Challenges/Limitations |
Development Stage |
| Gene Therapy |
|
|
|
|
| AAV-Mediated Gene Replacement |
BBS1/BBS10 cDNA delivery |
Subretinal injection preserves photoreceptors (mouse models) |
Immune response, tissue-specific delivery |
Preclinical / Phase I planned |
| CRISPR-Cas9 Editing |
Corrects BBS nonsense mutations |
High correction efficiency in iPSC-derived renal cells |
Off-target effects, ethical concerns |
Preclinical optimization |
| Exon Skipping (ASOs) |
Skips pathogenic exons (e.g., BBS5) |
Restores BBSome assembly in vitro |
Limited to splice-site mutations |
Preclinical |
| Pharmacological Interventions |
|
|
|
|
| Small Molecule Chaperones |
Stabilizes BBS protein folding |
Rescues ciliary trafficking defects in BBS2/9 models |
Limited to specific mutations |
Preclinical |
| Ciliary Signaling Modulators |
Targets cAMP/PKA pathways |
Improves cilia function in BBS renal models |
Lack of tissue specificity |
Early discovery |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen has developed sophisticated disease models for Bardet-Biedl syndrome (BBS) and provides preclinical therapeutic development services. Our research seeks to explain the complex genetic and molecular pathways of ciliary dysfunction resulting from BBS gene mutations with renal features.
Therapeutic Development Platform for Bardet-Biedl Syndrome
Protheragen combines deep expertise in kidney developmental biology and advanced molecu
lar and cellular technologies to deliver tailored solutions for BBS research.
Disease Models Development for Bardet-Biedl Syndrome
Protheragen offers innovative and comprehensive disease models to advance preclinical research of BBS. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the genetic and functional disruptions caused by BBS gene variants, supporting extensive drug discovery and mechanism-based investigations.
- BBS patient-derived renal epithelial cell lines
- Retinal pigment epithelial (RPE) cells
- Human mesenchymal stem cells (hMSCs)
- BBS patient-derived kidney organoid
- Brain organoids with BBS gene mutations
- Bbs gene mutant mouse models
- Bbs conditional knockout mouse models
- Bbs mutant rat models
- Zebrafish bbs mutant lines
- Xenopus bbs gene knockdown models
Protheragen offers integrated preclinical therapeutics and drug development solutions specifically designed for research in rare genetic kidney diseases like Bardet-Biedl syndrome. We specialize in custom disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your investigation from initial discovery through to preclinical validation, offering a full-range, one-stop service for renal-related therapy development.
If you are interested in our services and advancing research for Bardet-Biedl syndrome, please don't hesitate to contact us.
References
- Florea, L., L. Caba, and E. V. Gorduza. "Bardet-Biedl Syndrome-Multiple Kaleidoscope Images: Insight into Mechanisms of Genotype-Phenotype Correlations." Genes (Basel) 12.9 (2021).
- Shoemaker, A. "Bardet-Biedl Syndrome: A Clinical Overview Focusing on Diagnosis, Outcomes and Best-Practice Management." Diabetes Obes Metab 26 Suppl 2 (2024): 25-33.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
