Joubert Syndrome
Joubert syndrome stems from mutations in genes related to cilia and is characterized as a rare neurodevelopmental disorder. Protheragen has allocated Joubert syndrome's multifaceted issues to advanced technologies, specialized professionals, and therapeutic innovation construction. With us, the comprehensive support services provided will aid you in seamlessly navigating the entire process from drug candidate development to market entry.
Introduction to Joubert Syndrome
Joubert syndrome is a rare autosomal recessive neurodevelopmental disorder characterized by congenital malformations of the cerebellum and brainstem, resulting in the hallmark "molar tooth sign" (MTS) on axial brain MRI. First described in 1969, JS has an estimated prevalence of 1 in 80,000–100,000 live births, placing it among the most well-defined ciliopathies—a class of disorders caused by dysfunctional primary cilia.
Fig.1 Range of organ involvement in Joubert syndrome and classification in clinical subgroups (in bold). (Romani M, et al., 2013)
Pathogenesis of Joubert Syndrome
Joubert syndrome mostly occurs due to alterations in more than 40 cilia-associated genes (reflectively, CEP290, TMEM67, and AHI1) which impair the structure and function of primary cilia, especially at the transition zone. These genetic abnormalities disrupt both intraflagellar transport and hedgehog signaling pathways, resulting in characteristic cerebellar vermis hypoplasia and malformations of the brainstem. This form of ciliopathy disrupts the normal neuronal migration processes during brain development, leading to the key neurological features of the syndrome such as hypotonia, ataxia, and breathing irregularities.
Fig.2 IFT74 is identified as a Joubert syndrome-associated gene in the Chinese population. The variants interfere with intra-flagellar transport and ciliary signaling. (Luo M, et al., 2021)
| Drug Names | Mechanism of Action | Targets | Research Phase |
| EDIT-101 | EDIT-101 is a gene therapy that uses gene editing-mediated exon skipping to restore normal CEP290 gene expression in retinal cells. | CEP290 gene | Phase I/II |
| Levetiracetam | Modulates neurotransmitter release through binding to the synaptic vesicle protein 2A (SV2A), helping to control seizures associated with the syndrome. | Synaptic vesicle protein 2A (SV2A) | Approved |
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
Recognizing the complexity of diagnosing and treating Joubert syndrome, Protheragen is committed to building a team of experts to provide cutting-edge diagnostic and therapeutic development solutions. Our commitment lies in providing a variety of customized therapy development services to meet the diverse research needs of our customers. We also excel in generating precise disease models that are carefully engineered to replicate the unique features of Joubert syndrome.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- JBTS17 Mutant Model
- Ahi1 Mutant Model
- Cep290 Mutant Model
- Talpid3 Conditional Knockout Model
- Pibf1 Knockdown Model
- Other Model
At Protheragen, we are committed to supporting the development of innovative therapeutics through comprehensive preclinical research services, including pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies. Our customized approach addresses the unique challenges of your studies and helps you optimize your drug candidates for commercial success. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Romani M, Micalizzi A, Valente E M. Joubert syndrome: congenital cerebellar ataxia with the molar tooth[J]. The Lancet Neurology, 2013, 12(9): 894-905.
- Luo M,Lin Z, Zhu T, et al. Disrupted intraflagellar transport due to IFT74 variants causes Joubert syndrome[J]. Genetics in Medicine, 2021, 23(6): 1041-1049.