- In January 2025, Ionis Pharmaceuticals announced preclinical results for ION-CEP290-2.5Rx, an antisense oligonucleotide (ASO) therapy targeting CEP290 mutations associated with Joubert Syndrome.Ionis reported promising in vivo data demonstrating that ION-CEP290-2.5Rx significantly restored CEP290 protein expression and improved ciliary function in animal models. The therapy specifically targets the aberrant splicing caused by CEP290 mutations—a major contributor to Joubert pathology—offering a mutation-specific intervention. These findings support the potential of ASO platforms in treating ciliopathies like Joubert Syndrome and position Ionis to enter IND-stage development by late 2025, pending toxicology validation
- In October 2024, Regenxbio initiated IND-enabling studies for a gene therapy candidate aimed at TMEM67 mutations in Joubert patients, with Phase I trials expected to begin in early 2026.The candidate therapy leverages Regenxbio’s NAV® AAV9 vector platform, designed to deliver a functional copy of the TMEM67 gene directly to cerebellar and renal tissues affected in Joubert Syndrome. Preclinical data from animal models have shown successful CNS transduction and gene expression. This program marks one of the first gene therapies specifically addressing TMEM67-associated Joubert subtypes, which are linked to both neurological and renal involvement
- In August 2024, Roche began a collaborative pediatric neurological research program with U.S. universities to investigate molecular pathways underlying Joubert-related cerebellar hypoplasia.This multi-institutional initiative focuses on dissecting the signaling mechanisms disrupted in cerebellar development, particularly those regulated by ciliopathy-associated genes such as AHI1, CC2D2A, and TMEM67. The partnership includes advanced imaging, transcriptomic profiling, and iPSC-derived neuronal models to map disease pathways and identify viable molecular targets. Findings from this effort are expected to inform novel therapeutic approaches and neuroprotective strategies for early-onset Joubert Syndrome
- In March 2024, Amicus Therapeutics received Orphan Drug Designation (ODD) from the U.S. FDA for a novel substrate reduction therapy (SRT) targeting renal dysfunction in Joubert Syndrome.The investigational therapy aims to mitigate nephronophthisis—a common and progressive renal manifestation in Joubert patients—by reducing the accumulation of toxic metabolites that impair kidney function. Amicus’s candidate works through a small-molecule mechanism designed for chronic administration and has shown early promise in preclinical nephron models. The ODD status provides regulatory incentives such as tax credits, user fee waivers, and potential market exclusivity, accelerating the development pathway
