nL-TUBB4-001

nL-TUBB4-001 is a personalized, experimental antisense oligonucleotide (ASO) therapy developed by the n-Lorem Foundation for the treatment of TUBB4A-related leukodystrophy, specifically Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-ABC). The drug is designed as a 20-mer Gapmer consisting of a 10-base DNA core flanked by five 2′-O-methoxyethyl (2′-MOE) modified ribose wings with a full phosphorothioate (PS) backbone. Its mechanism of action involves non-allele-selective binding to the *TUBB4A* mRNA, which recruits RNase H to induce degradation of the transcript. H-ABC is typically caused by gain-of-function mutations in the *TUBB4A* gene, leading to the production of toxic tubulin beta-4A proteins that disrupt oligodendrocyte maturation and myelin stability. By reducing the overall levels of TUBB4A expression, nL-TUBB4-001 aims to mitigate the neurodegenerative effects of the mutant protein. The therapy is administered via intrathecal injection and is currently being evaluated in individual-patient (n-of-1) clinical protocols.

Other names

nL-TUBB4-001nL-TUBB-4-001nL-TUBB 4-001