BioMarin and the n-Lorem Foundation will develop the first investigational antisense oligonucleotide therapy for ReNU syndrome, a rare RNU4-2 genetic disorder with no approved treatments.
Written By: Umesh Hanumante,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
BioMarin Pharmaceutical and the n-Lorem Foundation have formed a strategic collaboration and global exclusive license agreement to develop what could become the first disease-targeted therapy for ReNU syndrome. The investigational antisense oligonucleotide (ASO) program focuses on the RNU4-2 (n.64_65insT) genetic variant, the most commonly known disease-causing mutation associated with the condition.
The agreement combines BioMarin’s expertise in genetic medicine development with n-Lorem’s experience in personalized antisense therapies for ultra-rare diseases. The companies will jointly conduct preclinical studies before selecting a lead ASO candidate for clinical development. BioMarin will lead global clinical development and commercialization if the program advances successfully.
Antisense Technology Targets the Genetic Cause of ReNU Syndrome
ReNU syndrome is a rare neurodevelopmental disorder caused by pathogenic variants in the RNU4-2 gene. The condition is associated with cognitive impairment, language deficits, and adaptive behavioral challenges. It was first identified as a distinct genetic syndrome in 2024 through research led by Dr. Nicola Whiffin at the University of Oxford’s Big Data Institute and Dr. Ernest Turro at the Icahn School of Medicine at Mount Sinai.
Unlike treatments that address symptoms, antisense oligonucleotides work by binding to specific RNA sequences to modify gene expression or RNA processing. The investigational therapy is intended to correct the underlying molecular defect caused by the RNU4-2 (n.64_65insT) variant, offering a precision medicine approach for affected individuals.
There are currently no approved therapies that target the genetic cause of ReNU syndrome.
Development Program Focuses on the Most Common Disease Variant
The collaboration will initially evaluate multiple preclinical ASO candidates before selecting the most promising molecule for clinical testing. The target mutation is estimated to account for approximately 75% of all diagnosed ReNU syndrome cases, potentially allowing the therapy to benefit a substantial proportion of affected patients.
The companies have not disclosed a timeline for initiating clinical trials. No efficacy or safety data are currently available because the program remains in the preclinical stage.
The n-Lorem Foundation had already begun developing individualized ASO therapies for several patients with RNU4-2 variants and plans to initiate individualized clinical studies in the coming months. Through the new agreement, BioMarin will expand development beyond individualized treatment toward a commercially available therapy for the broader ReNU syndrome population.
Leadership Highlights Scientific and Development Strategy
Kevin Eggan, Ph.D., Chief Scientific Officer at BioMarin, said the discovery of ReNU syndrome in 2024 provided long-awaited diagnostic answers for many families but emphasized that no therapies currently address the disease’s underlying genetic cause. He noted that combining BioMarin’s genetic medicine capabilities with n-Lorem’s antisense expertise could accelerate development of the first targeted treatment for the disorder.
Stanley T. Crooke, M.D., Ph.D., Founder, Chairman and Chief Executive Officer of the n-Lorem Foundation, said the partnership reflects the foundation’s model of collaborating with experienced biotechnology companies when promising ASO programs have the potential to benefit larger patient populations. He added that BioMarin’s clinical development and commercialization capabilities make it well positioned to advance the therapy globally.
Path Forward
ReNU syndrome is projected to become one of the leading monogenic causes of developmental delay, with an estimated global patient population of approximately 100,000. If successful, the BioMarin-n-Lorem collaboration could establish the first targeted therapy for this newly recognized disorder while expanding the application of antisense technology beyond individualized treatment into broader rare disease development.
The partners will now complete preclinical evaluation, nominate a lead ASO candidate, and prepare the program for future clinical studies and regulatory advancement.
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About the Writer
Umesh Hanumante (M.Pharm) (LinkedIn) is a pharmacy professional and healthcare writer with a background in Regulatory Affairs, pharmaceutical innovation, and clinical research. He has around two years of industry experience as an Executive PMT at Troikaa Pharmaceuticals Ltd and qualified GPAT 2024. His areas of interest include regulatory compliance, dossier preparation, clinical trials, emerging therapies, and advancements in the global pharmaceutical and healthcare sector.