ProQR Therapeutics has received an additional $8.1 million in funding from the Rett Syndrome Research Trust (RSRT) to accelerate the development of AX-2402, an RNA editing therapy for Rett syndrome. This funding builds upon an initial $1 million research grant awarded in January 2024 and aims to advance AX-2402 into clinical trials, offering hope for individuals with this challenging neurodevelopmental disorder.
AX-2402: Targeting the R270X Mutation
AX-2402 is specifically designed for individuals with Rett syndrome who carry the R270X mutation in the MECP2 gene. This therapy leverages ProQR’s proprietary Axiomer RNA editing platform, which has the potential to address various mutations beyond R270X that collectively impact a significant portion of the Rett syndrome population. The success of AX-2402 could pave the way for developing RNA editing therapeutics targeting other mutations associated with the disease.
How Axiomer Works: RNA Editing for Precision
RNA editing involves harnessing naturally occurring Adenosine Deaminases Acting on RNA (ADAR) proteins to make precise modifications to mRNA. This approach allows for editing at the mRNA level rather than at the DNA level. By targeting the underlying genetic mutation in the MECP2 mRNA, Axiomer aims to restore normal cell function without altering the DNA itself. According to ProQR Therapeutics CSO and co-founder Gerard Platenburg, "In Rett syndrome, the dosage of MECP2 is crucial. With RNA editing, you are using the cell’s natural regulation system to get the precise expression level."
Advancing Towards Clinical Development
The additional funding will enable ProQR to optimize therapeutic candidates that target the Methyl CpG binding protein 2 (MECP2) transcription factor and advance them towards clinical development. ProQR's next-generation RNA base editing technology, Axiomer, has demonstrated the potential to create a new class of medicines for diverse diseases. Axiomer “Editing Oligonucleotides,” or EONs, facilitate single nucleotide changes to RNA in a highly specific and targeted manner, utilizing molecular machinery present in human cells called ADAR (Adenosine Deaminase Acting on RNA).
Rett Syndrome: A Complex Neurodevelopmental Disorder
Rett syndrome is a progressive neurodevelopmental disorder primarily diagnosed in females, caused by genetic mutations in the MECP2 gene. It is characterized by a period of normal psychomotor development during the first 6 to 18 months, followed by developmental stagnation and regression in language and motor skills. Patients often develop repetitive hand movements, gait ataxia, seizures, and other neurological and gastrointestinal issues. Rett syndrome affects approximately 1 in 10,000 to 15,000 female births worldwide.
ProQR Therapeutics holds patent protection for the Axiomer platform in several key markets, including China, Canada, Israel, Japan, Russia, South Africa, the US, and Europe, underscoring the global potential of this innovative RNA editing technology.
