RNA specialist ProQR Therapeutics NV bags US$8.1m funding

RNA editing specialist ProQR Therapeutics NV has extended its collaboration with the Rett Syndrome Research Trust (RSRT). Building on an initial $1m research grant announced in January 2024, theRSRT has now greenlighted an additional US$8.1m in funding to advance AX-2402 into clinical trials.

AX-2402 is being developed for individuals with Rett syndrome who have the R270X mutation in the disease-causing MECP2 gene. It is based on ProQR’s proprietary Axiomer RNA editing platform. Axiomer can target many mutations beyond R270X that collectively impact a large segment of the Rett population. Success with AX-2402 sets the foundation for developing RNA editing therapeutics to target the remaining mutations.

In RNA editing, researchers harness the naturally-occurring Adenosine Deaminases Acting on RNA (ADAR) proteins to make specific changes to mRNA. This allows editing to occur at the mRNA level rather than at the DNA level. Since ADAR editing of MECP2 mRNA targets the underlying genetic mutation causing Rett syndrome, it offers a path toward restoring normal cell function without changing DNA.

The additional $8.1 million in funding will enable ProQR to accelerate work on RNA editing approaches tailored to the genetic mutations that cause Rett Syndrome. This next phase of the collaboration will focus on optimising therapeutic candidates targeting the transcription factor Methyl CpG binding protein 2 (MECP2) and advancing them toward clinical development. “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,” ecxplains ProQR Therapeutics CSO and co-founder Gerard Platenburg.

ProQR next-generation RNA base editing technology Axiomer^™ has shown potential to yield a new class of medicines for diverse types of diseases. Axiomer^™ “Editing Oligonucleotides”, or EONs, mediate single nucleotide changes to RNA in a highly specific and targeted way using molecular machinery that is present in human cells called ADAR (Adenosine Deaminase Acting on RNA). Axiomer^™ EONs are designed to recruit and direct endogenously expressed ADARs to change an Adenosine (A) to an Inosine (I) in the RNA – an Inosine is translated as a Guanosine (G) – correcting an RNA with a disease-causing mutation back to a normal (wild type) RNA, modulating protein expression, or altering a protein so that it will have a new function that helps prevent or treat disease.

Rett syndrome is a progressive neurodevelopmental disorder caused by genetic mutations in the Methyl CpG binding protein 2 (MECP2) and diagnosed primarily in females. It is characterized by apparently normal psychomotor development during the first six to 18 months after birth, followed by a period of developmental stagnation, then a regression in language and motor skills, followed by long-term relative stability. During the phase of regression, affected patients develop repetitive, stereotypic hand movements that replace purposeful hand use. Additional symptoms include gait ataxia and apraxia, seizures, tremors, episodic apnea and/or hyperpnea, gastrointestinal issues, scoliosis and musculoskeletal problems, anxiety and sleep issues and bruxism.

ProQR Therapeutics has patent protection for Axiomer platform in China, Canada, Israel, New Zealand, Japan, Russia, South Africa, the US and Europe