Arthex Biotech has published new preclinical data demonstrating central nervous system (CNS) activity of its investigational antimiR-23b therapy, ATX-01, in myotonic dystrophy type 1 (DM1). ATX-01 is ARTHEx’s investigational RNA therapeutic designed to address the underlying genetic cause of DM1, a highly disabling neuromuscular disorder with no known cure or approved treatment.
The study, titled “Fatty-acid–based antimiR-23b delivery in the DMSXL model: a potential therapeutic strategy for brain dysfunction in Myotonic Dystrophy Type 1,” provides the first known scientific evidence linking molecular correction in the brain with functional behavioural improvements in a DM1 animal model, representing a significant advancement for the field. The study was published in Cell Reports Medicine.
DM1 is a multisystemic neurological disorder affecting not only muscle but also the brain, where patients experience cognitive impairment, behavioral changes, and reduced quality of life. Despite this, most therapeutic approaches have historically been unable to effectively reach the central nervous system (CNS).
“This research represents a major step forward for the DM1 field,” said Beatriz LlamusÃ, co-founder and chief scientific officer of ARTHEx Biotech.
“For the first time, we are seeing a clear connection between improvement of molecular alterations in the brain and meaningful functional improvements in a DM1 model. Importantly, this was achieved through systemic delivery using our BOOST-ON platform, which has the potential to simplify treatment while addressing the full spectrum of the disorder.”
In the preclinical studies, ARTHEx’s proprietary lipid-conjugated antimiR-23b demonstrated:
Systemic brain delivery, crossing the blood-brain barrier following intravenous administration
Mechanistic engagement, increasing MBNL1/2 protein levels and reducing toxic DMPK transcripts in the brain
Correction of disease biology, including partial rescue of splicing abnormalities across multiple brain regions in an animal model that express a long tract of CTG repeats in the range on congenital, which supports that ATX-01 could be beneficial for congenital patients
Functional improvement, with normalization of behavioral alterations such as exploratory activity
Favorable tolerability, with no significant toxicity or neuroinflammation observed
The findings suggest the potential for a disease-modifying approach that addresses both muscular and neurological aspects of DM1.
“This publication further strengthens our conviction in the ArthemiR programme,” said Frédéric Legros, executive chairman and CEO of ARTHEx Biotech.
“While our clinical efforts have been focused on addressing the systemic and muscular manifestations of DM1, these new preclinical results highlight the potential to also impact central nervous system involvement—an area of significant unmet need. Importantly, this work reinforces the breadth of our approach as we continue advancing the ArthemiR trial, with the goal of delivering meaningful benefits across the full spectrum of DM1.”
ATX-01 is designed to inhibit microRNA-23b (miR-23b), a natural suppressor of muscleblind-like (MBNL) protein expression. In individuals with DM1, loss of functional MBNL activity occurs through two complementary mechanisms: first, upregulation of miR-23b reduces MBNL protein expression; and second, expanded toxic DMPK mRNA sequesters MBNL proteins within the nucleus. The resulting depletion of available MBNL proteins leads to widespread RNA mis-splicing (spliceopathy), which underlies the multisystem symptoms characteristic of DM1. These symptoms primarily affect the skeletal muscle, cardiac, and central nervous systems, though additional organ systems may also be involved. Disease onset most commonly occurs during adolescence, and DM1 is associated with progressive disability and reduced life expectancy.
ARTHEx is currently advancing ATX-01 in the phase I/IIa ArthemiR study and continues to work closely with regulatory authorities, clinical investigators, and patient advocacy groups to accelerate progress.