Clene presents preliminary data on CNM-Au8 in Rett Syndrome

Clene presented new, preliminary data demonstrating the potential of CNM-Au8 as a treatment for Rett Syndrome. Karen Ho, Ph.D., Clene’s vice president of translational medicine, unveiled the data in oral and poster presentations on June 19th at the International Rett Syndrome Foundation 2024 Annual Meeting in Westminster, Colorado. The presentation was titled, “CNM-Au8, a Candidate First-in-Class Nanotherapeutic for Treatment of Rett Syndrome.” Rett Syndrome is a severe, rare pediatric neurologic disorder caused by mutations in the X chromosome-linked gene, methyl-CpG binding protein 2. The disorder primarily affects females, with an incidence of ~1:10,000 live female births. Children with mutations in MECP2 develop normally until about 6 months of age, after which they exhibit a regression in acquired skills and begin to display a wide range of neurological and developmental impairments that include hand-wringing with loss of purposeful hand movement, abnormal gait, respiratory dysregulation, autism spectrum features, motor dysfunction, loss of verbal communication skills, seizures, and Parkinson-like features. Microcephaly and white matter loss are pathological features of the Rett brain. There is currently only one approved drug for the treatment of Rett Syndrome, trofinetide, which was approved by the U.S. Food and Drug Administration in 2023. CNM-Au8 is an orally administered, catalytic nanotherapeutic that targets energy metabolism via mitochondria in nervous system cells, including neurons and oligodendrocytes, to enhance neuronal survival and function as well as to support remyelination. To date, Clene has focused on the development of CNM-Au8 for the treatment of ALS and MS. The novel mechanism of CNM-Au8, with its catalytic ability to bolster mitochondrial function to aid in the survival and function of neurons, as well as the remyelinating properties of CNM-Au8, led Clene to also consider Rett Syndrome as a possible indication for treatment by CNM-Au8. The project was conducted in collaboration with Dr. Kathrin Meyer, formerly of Nationwide Children’s Hospital in Columbus, Ohio, now Chief Scientific Officer of Alcyone Therapeutics, and her former postdoctoral researchers, Drs. Meysam Ganjibakhsh and Andrea Sierra Delgado. Dr. Delgado was former Chief Research Associate in the Meyer lab and is now Research Assistant Professor at the University of Missouri. The study’s main preliminary findings are: Statistically significant improvement in neuronal health, neuron survival, and neurite lengthsin an in vitro model of Rett Syndrome, and; Improvements in the mitochondrial respiration deficits associated with Rett patient-derived astrocytes with CNM-Au8 treatment in vitro, with full rescue of both basal and ATP-linked respiration observed in one Rett line, and partial rescue observed in a second Rett line at one concentration of CNM-Au8 treatment for 24 hours. All statistical analyses were done using one-way ANOVA, and all conditions were performed with a minimum of three replicates.