Armatus Bio to Lead Development of CMT1A Gene Therapy

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by Patricia Inácio, PhD |

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Armatus Bio will now further develop a potential gene therapy for Charcot-Marie-Tooth disease type 1A (CMT1A), aiming to conduct clinical trials.

According to a press release from the CMT Research Foundation, which has been funding this therapy’s preclinical development, Armatus is in the process of licensing the gene therapy, which will be renamed as ARM-101.

The decision follows promising results from a two-year study using a mouse model of the disease.

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“ARM-101 is a promising therapeutic candidate with the potential to make a significant difference in many lives. These new data will enable us to attract investments to accelerate our development efforts, with the goal of reaching those who need it as soon as possible,” said Michael Triplett, PhD, co-founder, president, and CEO of Armatus.

The early steps of the gene therapy’s development were led by Kleopas Kleopa, MD, at the Cyprus Institute of Neurology and Genetics, along with Scott Q. Harper, PhD, at Nationwide Children’s Hospital in Columbus, Ohio.

CMT1A is usually caused by an extra copy of the PMP22 gene, leading to excess levels of PMP22 protein and abnormal myelin, the fatty substance that surrounds nerve fibers and is important for sending electrical signals throughout the nervous system.

The gene therapy was designed to reduce the levels of PMP22 protein, which is believed to prevent symptom onset and potentially rescue nerve damage in people with CMT1A.

The researchers first identified the best DNA sequence to target the PMP22 gene in lab-grown cells. They then used adeno-associated viruses, which are modified in the lab to not cause disease, as delivery vehicles and injected the gene therapy into the cerebrospinal fluid (the fluid surrounding the brain and spinal cord) of mice.

Results showed that compared with untreated mice, those given the gene therapy had a marked reduction in the levels of PMP22 in peripheral nerves, which send sensory and motor information from the brain and spinal cord to the rest of the body.

Further microscopy analyses revealed that the gene therapy eased demyelination (loss of myelin), a hallmark of CMT type 1.

Nerve function, strength, and balance improved significantly in the animals given the gene therapy, often to levels similar to mice without the CMT1A-causing mutation.

The benefits of the gene therapy were seen in young mice and in older animals already with significant loss of strength and balance.

After these encouraging results, and with additional funding from the CMT Research Foundation, the researchers conducted further experiments, which included longer treatment duration, assessment of immune response to treatment, and evaluation of a potential biomarker for CMT, called neurofilament light chain (NfL). NfL levels are typically higher upon nerve cell damage, making it a potential biomarker for nervous system disorders.

According to the CMT Research Foundation, every parameter measured continued to support the benefits of the gene therapy and its potential for testing in future clinical trials.

“Two and a half years after beginning discussions about this project with Dr. Kleopa, the therapeutic is showing strong results consistent with a viable treatment for CMT1A,” the release stated.