NMD Pharma publishes new data on the role of ClC-1 inhibition in Charcot-Marie-Tooth in the Annals of Clinical and Translational Neurology
- Results from the ESTABLISH1 observational study confirms that neuromuscular junction (NMJ) dysfunction is an underappreciated disease characteristic in patients with Charcot-Marie-Tooth disease (CMT) types 1 and 2 affecting muscle function in patients
- Additionally, results from preclinical studies provide proof-of-mechanism for recovery of muscle function with ClC-1 inhibition using NMD670 in CMT mouse models
Preclinical studies have previously implicated NMJ transmission deficits in muscle dysfunction in CMT. This study describes results from ESTABLISH1, an observational clinical study in CMT Type 1 and 2 patients and healthy patients in the US and Denmark, which confirms that patients with CMT, regardless of genotype, have notable NMJ transmission dysfunction that correlates with disease severity.
In addition, the paper describes that the treatment of mouse models of CMT Type 1 (CMT1A) and CMT Type 2 (CMT2D) following partial inhibition of ClC-1 chloride channels and the application of nerve-stimulated muscle force, was shown to improve muscle contractile function with the addition of the novel small molecule ClC-1 inhibitor NMD670.
W. David Arnold, MD, Principal Investigator who led the international ESTABLISH1 observational study, commented: "With no currently approved therapies to provide a cure or alleviate symptoms, data from the ESTABLISH and preclinical studies represents a significant milestone in the development of a treatment. Here, the data shows that patients with CMT, regardless of genotype, are characterized by notable NMJ transmission dysfunction, and that the level of dysfunction directly correlates with the level of disease severity, further confirming the potential therapeutic value of ClC-1 inhibition to address the muscle weakness and fatigue associated with CMT.”
Thomas Holm Pedersen, Chief Executive Officer of NMD Pharma, added: "This data provides further evidence of the crucial role of neuromuscular junction dysfunction in CMT patients. The impaired connectivity between the motor neuron and skeletal muscle at the neuromuscular junction in CMT patients presumably occurs because the axons are in a process of degeneration or are newly formed or forming neuromuscular junctions from axons nearby degenerated connections. It is very promising that NMD670 improves muscle contractile function in animal models of CMT, and we have already started evaluating the effect of NMD670 in a Phase 2 clinical trial which we initiated in November 2024.”
The full manuscript is available online through the following link: Neuromuscular transmission deficits in patients with CMT and ClC‐1 inhibition in CMT animal models - Grønnebæk - Annals of Clinical and Translational Neurology - Wiley Online Library
On 18 November, NMD Pharma announced that it had dosed the first CMT disease patient in its Phase 2 clinical trial of NMD670. NMD Pharma has three ongoing global clinical trials investigating NMD670 across rare neuromuscular diseases characterized by a high degree of patient impact and need, including a Phase 2 study in adults living with spinal muscular atrophy type 3 and a Phase 2b study in generalized myasthenia gravis patients.
Further information on the study can be found here: Study Details | Safety and Efficacy of NMD670 in Adult Patients With Type 1 and Type 2 Charcot-Marie-Tooth Disease | ClinicalTrials.gov
- Exploring SynapTic ABnormaLitIeS in Hereditary neuropathies
Contacts
NMD Pharma A/S
Dan Brennan, SVP Corporate and Commercial Strategy
E-mail: [email protected]
ICR Healthcare
Mary-Jane Elliott / Ashley Tapp / Lindsey Neville
E-mail: [email protected]
Tel: +44 (0)20 3709 5700
About NMD Pharma
NMD Pharma A/S is a clinical-stage biotech company developing a first-in-class platform of small molecule therapies selectively targeting the skeletal muscle chloride ion channel (ClC-1) for the treatment of rare neuromuscular disorders and age-related neuromuscular diseases with high levels of patient unmet. The Company was founded on more than 15 years of muscle physiology research with a focus on regulation of skeletal muscle excitability under physical activity. NMD Pharma has built a world-leading muscle electrophysiology platform leveraging the in-depth know-how of muscle physiology and muscular disorders, small molecule modulators, enabling technologies and tools as well as in vivo pharmacology models for discovering and developing proprietary modulators of neuromuscular function. The Company has built significant clinical and development expertise as its programmes have progressed through the clinic. NMD Pharma has raised ~€155 million from investors including Novo Holdings, Lundbeckfonden BioCapital, INKEF Capital, Roche Venture Fund, and Jeito Capital. Find out more about us online at http://www.nmdpharma.com.
About NMD670
NMD670 is NMD Pharma's lead development program. It is a first-in-class small molecule inhibitor of the skeletal muscle specific chloride ion channel 1 (CIC-1). NMD Pharma has demonstrated that CIC-1 inhibition amplifies the muscle's responsiveness to weak signals, improving neuromuscular transmission and restores skeletal muscle function. This novel treatment approach has resulted in clinical evidence of CIC-1 inhibition in myasthenia gravis and preclinical evidence in spinal muscular atrophy, Charcot-Marie Tooth disease and sarcopenia. NMD670 has also been granted orphan-drug designation by the U.S. FDA for treatment of gMG.
About Charcot-Marie-Tooth disease (CMT)
CMT encompasses a group of hereditary sensory and motor neuropathies that cause damage to peripheral nerves and their neuromuscular junction. Damage caused by CMT worsens slowly over time and can result in substantial reductions in mobility, independence and quality of life due to muscle weakness, fatigue and atrophy across skeletal muscle groups such as the legs, feet, arms, hands and potentially leading to diaphragm weakness and paralysis. CMT is often broadly grouped into demyelinating (CMT type 1) and axonal (CMT type 2) based on nerve conduction studies, but there are more than 160 subtypes of CMT based on their genetic causes, clinical features and progression patterns. CMT affects approximately 136,000 individuals in the United States and 3.2 million worldwide, with first symptoms typically appearing during adolescence or early adulthood.
