Proof of concept

- Initial Focus

CMT1A – A pathology with no effective treatment to date

CLM001 was developed to target Charcot-Marie-Tooth disease type 1A (CMT1A), the most common hereditary peripheral neuropathy, characterized by progressive motor disorders beginning in childhood.

CMT1A is caused by a duplication of the PMP22 gene, leading to the overexpression of the PMP22 protein. This disrupts normal myelin formation and results in progressive peripheral nerve degeneration.

To date, no therapy has demonstrated clinical efficacy, and millions of patients are still awaiting a curative solution.

Non-clinical studies were conducted in two animal models of Charcot-Marie-Tooth disease type 1A (CMT1A).

These models carried multiple copies of the human PMP22 gene — mimicking the molecular and neurological characteristics of CMT1A.

Three key outcomes were observed after 12 weeks of treatment, demonstrating the therapeutic efficacy of CLM001.

+120% improvement in Motor Nerve Conduction Velocity (MNCV)

Observed after 12 weeks of treatment, confirming earlier findings from a previous 8-week study in younger animal models.

Up to 218% improvement in nerve conduction speed

Recorded in the most severely affected models (homozygous), indicating a strong therapeutic response in advanced disease stages.

Normalization of balance and motor coordination

Demonstrated through the beam balance test, reinforcing the functional benefits of the treatment.

Five major therapeutic effects were identified:

Reduction of oxidative stress

Both in vitro and in vivo, helping to protect nerve cells.
Reduction of endoplasmic reticulum (ER) stress

Supporting normal cellular function and protein folding.
Upregulation of PMP22 and MPZ

Two essential proteins involved in the formation and maintenance of the myelin sheath. Although CMT1A results from a duplication of the PMP22 gene, CLM001 appears to restore a more functional and balanced expression of PMP22.
Improved myelination

Demonstrated by a significant decrease in the G-ratio. A lower G-ratio suggests a thicker and healthier myelin layer, which is critical for proper nerve signal conduction.
Reduction of inflammation

Helping to create a healthier environment for nerve repair.

Microscopic proof of CLM001’s regenerative potential

Throughout these studies, no hepatic, renal, or systemic toxicity was observed.

Nano-Cur treatment significantly improved motor nerve conduction velocities (MNCVs), grip strength, and gait stability in both animal models.

Electrophysiological studies showed increased compound muscle action potential (CMAP) amplitudes, indicating better neuromuscular transmission.
Histological analysis confirmed a reduction in myelin abnormalities, supporting remyelination and axonal repair.

Supported by over eight years of research, these robust and reproducible findings form a solid foundation for clinical development.