During embryogenesis, a small organ named Subcommisural Organ (SCO), located in the dorsal roof of the brain, differentiates and secrets a protein, the SCO-spondin, with potent activity on the neurogenesis.
All mammalians and several other species carry this organ from embryogenesis to the adult life, in contrary to humans where it regresses after birth and become vestigial in adults. In batracian, with for example salamander, SCO-spondin is still present at adult stage, conferring to the animal the capacity to regrow nerves after injury.
The interaction between glia and neurons is essential in development, function and repair of the central nervous system (CNS). Signaling of glia is critical for axonal guidance and synaptogenesis at early developmental stages, where glial cells play a prominent role in the pathology of neurodegenerative diseases such as Alzheimer and Parkinson diseases, dysmyelinating diseases, etc. The name “glia” encompasses a broad variety of cells including the secretory ependymal cells of the subcommissural organ (SCO).
Unlike lower vertebrates, human beings are unable to regenerate damaged or destroyed nervous cells.
Among the therapeutic approaches aiming to repair or to interfere with the progression of a disease, a particular attention was focused on the constituents of the extracellular matrix at the injury or degenerative site as well as compounds and proteins expressed during developmental processes which allow correct constitution of complex structures like the brain structure and the spinal cord.
In this context, SCO-spondin, a protein secreted early during the embryonic life by the specialized ependymocytes, is a promising candidate. In addition, this protein as well as its derived peptides, named NX peptides, have shown to have combined biological activities on nervous cells and in in vivo models of CNS disorders by promoting neuroprotection and neuroregeneration.
Our drug candidates, NX210 and analogs, meet criteria being highly desirable features for CNS damage treatment
- Our products are small peptides derived from the most conserved sequence of the thrombospondin repeat (TSRs) of the SCO-spondin, a naturally secreted protein with potent activity during neurogenesis
- TSRs are active domains involved in various context-dependent pathways and contributing in angiogenesis and axon guidance
Our drug candidates have multifunctional activities on neurons, incompassing:
Able to induce cell extension, neurite outgrowth and fasciculation
Our data demonstrates that NX210 is able to promote neurite fasciculation and axonogenesis in a dose-dependent manner [1; 2] as well as to protect neurons against insults .
In vivo in rodents NX210 has been shown to promote nerve fiber regrowth and the recovery of sensorimotor functions and in counteracting behavioral deficits in case of spinal cord injury (SCI) .
NX210 is a patented peptide deduced from the thrombospondin repeat domains (TSRs) of the SCO-spondin. This is a first-in class multi-functional agent able to prevents neural cell death and to promote neurite outgrowth. NX210 has been granted Orphan Drug Designation by European Medicine Agency (EMA) for the treatment of spinal cord injury. A Clinical Trial Application (CTA) for a phase I is now authorized by the french and belgian authorities.
In vivo regrowth of nerve fibers through the lesion site
60% of NX210 treated rats recover weight support and fore-hindlimb coordination (BBB >14)
Percentage of rats with a BBB score > 14 along the delay post NX210 treatment
BBB (Basso, Beattie and Bresnahan) Scoring is the reference method used to assess the motor function of rats. BBB over 14 means the return of toe clearance during stepping, predominant paw position, trunk stability, and tail position.