Product name
Mutant peptide from Clostridium botulinum stimulates Axon RegenerationSummary
A mutant exoenzyme from Clostridium improves axonal growth without affecting glial cells.Organization name
ipal GmbHProfile
Scientists from University Hospital Hannover and Charité Berlin have developed a mutant of an exoenzyme from Clostridium botulinum with neurotrophic functions, C3bot-NF, as well as a short axonotrophic peptide, C3bot-Pep, which can be applied to improve axonal growth
- without affecting glial cells
- with increasing number of branches
- in nanomolar concentrations
With the fast progress in understanding axon regeneration and functional repair during the last years, clinical treatments that would partially repair a spinal cord injury become imminent.
C3bot-NF or its peptide fragments, like the mentioned C3bot-Pep, are new and very efficient stimulators for axon regeneration. Growth of axons treated with C3bot-NF in nmolar concentrations is promoted substantially compared to axons of untreated cells. Strikingly, C3bot-NF leaves glial cells unaltered. As glial cells form scars after injuries, they are formidable barriers to axonal regrowth. The selectivity of C3bot-NF for only promoting axons makes it a valuable tool for repairing neuronal lesions, e. g. in spinal cord and brain injuries.
C3bot-NF is the enzyme deficient mutant of C3 exoenzyme from Clostridium botulinum, not-related to the neurotoxins. C3 proteins inhibit the intracellular Rho family proteins, which are involved in the interaction of the cytoskeleton with intracellular membranes and the extra cellular regulation of the actin cytoskeleton.
Preclinical studies with C3 enzymes have shown its capacity to induce extensive nerve regeneration in rats with spinal cord lesion.
Furthermore, C3 stimulates the growth of glial cells to the same extent as of neurons, so that scars in the region of the neuronal lesion are also promoted. Due to the promoted formation of scars, axons are hindered to grow over longer distances. These aspects make C3 a more disadvantageous tool for spinal cord repair or the repair of neuronal lesions in general.
C3bot-NF (C3botaa154-182) is a mutant of the C3 enzyme devoid of any enzyme activity to inhibit the Rho proteins.
It could be shown that C3bot possesses an additional axonotrophic function independent from its enzymatic activity. Peptides of C3bot, comprising the region of C3bot responsible for these axonotrophic effects, could be identified by immunoblotting and analysis of changes in the synaptic input of hippocampal neurons.
Incubating hippocampal neurons with 25 nM and 50nM C3botaa154-182 (C3bot-Pep) enhanced the overall axonal length as well as the number of branches by 40 - 50 %. Segment order analysis revealed an enhanced formation of branches, starting from the 4th order up to the 10th order.
The morphological changes elicited by C3bot-Pep was studied by quantifying the number of synaptophysin-expressing terminals on proximal dendrites of hippocampal neurons. The treatment with C3bot-Pep produced a significant increase of synaptic terminal numbers (about 30%).
International patent applications have been filed. Additional information is provided in the attached pdf.
The product is offered by IPAL.
Contact
IPAL GmbH
Dr. Petra Düx
petra.duex(at)ipal.de
About IPAL
The ipal GmbH patent agency assesses and markets the inventions of scientists in the area of Life Sciences and Physics & Engineering from Charité-Universitaetsmedizin (University Medicine), Robert Koch Institute, Deutsches Herzzentrum (German Heart Institute), Bundesanstalt für Materialpruefung (BAM - Federal Institute for Materials Research and Testing), the Zuse Institute as well as the Paul Ehrlich Institute, Langen and the Jacobs University Bremen. IPAL provides all of the services necessary - from the assessment of patentable technologies to a comprehensive patent protection all the way to the evaluation of sales returns potentials on the market and successful commercialisation through the use of licensing agreements.
Description File
02063_C3bot_Axonotrophic_Peptide.pdf
print this page
