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Botulinum neurotoxin type A for recovery from paraplegia after complete spinal cord lesion in a murine model

Country of Origin: Italy
Reference Number: TOIT20161115001
Publication Date: 17 November 2016

Summary

An Italian research group has developed a new therapeutic treatment based on the Botulinum neurotoxin type A (BoNT/A) to recover spinal trauma: a single spinal administration of BoNT/A after the traumatic event decreases inflammation, confers neuroprotection, preserves neurons from cell death and promotes regeneration leading to a complete recovery from paralysis and restoration of sensitivity.The Italian researchers are looking for partners for financial, technical and research cooperation.

Description

An Italian research team is focusing its research on pain transmission and inflammatory and chronic pain modulation, achieving important and innovative results in this field: a) use of toxins of bacterial origin, b) new drugs with new therapeutic use, c) knock-out or transgenic mice for specific proteins involved in nociception or that reproduce a genetic pathology. Three main goals are pursued: 1) study the mechanisms that rule the information along the nervous system appointed to pain transmission and control, 2) investigate the degeneration processes associated to neuropathies, 3) identify new pharmacological treatments in a therapeutic perspective.
The recent studies have led the Italian group to analyzing the Botulinum neurotoxin type A (BoNT/A), a potent biological toxin widely used in clinical practice for treatment of various disorders such as dystonia, including muscle spasticity, headaches and overactive bladder disorders. Over the course of more than 20 years, the therapeutic spectrum of BoNT/A has been successively expanded. Due to its high efficacy, duration of action and satisfactory safety profile, it has been used empirically in a variety of neurological, otolaryngological, ophthalmological, urological, gastrointestinal/proctological disorders, cosmetics, and pain.

In their recent studies, the Italian researchers have demonstrated that BoNT/A is able to contrast neuropathic pain (Nep) caused by peripheral nerve injury, and have patented a novelty in the treatment for spinal injuries and symptoms associated with them, from pain to paralysis. The invention demonstrates that, in a mouse model, BoNT/A is an efficacious treatment for a complete recovery from paralysis (paraplegia/tetraplegia) and restoration of sensitivity. Behavioural analysis have evaluated motor function, spinal reflex and pain response after BoNT/A administration.
Motor evoked potentials have indicated the regeneration degree induced by BoNT/A. Immunohistochemical and molecular assays revealed BoNT/A long-lasting effect, reduction in astroglial scar, apoptosis, inflammatory events and remyelinization.

The Italian group is looking for 3 kinds of cooperation:
- Financial support to improve R&D and cover the patent costs (i.e. business angels);
- Technical cooperations with pharmaceutical and biotech companies to improve the compound vehicle (device, volume/concentration, etc) and for sharing skill and resources (i.e the pharmaceutical company should be able to provide the researchers with the toxin).
- research cooperation: the ideal partner is able to transfer technology from animals to human (clinical trials)

Advantages and Innovations

A new therapeutic use of a molecule (BoNT/A) already widely used in clinical practice greatly reduces the time for translation to patients because kinetic, toxicity and dose/response curve are known. Furthermore, there are already several commercial formulations for the administration of BoNT/A. 
It is certainly analgesic/anti-inflammatory and it prevents neuropathic pain, all of which are symptoms associated with spinal cord injury (SCI).
Furthermore, there are not side effects at therapeutic doses.

Stage Of Development

Project already started

Requested partner

The Italian group is looking for 3 kinds of cooperation:
- Financial support to improve R&D and cover the patent costs (i.e. business angels);
- Technical cooperation for sharing resources and skills; i.e. the researchers would like to cooperate with pharmaceutical and biotech companies both to obtain the toxin and to implement the compound vehicle (device, volume/concentration, etc).
- research cooperation: the ideal partner is able to transfer technology from animals to human (clinical trials)

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