The invention demonstrates that Botulinum neurotoxin type A (BoNT/A) is an efficacious therapeutic treatment after 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 (paraplegia/tetraplegia) and restoration of sensitivity.
TECHNICAL ISSUE: Traumatic spinal cord injuries (SCI) cause sensorimotor function loss because the physical insult destroys the nervous tissue, interrupting the flow of information to and from the brain. SCI induces paraplegia or tetraplegia and it represents a dramatic health and social challenge that needs urgent attention by the medical and scientific community.
GLOBAL INCIDENCE and COSTS of SCI: 10,5 every 100,000 people/year, it was estimated 768,473 new cases for year in the world. These data give an idea of the vastness of the problem with a huge economic and social impact (9.7 billion dollars - Centres for Diseases Control and Prevention, U.S.A.).
MAIN CAUSES of SCI: road, domestic, sports, weapons and at work accidents.
Current Technology Limitations
No care or drugs are able to restore the fully motor funtionality in SCI patients, currently.
Regenerative therapies in preclinical researches and clinical trials:
Stem cells (poor effective with high risks)
Therapies of extracellular matrix degradation (condroitinase ABC – poor effective)
Two therapies combination (1+2) (limited results)
Electrostimulation therapies (expensive – long-term and limited improvements)
Robotics (exoskeleton – physiotherapic aspects)
The wide clinical use, especially neurological and muscular, the great commercial diffusion (the most important BigPharma: Allergan, Merz, Ipsen), the well-known pharmacology, its safety, its long-lasting action make the BOTULINUM NEUROTOXIN SEROTYPE A a potentially successfull biomedical application also for the proposed pathology (the spinal cord injury), able to reach, effectively and in short-term, a critical mass.
In absence of competitors (no approved and effective treatments exist in the SCI therapy), the invention could be placed in a position of uniqueness, reflecting once again the exceptional nature that characterizes this biological compound.
The product is READY for USE.
The BOTULINUM NEUROTOXIN SEROTYPE A is considered the landmark of the successfull translational research.
Our Technology and solutions
PROPOSED SOLUTION: single spinal administration of BOTULINUM NEUROTOXIN TYPE A (BoNT/A) within few hours (acute phase) from spinal trauma:
1- it is NEUROPROTECTIVE. BoNT/A protects from cellular death the neural cells not directly involved in the impact.
2- it REDUCES the glial scar formation and inflammation which hamper the growth and formation of new connections brain-spinal cord-muscle.
3- it FACILITATES the nervous regeneration (new stem cells)
4- it RESTORES locomotion and sensitivity after complete spinal lesion and it PREVENTS muscular atrophy.
BoNT/A is the biologic drug with the greater number of clinical applications on label and off label. When injected, BonT/A is able to develop a long-lasting therapeutic action (in human, up to 6 months). Doses, safety and toxicity are already known and different commercial drugs exist (Botox – Allergan; Dysport- Ipsen; Xeomin – Merz).
Clinical and Industrial leads.
Starting from the statement that the paralysis due to spinal cord lesions is currently untreatable, the first potential and great advantage will be the spinal regeneration and the motor recovery.
It’s about a second therapeutic use, therefore it is well-known toxicity, doses and therapeutic- and side-effects. The use in humans is approved (FDA, AIFA) for different neurological, muscular and dermatological pathologies; as well as BoNT/A is utilized off label for several clinical uses which employ commercial formulas (BOTOX® Dysport®, Vistabex®, Xeomin®).
The animal testing (preclinical results) for the new therapeutic use is already carried out and the effectiveness demonstration, in spinally contused mice with complete hindlimbs paralysis, published (Vacca et al. Toxins, 2020). The utilized doses (15 picograms/mouse), with therapeutic effect, haven’t toxicity, are safe and lower than those used in clinical therapy (100U Botox ῀ 4,8 nanograms/human).
Thanks to its biological action a single treatment (a single dose administration) is able to have a therapeutic activity from 2 to 6 months, in consistent manner, avoiding countinuing and repeated administrations.
The first studies have been object of the international (WO2016170501A1) and USA (Application N. 16/252,972) patent. The preclinical tests were carried out and validated (publication on the international scientific journal Toxins (Toxins 2020, 12(8), 491).
Last steps towards the market
- Phase 1: strengthen the results
> 6 MONTHS: To find investors and co-workers for clinical trials
> 18 MONTHS: New preclinical data with the commercial compound, Botulinum neurotoxin test in human nervous cells assay, Regeneration test (animal model) during chronic phase of spinal cord injury
- Phase II: clinical trials
> 12 MONTHS: Beta test: clinical trial phase IIB (small number of patients)
> 18/24 MESI: Clinical trial phase III: controlled randomized study (thousand patients) in different scientific centres in different countries.
> 6 MONTHS: New drug application ( (FDA, EMA, AIFA...)
- Phase III: approach to the market.