Notre financement recherche
Notre strategie de recherche
Notre processus de selection
Projets de recherche financés
La paralysie sera guérie un jour…
…mais nous n’en sommes pas encore là. Nous utilisons tous les fonds que nous recevons de manière ciblée, en visant une application humaine, pour les personnes atteintes de lésion médullaire
Comment garantissons-nous la rigueur scientifique ?
Le processus de sélection professionnelle ci-dessous garantit que les projets que nous finançons sont conformes à notre stratégie et rigoureux sur le plan scientifique.
Où va votre argent ?
Vous trouverez ci-dessous les détails des études de recherche sur les lésions de la moelle épinière que nous avons soutenues jusqu’à présent.
Notre stratégie de recherche
Notre action, notre focus
Nous avons actuellement trois piliers d’action :
- Influencer la recherche, informer -> Nous nous engageons auprès de la communauté scientifique pour promouvoir une recherche plus ciblée et informer les patients atteints de LME / les familles des dernières recherches curatives.
- Financer la recherche ciblée -> Nous finançons la recherche qui aborde des défis ou des obstacles bien définis à l’application des traitements et seulement si elle peut être appliquée aux personnes vivant actuellement avec une paralysie (LME « chronique »).
- Accélérer l’application sur les humains -> Nous travaillons pour accélérer le passage d’au moins une thérapie prometteuse du laboratoire à la clinique. Pour ce faire, nous faisons appel à des partenaires qui ont le même objectif que endParalysis, à savoir fournir des traitements curatifs aux patients le plus rapidement possible.
Nos directions de recherche
Recherche sur la réparation biologique pour la récupération fonctionnelle et sensorielle après une LME chronique, y compris :
- Réduction de la cicatrice gliale -> Suppression de la cicatrice (qui persiste au stade chronique de la blessure et empêche la repousse des nerfs). Ce traitement vise également à améliorer la plasticité neuronale afin que de nouvelles connexions puissent être établies et que le corps puisse réapprendre.
- Repousse des nerfs -> Faire repousser les axones (nerfs de la moelle épinière) à travers la lésion pour établir de nouvelles connexions et rétablir la communication entre le cerveau et les autres parties du corps et permettre des fonctions et des sensations naturelles et biologiques.
- Remplacement de tissus -> Remplacement ou réparation de moto-neurones ou d’autres composants endommagés, qui peuvent être nécessaires pour inverser complètement la paralysie.
Comment nous sélectionnons les projets de recherche à financer ?
Étape 1 : présélection
Une proposition de projet est présélectionnée par le conseil d’administration de endParalysis (EP) si :
- Le projet répond aux trois critères de sélection de la fondation (1. applicable aux lésions chroniques de la moelle épinière, 2. principalement biologique, 3. offrant un potentiel d’application humaine).
- La thérapie proposée semble être en accord avec les principales orientations de recherche et le portefeuille de traitements ciblés de endParalysis.
Étape 2: examen scientifique
La proposition est soigneusement examinée et évaluée par des scientifiques :
- Soit le comité consultatif scientifique d’endParalysis,
- Soit le comité consultatif scientifique d’une organisation partenaire (pour éviter tout conflit d’intérêts), ou
- Un certain nombre d’experts scientifiques sélectionnés (pour garantir une expertise très spécifique nécessaire à un projet donné).
Étape 3: validation finale
La validation finale se fait selon les étapes suivantes :
- Le CA d’endParalysis compile les évaluations scientifiques
- Il aborde les questions soulevées par les évaluateurs avec le laboratoire du chercheur.
- Une fois que toutes les remarques importantes ont pu être écartées/ clarifiées, et si la majorité des évaluations scientifiques finales recommandent le financement, le CA valide la proposition.
Les projets de recherche sur les lésions de la moelle épinière que nous avons financés jusqu’à présent
Introduction: MAJ juin 2022 : Cette section est en cours de construction et sera bientôt mise à jour.
Financement en cours (2018-2021)
CRP (CSPG Reduction Peptide) – to reduce the scar at CHRONIC stage – Dr. Yu Shang Lee – Pre-clinical stage (Animal studies - USA)
Background info:
The formation of an enduring glial scar near the injured site leads to poor nerve regrowth capacity and poor functional outcomes in chronic stages after SCI. Chondroitin Sulfate Proteoglycans (CSPGs) are the major components of this glial scar. The small peptide (a tiny organic compound) called CSPG Reduction Peptide (CRP) was designed by Dr. Yu Shang Lee’s lab (Cleveland Clinic – USA) to meet this need. The endParalysis started to support the translation of this potential therapy from the lab to the clinics (i.e. to humans) in 2018. The non-invasive character of the CRP (it can be applied by subcutaneous injection) is of great interest. CRP treatment, if proven effective, will, in principle, be easily applied to human patients and might constitute a very valuable alternative to other scar-alleviating therapies currently under development such as Ch’ase. Indeed, the latter treatment requires a specific and elaborate delivery method to safeguard its effectiveness as well as safety for the patient.
Latest update (Oct. 2021):
– 2018-2019 rodent study, after a first preliminary small study with a limited number of rodents, Dr. Yu Shang Lee’s lab carried out additional studies using more rats with a T8 chronic contusion SCI. The project, co-funded by the endParalysis foundation, aimed to determine the efficacy of CRP alone, of ISP alone, and of CRP + ISP (ISP is another peptide, developed in Dr. Jerry Silver’s lab, Case Western Reserve University). Various tests were conducted, including a combination therapy. Starting two-month post-SCI, the treated animals received the various peptides by daily subcutaneous injection during three consecutive months. Both CRP and ISP were administered at a low dose in this study.
The study showed that:
-
- CRP significantly improved bladder function and locomotor function (*)
- The results were not much improved or changed when adding up ISP (**).
- The test highlighted, on the other hand, that ISP alone did not enable any functional recovery of the rats at the CHRONIC stage (although it has been proven Dr. Jerry Silver’s lab to have a robust effect at the ACUTE stage).
(*) Abstract from the Lee lab’s report:”The study seems to show that CRP enhanced connectivity established across injury site and nerve sprouting below the injured site after treatment, as well as an improved function for both locomotion and bladder (the CRP-treated groups show less hyperactivity, better void efficiency, and lower voiding pressures)”
(**) Abstract from the Lee Lab’s report: “While there was a trend showing CRP+ISP works slightly better in improving BBB scores (BBB is a test of stepping function) than CRP alone, there was, overall, no significant difference between the CRP+ISP and CRP groups”.
– 2020-2021 dosing (rodent) study: the CRP dosing study (funds pre-allocated by endParalysis at the end of 2019) is mainly testing dose responses of CRP to see if a higher dose can lead to an additional functional improvement, after chronic spinal cord injury. This study suffered some delay due to the COVID-19 lockdown measures. However, the preliminary progress report relates very encouraging results. We expect the final report to be available by the end of 2021 and will share the conclusion on our website.
Patient enrolment/clinical trials/ next translational steps:
– We hope to receive the final results of the 2020 CRP dosing animal study funded by endParalysis by the end of February 2022
– Meanwhile, Dr. Yu-Shang Lee has been working with Dr. Brian Kwon to investigate the efficacy of CRP in a large animal model using mini-pigs T10 subacute stage injury model to test both locomotion and bladder function. The study progress has also been delayed by COVID-19 and results are expected in 2022.
– Next step for the CRP therapy will be conducting Pharmacokinetics and Safety/toxicity tests of CRP. Those are necessary for any therapy to go to spinal cord injury clinical trials.
Microcure and University Pre-clinical stage (animal studies- USA)
Background info:
Latest update (Nov. 2021):
Patient enrolment/clinical trials/next translational steps:
KN combined gene therapy- Blackmore Lab – Pre-clinical stage (animal studies- USA)
Background info:
Funds from endParalysis enabled a pilot collaboration between Dr. Murray Blackmore and Marquette University and Dr. Steve Perlmutter at Washington University to test a new gene therapy treatment for chronic spinal cord injury. The animal study, funded by the endParalysis foundation in 2020- 2021, aimed to advance the promising new gene therapy approach for improving axon growth after CHRONIC spinal cord injury. It is based on a recent discovery from Dr Blackmore’s lab that a combination of two transcription factors, Klf6 and Nr5a2 (KN), stimulates robust and highly reliable growth from corticospinal tract (CST) axons. The goal here was to push in the direction of translation by determining whether KN is similarly effective in a more chronic and clinically relevant model of spinal contusion in the laboratory of Steve Perlmutter at the University of Washington. For more info about the project and its selection, read this blog post.
Latest update (May 2022):
The treatment has shown promise in animal testing when applied acutely to a mild injury, raising the question of whether it could be similarly effective in more severe and chronic injuries. With support from endParalysis the Blackmore and Perlmutter performed a series of experiments to establish viral designs and surgical techniques to deliver the treatment to rats in the chronic stage of spinal cord injury. Using these pilot data the two labs were able to secure additional funding from the Craig H. Nielsen foundation for expanded testing of this approach to enhancing repair and functional recovery after chronic spinal cord injury.
This figure illustrates successful and widespread gene delivery to injured neurons when administered in the chronic injury condition. This is an important prerequisite for translational development of this approach.
Patient enrolment/clinical trials/next translational steps:
This therapy is still at pre-clinical stage. Various studies need to be conducted before it is tested on human subjects with a spinal cord injury.
PNN-i study- Dr Kwok- University of Leeds- UK (animal study for SCI, but this drug is already on the market for other conditions)
Background info:
PNNi refers to a molecule that is already on the market (used to treat a rare disease). It was recently tested by Dr Kwok / University of Leeds, as a potential therapy for spinal cord injury. In her animal studies, the drug has shown promising results when used at the acute (i.e. very early) stage of SCI. The molecule seems to neutralise the PNN (PeriNeural Net) as well as the scar, which both prevent nerves regrowth. The main advantage of this therapy, if results are confirmed and the side effects are manageable, is obviously a shorter path to the clinics, since the drug is already approved!
Latest update (Nov. 2021):
PNNi dosing study (including chronic SCI) by the Kwok Lab: this study was co-funded by the endParalysis foundation at the end of 2020 together with two other foundations: We thank the Marina Romoli Onlus (Italy) and Gusu2cure (USA) for accepting to fund this project with us. The animal study is ongoing. It is aimed to check if the PNNi molecule (an oral drug) works as well in chronic settings as in acute settings, and whether a higher dose is needed for chronic spinal cord injury. Also it will be scientifically checked what lowest possible quantity enables to keep the therapeutic effects intact while avoiding unfavourable side-effects. The first report regarding this study is positive, but the final report will only be received in 2022.
Patient enrolment/clinical trials/next translational steps:
For Spinal Cord Injury, this therapy is still at pre-clinical stage, with a clear objective to go to the clinics. Various studies need to be conducted before it is tested on human subjects with a spinal cord injury.
Financement passé (2015-2017)
CH’ASE IT: Chondroitinase and gene therapy for chronic SCI- PRE-CLINICAL stage (ANIMAL STUDIES - UK- NL)
Background info:
The application of a bacterial enzyme (a protein) called Chondroitinase, or Ch’ase, has repeatedly been proven to degrade the scar, to promote growth and to improve recovery in animal experiments. However, applying it to people is challenging. The goal of the project “CHASE-IT”, initiated by the International Spinal Research Trust (ISRT), is to make the Ch’ase therapy ready and safe for clinical application. It relies on an international collaboration between various researchers, among others in the UK and in The Netherlands. Recent experiments, using gene therapy models to deliver the enzyme, have moved the therapy closer to human application. The gene for Ch’ase is expressed in an active form in human cells and can be switched on and off to ensure an optimal and controlled delivery.
Latest update (Oct. 2021):
Two alternative gene delivery therapies have been developed/ are being tested :
a- The chondroitinase enzyme is delivered via a Lenti-virus vector (a virus made harmless and capable of carrying therapeutic genes). The consortium demonstrated this exciting new approach gave rise to improved walking and unprecedented upper limb function in rodent acute spinal cord injury models. See more information in this article and video and this Brain publication (August 2018). The same treatment was tested in a rodent chronic injury model at the end of 2018. The latest chronic trial has only shown modest results in terms of recovery and the current focus of the researchers is to combine treatment with rehabilitation to improve. More work has yet to be carried out to obtain the expected functional efficacy.
b- The Ch’ase enzyme is delivered via an Adeno-associated viral (AAV) vector which has the advantage of already being used in other human treatments and would, therefore, allow easier access to clinical trials. Various AAV vectors were created by Verhaagen’s lab and tested but they need further adjustment to ensure that the vector can be totally switched off when needed, without any further leakage. Indeed, one issue researchers found with AAV vectors was a noticeable background expression of the chondroitinase in the “off” setting.
The first two rounds of studies were co-funded by the endParalysis foundation and Spinal Research in the UK up to 2019. The follow-up studies are funded by the Wings for Life foundation as of 2020. The current study specifically focuses upon applying Ch’ase on rodents with a chronic SCI and combining with physio therapy to improve functional results.
Patient enrolment/clinical trials/ next translational steps:
-The AAV vector, once optimized, will be tested in both acute and chronic SCI models (rodents).
– Discussions are ongoing to test the best version of the chondroitinase therapy on humans. This is, however, a long-term goal.
Contactez-nous
info@endParalysis.org
Fondation endParalysis
Cederlaan 135
5616 SC EINDHOVEN
THE NETHERLANDS/ Pays-Bas