Our strategy & funding

Our research strategy

Our selection process

Research funded so far

Spinal cord injury will be cured…

…but we are not there yet. We use all funds we receive in a targeted way aiming for human application, for people living with SCI

How do we guarantee scientific rigour? 

Our professional selection process below ensures that the projects we fund are in line with our strategy and scientifically rigorous

Where does your money go?

Below you can see the details of the spinal cord injury research studies we have supported so far.

Our research strategy 

What we do, our focus

We currently have three pillars of action:

  • Influence Research, Inform -> We actively engage with the scientific community to promote more targeted research & inform SCI patients / families about latest curative research
  • Fund Target-Driven Research -> We fund research that addresses well-defined challenges or obstacles to translation of treatments and only if it can be applied to people currently living with paralysis (“Chronic” SCI)
  • Accelerate Human Translation -> We are taking steps to fast track at least one promising therapy from the lab to the clinic. We do this through partners who have the same goal as endParalysis – getting curative treatments to patients as soon as possible.          

Our research directions

Research towards biological repair for functional & sensory recovery after chronic SCI, incl.:

  • Scar reduction -> Remove the scar (that persists at the chronic stage of the injury and prevents nerves regrowth). This also aims to enhance neural plasticity so new connections can be made and the body can re-learn
  • Nerve regrowth-> Get axons (nerves in the spinal cord) to regrow across the lesion to make new connections and restore communication between the brain and other parts of the body and enable natural, biological functions & sensations.
  • Tissue replacement-> Replacing or repairing motor neurons or other components that have been damaged and might be needed for reversing paralysis fully.                                                          

How we select spinal cord injury research projects for funding 

Step 1: pre-selection

 

A project proposal is pre-selected by endParalysis (EP) board if:

  • the project fits the foundation’s three selection criteria (1. Applicable to chronic spinal cord injury, 2. Mainly biological, 3. Offering a potential to go to the clinic).
  • the proposed therapy appears to be in line with endParalysis key research directions and targeted portfolio of treatments  
Step 2: scientific review

 

The proposal is carefully reviewed & assessed by scientists:

  • either endParalysis scientific advisory committee, or
  • the scientific advisory committee of a partner organisation (to avoid conflict of interest), or
  • a number of selected expert scientists (to guarantee a very specific expertise needed for a given project)
Step 3: final validation

 

The final validation occurs as per the following steps:

 

  • EP board compiles the scientific reviews
  • They address the questions raised by the reviewers with the researcher’s lab
  • Once all important remarks can be dismissed through clarification, and IF the majority of final scientific assessments do recommend to fund, EP board validates the proposal.

 The spinal cord injury research projects we have funded so far 

 Update: August 25th, 2023 (partial update)

Current funding  (2018-2022)

CRP (CSPG Reduction Peptide) – to reduce the scar at CHRONIC stage – Dr. Yu Shang Lee – Pre-clinical stage (Animal studies - USA & UK)

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 non-invasive character of the CRP (it can be applied by subcutaneous injection) is of great interest. CRP treatment, if proven effective, would 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. The endParalysis foundation and partners supported various animal studies to check the robustness, replicability and safety of the CRP therapy in order to advance it towards human trials

 

Latest update (October 2023):

  • 2022-2023 CRP replication + combination study (Ronaldo Ichiyama’s lab, Leeds, UK): This animal study was co-funded by endParalysis and partners in 2022. The experiment was meant to check whether the behavioural improvements seen by the animals treated with CRP could be replicated by another lab, and whether they could be enhanced by the electric stimulation of the cord. E-stim through an implanted stimulator has repeatedly been shown to (slightly or significantly) improve behavioural outcomes in a number of human subjects by “awakening” the spinal cord neural connections that had become “dormant” as a consequence of the injury.
    Unfortunately, the effect of the CRP peptide was not proven by this study: there was no significant difference between groups treated with e-stim only and the groups treated with E-stim+CRP.

  • 2020-2022 CRP dosing study (Yu Shang Lee’s lab, Cleveland Clinic, USA): funds were pre-allocated by endParalysis and partners at the end of 2019 for testing dose responses of CRP. The goal was to confirm previous outcome and to see if a higher CRP dose could lead to additional functional improvement, after chronic spinal cord injury. Dr Yu Shang Lee reports “We have demonstrated the efficacy of CRP treatment to repair chronic SCI by improving locomotion (in the first progress report) and lower urinary tract function. In anatomical study, we also showed the CRP treatment can reduce glial scars and enhance the sprouting of serotonergic fibers that may leading to the functional recovery”.

  • 2018-2019 rodent study (Yu Shang Lee’s lab, Cleveland Clinic, USA): 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 endParalysis in 2018, 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 by Dr. Jerry Silver’s lab to have a robust effect at the ACUTE stage).

     

Patient enrolment/clinical trials/ next translational steps:

Over the period 2020-2023, endParalysis’ partner (Niall’s foundation - UK) funded independent CRO (Contract Research Organization) testing of CRP including pharmacodynamics (PD: studying the action of the drug on the organism) and pharmacokinetics (PK: studying the effect the organism has on the drug). These tests are necessary for any therapy advancing to human trials. The various in vivo and in vitro experiments carried out by the CRO have unfortunately failed to show a robust reach and effect of CRP when delivered subcutaneously.

However, a study carried out by  Dr. Brian Kwon (Canada) and funded by the DoD (Department Of Defense, USA) is currently testing the CRP in a larger animal model (mini-pigs with a T10 subacute spinal cord injury), using an intrathecal administration. We are looking forward to the results of the latter study. 

 

siFi2 therapy by MicroCures & USU University - Pre-clinical stage (animal studies- USA)

Background info:

The over-expression of FL2 (an inhibitory protein) after spinal cord injury results in inhibition to axon growth. Preclinical research suggests that siFi2 (a drug developed by the US biotech company MicroCures) can silence FL2 activity and thus trigger regeneration and reattachment of axons at the site of injury. This therapy is based on protein knock-down and enhances the body’s intrinsic healing processes. 

Latest update (October 2023):

Following the promising functional improvement observed in previous acute trials, endParalysis and partners have asked MicroCures and USU (Uniformed Services University of the health science – Maryland, USA)  to test the siFi2 therapy in rats with chronic injuries (endParalysis foundation co-funded this project through a research grant in 2021). The results of the study, as shared in October 2023, are encouraging. The experiment showed that the treatment is also effective at a later stage of the injury with improvements in both the BBB score (walking and stepping test for rodents) and the gait of the treated animals, when compared to the control group.

 

Patient enrolment/clinical trials/next translational steps:

This study is still at pre-clinical (animal testing) stage. However, we consider it to be a  promising therapy. The therapy will have to be further replicated in another lab, tested on a bigger number of animals in order to show robust effects and possible translation to the clinics.

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 at 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 (August 2023):

PNNi dosing study (including chronic SCI) by the Kwok Lab: this study was co-funded by the endParalysis foundation (2020-2022) together with two other foundations, i.e. the Marina Romoli Onlus (Italy) and  Gusu2cure (USA). The purpose of the study was to check the efficacy of the treatment at the chronic stage of SCI, and to determine the minimum dosage needed to reach a significant level of functional recovery. The study has proven that the molecule does indeed enable a clear functional recovery level in rats, even long after their initial injury, which is a very good outcome. PNNi molecule is used to treat people with a rare-disease and is thus suitable for clinical use. However, the latest study also showed that the dosage needed to achieve significant functional recovery in rats is higher than the one currently authorized on the market. Before going to human trial for use in spinal cord injury, it is necessary to finetune the treatment, either by increasing its efficacy so that it can be made effective at the authorized dosage or by addressing concerns of potential side effects and gaining regulatory approval for use at higher doses. 

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 and optimisation of the molecule need to be conducted before it is tested on human subjects with a spinal cord injury. 

 

Past funding  (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. Meanwhile, additional animal studies are being conducted and are funded by Wings For Life. For the latest update on this line of research, see our Research Overview page, here.

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