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 (August 2023):
- 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”.
- 2020-2022 dosing (rodent) study: the CRP dosing study (funds pre-allocated by endParalysis at the end of 2019) has mainly tested dose responses of CRP to see if a higher dose can lead to an additional functional improvement, after chronic spinal cord injury. However, the preliminary progress report relates very encouraging results.
Patient enrolment/clinical trials/ next translational steps:
– We hope to receive the final results of the 2020 CRP dosing animal study funded by endParalysis soon.
– 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. The result of this study is not known yet.
– 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.