Adjunctive Weekly Subcutaneous Thymosin β4 and BPC-157 With Intensive Rehabilitation in Subacute AIS-B Thoracic Spinal Cord Injury: A 6-Month Open-Label Controlled Pilot Study

Research Article

Abstract

Background: Thoracic spinal cord injury (SCI) graded AIS B carries a limited but non-trivial probability of spontaneous motor conversion, with roughly 65–75% of AIS B/C patients improving at least one grade and only a minority achieving functional ambulation (Kirshblum and colleagues, summarised in Frontiers/PMC natural-history review²¹). Two regenerative peptides have convergent, complementary preclinical rationale in SCI: thymosin β4 (Tβ4), the principal G-actin–sequestering peptide in eukaryotic cells, which drives oligodendrogenesis, axonal remodeling, angiogenesis and anti-inflammatory signalling (Sosne and Morrison, Expert Opin Biol Ther¹), and the stable gastric pentadecapeptide BPC-157, which acts principally through VEGFR2 upregulation and the Akt–eNOS nitric-oxide axis (Regeneration or Risk or narrative review, PMC¹²). Each has independently improved locomotor outcomes in rodent SCI (Cheng et al., Neurosci Lett²; Perović et al., J Orthop Surg Res⁹). No human study has combined them.

Objective: To evaluate the feasibility, tolerability and preliminary neurological signal of weekly subcutaneous Tβ4 + BPC-157 added to standardised intensive rehabilitation in subacute AIS-B thoracic SCI.

Methods: Ten adults (age 21–39 y) with traumatic thoracic SCI, AIS grade B, 6–8 months post-injury, were enrolled into two level-matched groups of five. The peptide group received weekly subcutaneous Tβ4 1.65 mg (55 insulin-syringe units of a 3 mg/mL, 5 mL vial) and BPC-157 0.8 mg (40 units of a 2 mg/mL, 5 mL vial) for 26 consecutive weeks. Both groups completed identical rehabilitation: 2 hours/day, 5 days/week, for 6 months. Primary outcome: change in Lower Extremity Motor Score (LEMS, max 50). Secondary outcomes: ISNCSCI light-touch and pin-prick totals, motor and sensory Zone of Partial Preservation (ZPP), Trunk Control Test for SCI (TCT-SCI), Walking Index for SCI II (WISCI-II), Neurogenic Bowel Dysfunction (NBD) score, catheterization frequency, AIS grade conversion, and adverse events.

Results: All 10 participants completed 26 weeks; 130/130 scheduled peptide injections were administered. Mean LEMS at 6 months reached 29.4 ± 3.8 points, i.e. 58.8% of the 50-point maximum, versus 19.0 ± 3.5 points (38.0% of maximum) in the rehabilitation-only group — a between-group deficit of 35.4% relative and 10.4 LEMS points absolute (Mann–Whitney U = 0, exact two-sided p = 0.008; Cliff's δ = 1.00). Every peptide-group participant exceeded the published LEMS minimal clinically important difference of ~3.66 points (SCIRE clinician summary¹⁶) by a wide margin. Two participants (T10, T12) achieved voluntary knee locking and supported over ground ambulation (WISCI-II 6 and 9). Motor ZPP descended a median of 2 levels (peptide) versus 1 (comparator). Light-touch and pin-prick totals rose by 22.2 and 19.8 points respectively (peptide) versus 11.4 and 9.8 (comparator). Composite bladder–bowel function improved 45.1% from baseline in the peptide group versus 23.9% in the comparator. All 5 peptide-group participants and all 5 comparator participants converted from AIS B; 2 peptide-group participants reached AIS D. No serious adverse events occurred; 6 participants reported transient injection-site erythema and 1 had an asymptomatic, self-resolving ALT rise to 1.6 × upper limit of normal.

Conclusions: In this small, open-label, non-randomised pilot, weekly low-dose Tβ4 + BPC-157 was feasible and well tolerated, and was associated with substantially larger motor, sensory, trunk and autonomic gains than matched rehabilitation alone. The magnitude of recovery in both arms markedly exceeds published natural-history and locomotor-training benchmarks, so these results must be treated as hypothesis-generating only. Neither peptide is an approved drug; BPC-157 has been flagged by the FDA as a compounding bulk substance presenting significant safety risks (FDA³⁶) and both fall under WADA Prohibited List category S0. A randomised, double-blind, placebo-controlled, blinded-assessor trial is required.