Fractional Reaction–Diffusion Modelling of Immune-Mediated Demyelination in Multiple Sclerosis Under IFN-Beta and Glatiramer Acetate Therapy


Enver A., AYAZ F., Yavuz M., Usta F.

Fractal and Fractional, cilt.10, sa.5, 2026 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 10 Sayı: 5
  • Basım Tarihi: 2026
  • Doi Numarası: 10.3390/fractalfract10050281
  • Dergi Adı: Fractal and Fractional
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, INSPEC, Directory of Open Access Journals, Academic Search Ultimate (EBSCO), Materials Science & Engineering Collection (ProQuest), Technology Collection (ProQuest)
  • Anahtar Kelimeler: continuous-time random walk derivation, dimensional consistency, distributed-parameter control, fractional reaction–diffusion systems, Mittag–Leffler memory
  • Gazi Üniversitesi Adresli: Evet

Özet

We propose a dimensionally consistent fractional spatio-temporal PDE framework for modelling immune-mediated demyelination in multiple sclerosis (MS). The system couples effector and regulatory T cells, M1/M2 macrophage polarisation, pro- and anti-inflammatory cytokines, oligodendrocyte dynamics, and time-dependent therapeutic controls withina unified distributed-parameter structure. In contrast to ad hoc replacements of integerorder derivatives by Caputo fractional derivatives, the fractional extension proposed here is derived from an underlying continuous-time random walk (CTRW) process with Mittag–Leffler-distributed residence times. This stochastic derivation yields a governing system in which a single commensurate fractional order (Formula presented.), together with a characteristic memory timescale (Formula presented.), ensures dimensional consistency and mass balance across all coupled components. The model is formulated as a system of nonlinear reaction–diffusion equations with cross-regulatory and multiplicative interaction terms governing immune amplification, cytokine feedback, and the demyelination–remyelination balance. Analytical interpretation shows how non-Markovian residence times induce Mittag–Leffler-type relaxation and thereby modify effective growth, decay, and stability properties. Numericalsimulations compare classical and fractional dynamics, revealing that memory-driven kinetics prolong effector T-cell and M1-macrophage activity, attenuate reparative M2 and oligodendrocyte responses, and extend the effective action of bang–bang therapy inputs representing IFN- (Formula presented.) and glatiramer acetate beyond their dosing windows. The results indicate that integer-order models may underestimate chronic inflammatory persistence and demyelination severity, while providing a mathematically and physically well-posed platform for memory-aware immune modelling and therapy evaluation in MS.