Central Demyelination Research Articles

Anti-Lactosylceramide antibody positive combined central peripheral demyelination emerging from long-standing juvenile-onset chronic inflammatory polyradiculoneuropathy; a report of two cases

Anti-Lactosylceramide (LacCer) antibodies are associated with neurological inflammation involving both the peripheral and central nervous system (PNS, CNS respectively), however, the documented number of cases is small. Uncertainty remains whether its positivity can identify a unique clinical entity. Here, we describe two anti-LacCer antibody positive cases, both with long histories (> 30 years) of teenage-diagnosed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). CNS lesions including the medulla oblongata were observed for the first time in adulthood. We suggest that this secondary progression of CNS lesions in juvenile-onset CIDP can be one of the characteristic features of anti-LacCer antibody associated neurological disorder.

MiRNAs as Valuable Diagnostic Biomarkers in Patients with Multiple Sclerosis

Multiple Sclerosis (MS) is an autoimmune condition caused by chronic inflammation of central nervous system and demyelination of neurons. At present, microRNAs (miRNAs) are recognised as a diagnostic and prognostic indicator of the diseases. But they are also a new and innovative goal in gene therapy. Therefore, the aim of this study is to find a simple, non-invasive, and valuable biomarker for early detection and potential treatment of MS. In the present study, 30 serum samples of patients with recurrent MS (recurrecy dettermined with McDonald's criteria) were obtained along with the 30 healthy samples. The qRT-PCR method was performed to evaluate the expression level of miR-155a, miR-146a, miR-34a, miR-143a and miR-373a in both groups. The results revealed that miR-155a and miR-146a were significantly upregulated while miR-34a, miR-143a and miR-373a were significantly downregulated in the patient group in comparison with healthy subjects. These results candidate these microRNAs with altered levels as potential diagnostic and prognostic markers in patients with MS, which may be involved in the therapeutic schedule for MS like microRNA replacement therapy in the near future.

Paraneoplastic Syndrome Presenting Combined Central and Peripheral Demyelination Associated with Anti-CV2/CRMP5 and Anti-NF186 Antibodies: A Case Report

The anti-CV2/CRMP5 antibody is a well-characterized biomarker of paraneoplastic neurological syndrome. The anti-NF186 antibody is a recently discovered antibody associated with central or peripheral demyelination. The co-occurrence of these two antibodies has not been reported. Herein, we report a case with anti-CV2/CRMP5 and anti-NF186 antibodies in a 57-year-old male presenting with progressive numbness and weakness in his four limbs. At first admission, the spinal cord MRI showed a cervical cord demyelinating lesion and electrophysiological examination showed a mixed demyelinating and axonal polyneuropathy. Anti-CV2/CRMP5 and anti-NF186 antibodies were both detected in his serum. Initially, the patient showed a positive response to IVIG and glucocorticoid treatment. However, the syndrome relapsed and mass lesions in lung and mediastinum were detected at second admission. This time the anti-NF186 antibody was not detected but the anti-CV2/CRMP5 antibody was still present. IVIG and glucocorticoid treatment was no longer effective. This case illustrated that paraneoplastic syndrome should be considered when diagnosing patients with central and peripheral demyelination, and that the anti-NF186 antibody may help distinguish a subset of patients who can benefit from immunomodulatory treatments.

MOG antibody associated with central and peripheral demyelination

MOG antibody disorder presenting as a combined central and peripheral demyelination (CCPD) is uncommon. CCPD has been associated with other primary demyelination syndromes such as multiple sclerosis, neuromyelitis optica or chronic inflammatory demyelinating polyneuropathy. Here, the authors describe the diagnosis and management of a 21‐year‐old female with historically sequential demyelinating plaques in her right thalamus, cervical cord, left optic nerve and electrophysiology suggestive of bilateral ulnar nerve demyelination.

Dysregulation of miR-193a serves as a potential contributor to MS pathogenesis via affecting RhoA and Rock1

Multiple sclerosis (MS) is one of the most common neurological diseases that cause chronic inflammation of the central nervous system and demyelination of the myelin sheath. At present, microRNAs (miRNAs) are considered not only a diagnostic and prognostic indicator of diseases but also a new goal in gene therapy. This study aims to find a simple, non-invasive, valuable biomarker for early detection and potential treatment of MS. In the present study, 30 patients with MS were included. The qRT-PCR method was performed to evaluate the expression level of miR-193a, RhoA, and ROCK1. Besides, western blotting was performed to determine the expression level of RhoA and ROCK1 at protein levels. Moreover, we aimed to clarify the possible correlation between miR-193a-5p and its-regulated target genes so that miR-193a-5p mimic was transfected into MS-derived cultured PBMSs, and the expression level of RhoA and ROCK1 were then evaluated by qRT-PCR and Western blotting. In the final step, the correlation between miR-193a-5p and clinicopathological features of patients was investigated. Results showed that miR-193a was decreased while RhoA and ROCK1 were up-regulated in PBMCs obtained from patients with MS compared to the control group. It was also revealed that miR-193a transfection reduced RhoA and ROCK1 expression at mRNA and protein levels. The results from the Chi-square analysis showed that down-regulation of miR-193a was associated with increased CRP level, CSF IgG positivity, and MSSS (Multiple Sclerosis Severity Score), suggesting miR-193a is a potential diagnostic and prognostic indicator. We implied that miR-193a could modulate RhoA and ROCK 1 expression in MS patients, in which its down-regulation leads to increased expression of RhoA and ROCK1 and poor prognosis of patients with MS. Therefore, miR-193a and its associated targets could serve potential prognostic, diagnostic, and therapeutic efficacy in MS patients.

Characterization of sperm motility and testosterone secretion in the taiep myelin mutant, a model of demyelination.

Presently, demyelinating diseases have been reported to affect the reproductive life of patients who suffer from them, but the progression of the alterations is unknown, especially in men. To better understand these effects, it is necessary to perform studies in animal models, such as the male taiep rat, which exhibits progressive demyelination of the central nervous system, altered kisspeptin expression at the hypothalamic level, and decreased luteinizing hormone, which could alter sperm quality and testicular diameter. Thus, the objective of the present study was to analyze the diameter of the seminiferous tubules, the sperm motility, and the testosterone levels of 90-day-old male taiep rats. The obtained results indicate that male taiep rats show an increase in testicular size accompanied by an increase in the diameter of the seminiferous tubules of the left testicle. There was also a decrease in progressive motility in sperm samples from the left epididymis of male taiep rats compared to the control group, with no changes in serum testosterone concentration. Therefore, we conclude that male taiep rats with central demyelination show altered testicular diameter and decreased motility in sperm from the left side. This type of studies serves as a basis for proposing possible reproductive strategies to improve the fertility and testicular function of men with demyelinating diseases of the central nervous system.

Assessment of Multiple Sclerosis Patients' Knowledge and Behavioral Practice Regarding COVID-19 in Saudi Arabia.

Background Coronavirus disease 2019 (COVID-19) is caused by a coronavirus subtype called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is crucial to control the spread of coronavirus by understanding the disease and practicing the measures adopted during the COVID-19 pandemic. Multiple sclerosis (MS) is a central nervous system immune-mediated inflammatory demyelinating disease. COVID-19 infection may exacerbate the MS disease and its relapses. Therefore, MS patients are more susceptible to infection because of their immunosuppressive or immunomodulatory medications. Objective We aimed to evaluate the knowledge, attitude, and behaviors of patients with MS in Saudi Arabia regarding the COVID-19 pandemic. Method A quantitative observational cross-sectional study was conducted. MS patients in Saudi Arabia were included in the study population. Data were collected via an online self-reported questionnaire from 214 participants from November 2020 to June 2021. Results A total of 214 MS patients participated in this study. The gender distribution showed that the male participants represented 38.3% (n = 82), while female participants accounted for 61.7% (n = 132).Most MS patients understood the COVID-19 preventive measures. The mean knowledge score was 15.7 (SD = 2.34, range: 1-20), showing an appropriate level of knowledge. While the mean behaviors score was 6.1 (SD = 1.2, range: 2-9), showing good behaviors. The mean score for attitude was 5.4 (SD = 1.77, range: 1-8), showing optimistic attitudes. However, a closer analysis of the participants' answers showed that 74.3% of the patients agreed that the treatment plan should be discussed with their doctors during the pandemic. In addition, almost half of the participants (49.1%) agreed that being an MS patient means they are at higher risk of getting infected by the virus. Data also showed that 17% of patients continued to attend social events involving many people. Also, 28.0% of the patients reported being in crowded places. Conclusion MS patients' risk of COVID-19 might be linked to their knowledge, attitude, and behaviors. Our results suggest that although MS patients have a high knowledge and good attitude and behaviors, it is still essential to have health education programs among MS patients to reduce the risk of SARS-CoV-2 infection and the impact of the COVID-19 pandemic on MS patients' care. Knowledge, attitude, and behaviors toward the COVID-19 pandemic can highlight the importance of education programs and translate the findings into action to minimize the disease risk.

A CASE OF COMBINED CENTRAL AND PERIPHERAL DEMYELINATION IN A PATIENT WITH PEDIATRIC MULTIPLE SCLEROSIS AFTER SARS-COV-2 VACCINATION

We present a case of combined central and peripheral demyelination in a patient with pediatric multiple sclerosis after the first dose of ChAdOx1-S (Chimpanzee Adenovirus Oxford 1) vaccination. The patient presented with ascending flaccid quadriparesis with respiratory failure that required mechanical ventilation. The lumbar puncture revealed albuminocytological dissociation, was negative for presence of JCV (John Cunningham Virus) in the CSF (Cerebrospinal Fluid) and ruled out other infections. A few days later he developed anisocoria and multiple new enlarging acute demyelinating lesions in the brain MRI (Magnetic Resonance Imaging). He was treated with intravenous immunoglobulin, corticosteroids and plasma exchange with gradual improvement. All other diseases were excluded via MR Spectroscopy, MR Angiography and serum and CSF laboratory investigations. Seven months later, the patient is under intense physiotherapy and is improving every day.

Immune-mediated diseases involving central and peripheral nervous systems.

In addition to combined central and peripheral demyelination, other immune diseases could involve both the central nervous system (CNS) and peripheral nervous system (PNS). To identify immune-mediated diseases responsible for symptomatic combined central/peripheral nervous system involvement (ICCPs), we conducted a multicentric retrospective study and assessed clinical, electrophysiological, and radiological features of patients fulfilling our ICCP criteria. Thirty patients (20 males) were included and followed during a median of 79.5months (interquartile range [IQR]=43-145). The median age at onset was 51.5 years (IQR=39-58). Patients were assigned to one of four groups: (i) monophasic disease with concomitant CNS/PNS involvement including anti-GQ1b syndrome (acute polyradiculoneuropathy + rhombencephalitis, n= 2), checkpoint inhibitor-related toxicities (acute polyradiculoneuropathy + encephalitis, n= 3), and anti-glial fibrillary acidic protein astrocytopathy (subacute polyradiculoneuropathy and meningoencephalomyelitis with linear gadolinium enhancements, n= 2); (ii) chronic course with concomitant CNS/PNS involvement including paraneoplastic syndromes (ganglionopathy/peripheral hyperexcitability + limbic encephalitis, n= 4); (iii) chronic course with sequential CNS/PNS involvement including POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome (polyradiculoneuropathy + strokes, n= 2), histiocytosis (polyradiculoneuropathy + lepto-/pachymeningitis, n= 1), and systemic vasculitis (multineuropathy +CNS vasculitis/pachymeningitis, n= 2); and (iv) chronic course with concomitant or sequential CNS/PNS involvement including combined central and peripheral demyelination (polyradiculoneuropathy +CNS demyelinating lesions, n= 10) and connective tissue diseases (ganglionopathy/radiculopathy/multineuropathy + limbic encephalitis/transverse myelitis/stroke, n= 4). We diagnosed nine ICCPs. The timing of central and peripheral manifestations and the disease course help determine the underlying immune disease. When antibody against neuroglial antigen is identified, CNS and PNS involvement is systematically concomitant, suggesting a common CNS/PNS antigen and a simultaneous disruption of blood-nerve and blood-brain barriers.

Assessing the Relationship Between Pitch Perception and Neural Health in Cochlear Implant Users.

Various neural health estimates have been shown to indicate the density of spiral ganglion neurons in animal and modeling studies of cochlear implants (CIs). However, when applied to human CI users, these neural health estimates based on psychophysical and electrophysiological measures are not consistently correlated with each other or with the speech recognition performance. This study investigated whether the neural health estimates have stronger correlations with the temporal and place pitch sensitivity than with the speech recognition performance. On five electrodes in 12 tested ears of eight adult CI users, polarity effect (PE), multipulse integration (MPI), and interphase gap (IPG) effect on the amplitude growth function (AGF) of electrically evoked compound action potential (ECAP) were measured to estimate neural health, while thresholds of amplitude modulation frequency ranking (AMFR) and virtual channel ranking (VCR) were measured to indicate temporal and place pitch sensitivity. AzBio sentence recognition in noise was measured using the clinical CI processor for each ear. The results showed significantly poorer AMFR and VCR thresholds on the basal electrodes than on the apical and middle electrodes. Across ears and electrodes, only the IPG offset effect on ECAP AGF had a nearly significant negative correlation with the VCR threshold after removing the outliers. No significant across-ear correlations were found between the mean neural health estimates, mean pitch-ranking thresholds, and AzBio sentence recognition score. This study suggests that the central axon demyelination reflected by the IPG offset effect may be important for the place pitch sensitivity of CI users and that the IPG offset effect may be used to predict the perceptual resolution of virtual channels for CI programming.

Combined central and peripheral demyelination: a case report

Overlapping central nervous system (CNS) and peripheral nervous system (PNS) demyelination is a rare clinical entity, more frequently seen in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and multiple sclerosis (MS). This case report showcases a patient with atypical CIDP and CNS demyelination lesions. Demographic data, disease course, treatment responsiveness, neurological examination, laboratory tests, nerve conduction studies (NCS), and brain and spinal cord MRI were registered. The case highlights the difficulty of diagnosis establishment and treatment selection, given the atypical course of the disease and limited answers to the indicated therapies. The data from our report suggest that specific and widely available immunological targets are necessary for diagnosing combined central and peripheral demyelination cases appropriately. The association of different immunotherapeutic agents may be necessary to induce and maintain disease remission.

Peripheral neuropathy and MOG-IgG: A clinical and neuropathological retrospective study

BackgroundMyelin oligodendrocyte glycoprotein antibodies (MOG-Abs) may rarely be associated with peripheral nervous system involvement. We aimed to test MOG-Abs in patients with undetermined peripheral neuropathy (PN). MethodsConsecutive patients with available sural nerve biopsy and paired serum sample were retrospectively identified (January, 1st 2016-November, 1st 2021) and tested for MOG-Abs with live cell-based assay (CBA). Patients with antibody titre ≥1:160 (secondary H + L antibody) and selective MOG-IgG presence (IgG-Fc predominance) were considered MOG-IgG positive. All positive samples were analysed with immunohistochemistry and CBAs for antibodies against Neurofascin-155 and Contactin-1. Clinical and neuropathological data were collected through clinical reports. ResultsAmong 163 patients, 5 (3%) resulted positive for predominantly IgG MOG-Abs (median titer 1:320, range 1:160–1:5120), none showed other concomitant antibodies. Median age was 74 years-old (range 55–81), median disease duration was 60 months (range 1–167), 60% of patients were female. Of these, 4/5 cases had clinical features suggestive of acute (n = 1) or chronic (n = 3) inflammatory demyelinating neuropathy, 2/5 fulfilled the criteria of combined central and peripheral demyelination (CCPD) whilst 3/5 had isolated PNS involvement. Neuropathological findings showed mixed axonal-demyelinating features in 2/5, predominant demyelination in 3/5 cases. Other neuropathological hallmarks included paranodal demyelination (n = 3), myelin outfoldings (n = 4), slight inflammatory infiltrates (n = 3), onion bulbs (n = 3), and clusters of regeneration (n = 4). DiscussionMOG-IgG can be detected in patients with isolated PN or CCPD. Clinical and neuropathological features are suggestive for demyelination and slight inflammation. Further studies should include larger cohorts of patients to elucidate the utility of MOG-Abs testing in PN.

Forskolin, an Adenylcyclase/cAMP/CREB Signaling Activator Restoring Myelin-Associated Oligodendrocyte Destruction in Experimental Ethidium Bromide Model of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic neurodegenerative disease marked by oligodendrocyte loss, which results in central neuronal demyelination. AC/cAMP/CREB signaling dysregulation is involved in the progression of MS, including mitochondrial dysfunctions, reduction in nerve growth factors, neuronal inflammation, apoptosis, and white matter degeneration. Our previous research has shown that Forskolin (FSK), a naturally occurring direct adenylyl cyclase (AC)/cAMP/CREB activator, has neuroprotective potential to alleviate pathogenic factors linked with numerous neurological abnormalities. The current study intends to explore the neuroprotective potential of FSK at doses of 40 mg/kg and 60 mg/kg alone, as well as in combination with conventional medicines, such as Fingolimod (FNG), Donepezil (DON), Memantine (MEM), and Simvastatin (SIM) in EB-induced demyelinated experimental MS rats. Adult Wistar rats were divided into nine groups, and EB was infused stereotaxically in the rat brain’s intracerebropeduncle (ICP) area. Chronic gliotoxin EB treatment results in demyelination as well as motor and cognitive dysfunctions. FSK, combined with standard medications, improves behavioral dysfunctions, such as neuromuscular and motor deficits and memory and cognitive abnormalities. Following pharmacological treatments improved remyelination by enhancing myelin basic protein and increasing AC, cAMP, and CREB levels in brain homogenates. Furthermore, FSK therapy restored brain mitochondrial-ETC complex enzymes and neurotransmitter levels while decreasing inflammatory cytokines and oxidative stress markers. The Luxol fast blue (LFB) stain results further indicate FSK’s neuroprotective potential in preventing oligodendrocyte death. Therefore, the results of these studies contribute to a better understanding of the possible role that natural phytochemicals FSK could have in preventing motor neuron diseases, such as multiple sclerosis.

TU-186. Combined central and peripheral demyelination in a patient presenting with Acute Severe Ascending Paralysis

TU-186. Combined central and peripheral demyelination in a patient presenting with Acute Severe Ascending Paralysis

A case study of combined central and peripheral demyelination with antibodies against paranodal protein neurofascin 186

We report the diagnostic process of a rare patient with a combined central and peripheral demyelinating disease with antibodies against paranodal protein neurofascin 186 (anti– NF186)—the patient presented with weakness in both lower limbs. The clinical process and evidence are similar to subacute combined degeneration. However, thoracic spinal MRI shows T1 equal signal, and T2 high signal lesions in thoracic vertebrae 5-7 mainly involve white matter. The Aquaporin 4 antibody of the central nervous system indicates the disease is of an optic neuromyelitis pedigree. The antibodies against paranodal protein neurofascin 186 indicate demyelinating peripheral nerve pathogenesis. The final diagnosis was a combined central and peripheral demyelinating disease based on the results of various examinations. The patient's condition improved after methylprednisolone therapy and intravenous immunoglobulin.

THE POTENTIAL ROLE OF EPSTEIN-BARR VIRUS NUCLEAR ANTIGEN-1 (EBNA-1) IN MULTIPLE SCLEROSIS

Background: Multiple sclerosis (MS) is a disease affecting the central nervous system (CNS), with inflammation and demyelination of nerves, eventually resulting in nerve damage and disabilities. The risk of developing MS enlarged by infectious mononucleosis, which is caused by delayed primary infection by Epstein-Barr Virus (EBV). Early reports consistently demonstrated an increased antibody response in MS patients versus healthy subjects towards different EBV antigens, including the EBV nuclear antigen-1 (EBNA-1). In Iraq, number of researchers found that the EBV have a possible role at some point in the course of the disease, others reported that the EBV pathogenesis have an important role in the triggering of MS disease. Objective: To compare the sero-prevalence of EBV nuclear antigen-1 antibody (EBNA-1 IgG) among the Iraqi MS patients and controls and find out whether there is a relation between disease severity and EBNA-1 IgG titer. Methods: This case-control study conducted on 120 MS patients aged between 13-42 years, and 120 apparently healthy age- and sex-matched volunteers as controls. Three ml of whole blood were collected from all MS patients and controls and put in gel tubes. The blood samples were centrifuged at 5000 RPM for 5 minutes to get serum from the gel tubes. Serum was preserved in (-20ºC), and then used for enzyme-linked immunosorbent assay (ELISA). The ELISA study was performed using ELISAs kits (Abnova /Taiwan) for EBNA-1 IgG antibodies measurement. Results: EBNA-1 IgG was positive in 51.7% (62/120) of MS patients and 39.2% (47/120) of controls, (P=0.035). The median of EBNA-1 IgG level of MS patients and controls were 81.08 U/ml, and 67.73 U/ml, respectively (P=0.043). And EBNA-1IgG was significantly higher in younger age groups. Patients with the first-line and second-line treatment showed no significant differences in EBNA-1 IgG levels, while the median level in patients without treatment (newly diagnosed) and those who were at early years of the disease was higher. Conclusion: EBNA-1 antibody could play a triggering role in MS because it is significantly higher in MS patients than in controls, especially at younger age groups, early stages of the disease and in female patients. Keywords: Multiple sclerosis, EBV, EBNA-1 IgG, ELISA Citation: Ali ZA, Al-Obaidi AB, Almashta SA. The potential role of Epstein-Barr Virus Nuclear Antigen-1 (EBNA-1) in multiple sclerosis. Iraqi JMS. 2022; 20(1): 3-10. doi: 10.22578/IJMS.20.1.2

Cell-based flow cytometry assay for simultaneous detection of multiple autoantibodies in a single serum sample

Accurate serologic evaluation of autoantibodies in patients with autoimmune diseases is critical. In the present study, we established a live cell-based assay for simultaneous detection of multiple autoantibodies in a single serum sample. Autoantibody seropositivity was determined by 3-color flow cytometry using live Chinese hamster ovary cells transiently expressing a target protein of interest fused to enhanced green fluorescent protein and labeled with Alexa Fluor 647 and Hoechst 33342. As a representative example, we applied the strategy for simultaneous detection of 2 recently established biomarkers for central nervous system autoimmune inflammatory demyelinating disorders, anti-aquaporin-4 autoantibody and anti-myelin oligodendrocyte glycoprotein autoantibody, in a single serum sample. This analysis revealed the coexistence of these 2 autoantibodies. We demonstrated that this assay can simultaneously detect 3 different autoantibodies. We propose a quadrant gating strategy of flow cytometry contour plots to clearly distinguish seropositive sera from seronegative sera regardless of the extent of the background signal level or the autoantibody titer. This novel and practical method using a combination of fluorescent proteins and fluorochromes to simultaneously detect multiple autoantibodies improves the efficiency of evaluating serum samples, and therefore provides significant benefits to both the patient and the healthcare professionals performing autoantibody testing.

Combined central and peripheral demyelination syndrome after COVID-19 vaccination with brisk response to plasma exchange and steroids (P18-1.003)

Combined central and peripheral demyelination syndrome after COVID-19 vaccination with brisk response to plasma exchange and steroids (P18-1.003)

Benefit of nerve ultrasound in patients with combined central and peripheral demyelination (CCPD) (P4-13.001)

Benefit of nerve ultrasound in patients with combined central and peripheral demyelination (CCPD) (P4-13.001)

Application of a triple‐helical peptide inhibitor of MMP‐2/MMP‐9 to examine T‐cell activation in experimental autoimmune encephalomyelitis

AbstractMultiple sclerosis (MS) is an inflammatory demyelinating disease whereby pathology includes multifocal perivascular mononuclear cell infiltration into the central nervous system, oligodendrocyte loss and demyelination, and variable axonal loss. Little is known about the causative agent in MS, but the matrix metalloproteinase (MMP) family of proteolytic enzymes has been implicated in disease progression and resolution. Recent studies revealed that MMP‐2 and/or MMP‐9 are required for an effective T‐cell‐mediated immune response to antigenic stimulation. In the present studies, we used an MMP‐2/MMP‐9 selective triple‐helical peptide inhibitor (THPI) to examine the role of these enzymes in antigen specific T‐cell responses. We found that treatment of murine CD4+ T‐cells with the THPI, followed by CD3/CD28 stimulation of the T‐cell receptor (TCR), resulted in reduced cell proliferation and production of interleukin 2 (IL‐2), interferon gamma (IFN‐γ), and tumor‐necrosis factor alpha (TNF‐α). Application of the THPI in experimental autoimmune encephalomyelitis (EAE), a widely accepted animal model of MS, reduced clinical severity of the disease and weight loss. Splenocytes isolated from THPI‐treated EAE animals had reduced proliferation compared with untreated animals. In an in vitro recall experiment, splenocytes isolated from EAE mice were treated with the THPI, followed by CD3/CD28 stimulation of the TCR. Treated splenocytes had reduced production of IL‐2, IL‐6, IL‐10, IFN‐γ, and TNF‐α compared with untreated splenocytes isolated from EAE mice. Overall, the MMP‐2/MMP‐9‐targeting THPI modulates T‐cell response to antigenic stimulation, including proliferation and immune cell production of specific cytokines, providing insight as to why the THPI is effective in reducing the clinical severity of EAE.