RESUMEN
Addressing inflammation, demyelination, and associated neurodegeneration in inflammatory demyelinating diseases like multiple sclerosis (MS) remains challenging. ACT-1004-1239, a first-in-class and potent ACKR3 antagonist, currently undergoing clinical development, showed promise in preclinical MS models, reducing neuroinflammation and demyelination. However, its effectiveness in treating established disease and impact on remyelination after the occurrence of demyelinated lesions remain unexplored. This study assessed the therapeutic effect of ACT-1004-1239 in two demyelinating disease models. In the proteolipid protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE) model, ACT-1004-1239 administered upon the detection of the first signs of paralysis, resulted in a dose-dependent reduction in EAE disease severity, concomitant with diminished immune cell infiltrates in the CNS and reduced demyelination. Notably, efficacy correlated with elevated plasma concentrations of CXCL11 and CXCL12, two pharmacodynamic biomarkers of ACKR3 antagonism. Combining ACT-1004-1239 with siponimod, an approved immunomodulatory treatment for MS, synergistically reduced EAE severity. In the cuprizone-induced demyelination model, ACT-1004-1239 administered after 5 weeks of cuprizone exposure, significantly accelerated remyelination, already quantifiable one week after cuprizone withdrawal. Additionally, ACT-1004-1239 penetrated the CNS, elevating brain CXCL12 concentrations. These results demonstrate that ACKR3 antagonism significantly reduces the severity of experimental demyelinating diseases, even when treatment is initiated therapeutically, after the occurrence of lesions. It confirms the dual mode of action of ACT-1004-1239, exhibiting both immunomodulatory effects by reducing neuroinflammation and promyelinating effects by accelerating myelin repair. The results further strengthen the rationale for evaluating ACT-1004-1239 in clinical trials for patients with demyelinating diseases.
Asunto(s)
Encefalomielitis Autoinmune Experimental , Ratones Endogámicos C57BL , Remielinización , Animales , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Remielinización/efectos de los fármacos , Ratones , Femenino , Enfermedades Desmielinizantes/tratamiento farmacológico , Enfermedades Desmielinizantes/inducido químicamente , Cuprizona , Azetidinas/farmacología , Azetidinas/uso terapéutico , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/uso terapéutico , Compuestos de Bencilo/uso terapéutico , Compuestos de Bencilo/farmacología , Vaina de Mielina/efectos de los fármacos , Vaina de Mielina/metabolismoRESUMEN
The European Society of Toxicologic Pathology (ESTP) initiated a survey through its Pathology 2.0 workstream in partnership with sister professional societies in Europe and North America to generate a snapshot of artificial intelligence (AI) usage in the field of toxicologic pathology. In addition to demographic information, some general questions explored AI relative to (1) the current status of adoption across organizations; (2) technical and methodological aspects; (3) perceived business value and finally; and (4) roadblocks and perspectives. AI has become increasingly established in toxicologic pathology with most pathologists being supportive of its development despite some areas of uncertainty. A salient feature consisted of the variability of AI awareness and adoption among the responders, as the spectrum extended from pathologists having developed familiarity and technical skills in AI, to colleagues who had no interest in AI as a tool in toxicologic pathology. Despite a general enthusiasm for these techniques, the overall understanding and trust in AI algorithms as well as their added value in toxicologic pathology were generally low, suggesting room for the need for increased awareness and education. This survey will serve as a basis to evaluate the evolution of AI penetration and acceptance in this domain.
Asunto(s)
Inteligencia Artificial , Patólogos , Humanos , Algoritmos , Europa (Continente)RESUMEN
In situ hybridization (ISH) is used for the localization of specific nucleic acid sequences in cells or tissues by complementary binding of a nucleotide probe to a specific target nucleic acid sequence. In the last years, the specificity and sensitivity of ISH assays were improved by innovative techniques like synthetic nucleic acids and tandem oligonucleotide probes combined with signal amplification methods like branched DNA, hybridization chain reaction and tyramide signal amplification. These improvements increased the application spectrum for ISH on formalin-fixed paraffin-embedded tissues. ISH is a powerful tool to investigate DNA, mRNA transcripts, regulatory noncoding RNA, and therapeutic oligonucleotides. ISH can be used to obtain spatial information of a cell type, subcellular localization, or expression levels of targets. Since immunohistochemistry and ISH share similar workflows, their combination can address simultaneous transcriptomics and proteomics questions. The goal of this review paper is to revisit the current state of the scientific approaches in ISH and its application in drug research and development.
Asunto(s)
Patología Molecular , Opinión Pública , Adhesión en Parafina , Hibridación in Situ , ARN Mensajero/metabolismo , ADNRESUMEN
Current strategies for the treatment of demyelinating diseases such as multiple sclerosis (MS) are based on anti-inflammatory or immunomodulatory drugs. Those drugs have the potential to reduce the frequency of new lesions but do not directly promote remyelination in the damaged central nervous system (CNS). Targeting CXCR7 (ACKR3) has been postulated as a potential therapeutic approach in demyelinating diseases, leading to both immunomodulation by reducing leukocyte infiltrates and promyelination by enhancing myelin repair. ACT-1004-1239 is a potent, selective, insurmountable, and orally available first-in-class CXCR7 receptor antagonist. The effect of ACT-1004-1239 was evaluated in the myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) and the cuprizone-induced demyelination mouse models. In addition, ACT-1004-1239 was assessed in a rat oligodendrocyte precursor cell (OPC) differentiation assay in vitro. In the MOG-induced EAE model, ACT-1004-1239 treatment (10-100 mg/kg, twice daily, orally) showed a significant dose-dependent reduction in disease clinical scores, resulting in increased survival. At the highest dose tested (100 mg/kg, twice daily), ACT-1004-1239 delayed disease onset and significantly reduced immune cell infiltrates into the CNS and plasma neurofilament light chain concentration. Treatment with ACT-1004-1239 dose-dependently increased plasma CXCL12 concentration, which correlated with a reduction of the cumulative disease score. Furthermore, in the cuprizone model, ACT-1004-1239 treatment significantly increased the number of mature myelinating oligodendrocytes and enhanced myelination in vivo. In vitro, ACT-1004-1239 promoted the maturation of OPCs into myelinating oligodendrocytes. These results provide evidence that ACT-1004-1239 both reduces neuroinflammation and enhances myelin repair substantiating the rationale to explore its therapeutic potential in a clinical setting.
Asunto(s)
Cuprizona/farmacología , Inmunomodulación/efectos de los fármacos , Vaina de Mielina/efectos de los fármacos , Receptores CXCR/antagonistas & inhibidores , Animales , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/inmunología , Femenino , Inmunomodulación/inmunología , Inflamación/tratamiento farmacológico , Masculino , Ratones Endogámicos C57BL , Esclerosis Múltiple/tratamiento farmacológico , Vaina de Mielina/patología , Glicoproteína Mielina-Oligodendrócito/metabolismo , Oligodendroglía/citología , Oligodendroglía/efectos de los fármacos , Células Madre/citologíaRESUMEN
We describe Orbit Image Analysis, an open-source whole slide image analysis tool. The tool consists of a generic tile-processing engine which allows the execution of various image analysis algorithms provided by either Orbit itself or from other open-source platforms using a tile-based map-reduce execution framework. Orbit Image Analysis is capable of sophisticated whole slide imaging analyses due to several key features. First, Orbit has machine-learning capabilities. This deep learning segmentation can be integrated with complex object detection for analysis of intricate tissues. In addition, Orbit can run locally as standalone or connect to the open-source image server OMERO. Another important characteristic is its scale-out functionality, using the Apache Spark framework for distributed computing. In this paper, we describe the use of Orbit in three different real-world applications: quantification of idiopathic lung fibrosis, nerve fibre density quantification, and glomeruli detection in the kidney.
Asunto(s)
Órbita/anatomía & histología , Algoritmos , Aprendizaje Profundo , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Interfaz Usuario-ComputadorRESUMEN
The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions) Project (www.toxpath.org/inhand.asp) is a joint initiative of the societies of toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying lesions observed in most tissues and organs from the dog used in nonclinical safety studies. Some of the lesions are illustrated by color photomicrographs. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous lesions, lesions induced by exposure to test materials, and relevant infectious and parasitic lesions. A widely accepted and utilized international harmonization of nomenclature for lesions in laboratory animals will provide a common language among regulatory and scientific research organizations in different countries and increase and enrich international exchanges of information among toxicologists and pathologists.
Asunto(s)
Animales de Laboratorio , Animales , Bases de Datos Factuales , Perros , Europa (Continente) , JapónRESUMEN
The endothelin (ET) system has emerged as a novel target for hypertension treatment where a medical need persists despite availability of several pharmacological classes, including renin angiotensin system (RAS) blockers. ET receptor antagonism has demonstrated efficacy in preclinical models of hypertension, especially under low-renin conditions and in hypertensive patients. We investigated the pharmacology of aprocitentan (N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-sulfamide), a potent dual ETA/ETB receptor antagonist, on blood pressure (BP) in two models of experimental hypertension: deoxycorticosterone acetate (DOCA)-salt rats (low-renin model) and spontaneously hypertensive rats [(SHR), normal renin model]. We also compared the effect of its combination with RAS blockers (valsartan and enalapril) with that of the combination of the mineraloreceptor antagonist spironolactone with the same RAS blockers on BP and renal function in hypertensive rats. Aprocitentan was more potent and efficacious in lowering BP in conscious DOCA-salt rats than in SHRs. In DOCA-salt rats, single oral doses of aprocitentan induced a dose-dependent and long-lasting BP decrease and 4-week administration of aprocitentan dose dependently decreased BP (statistically significant) and renal vascular resistance, and reduced left ventricle hypertrophy (nonsignificant). Aprocitentan was synergistic with valsartan and enalapril in decreasing BP in DOCA-salt rats and SHRs while spironolactone demonstrated additive effects with these RAS blockers. In hypertensive rats under sodium restriction and enalapril, addition of aprocitentan further decreased BP without causing renal impairment, in contrast to spironolactone. In conclusion, ETA/ETB receptor antagonism represents a promising therapeutic approach to hypertension, especially with low-renin characteristics, and could be used in combination with RAS blockers, without increasing the risk of renal impairment.
Asunto(s)
Antihipertensivos/administración & dosificación , Antagonistas de los Receptores de Endotelina/administración & dosificación , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Pirimidinas/administración & dosificación , Sistema Renina-Angiotensina/efectos de los fármacos , Sulfonamidas/administración & dosificación , Animales , Antihipertensivos/farmacología , Acetato de Desoxicorticosterona/toxicidad , Quimioterapia Combinada , Antagonistas de los Receptores de Endotelina/farmacología , Hipertensión/inducido químicamente , Masculino , Pirimidinas/farmacología , Ratas , Ratas Endogámicas SHR , Ratas Wistar , Sistema Renina-Angiotensina/fisiología , Sulfonamidas/farmacologíaRESUMEN
AIMS: We compared the efficacy of macitentan, a novel dual endothelin A/endothelin B receptor antagonist, with that of another dual endothelin receptor antagonist, bosentan, in a rat model of non-vasoreactive pulmonary hypertension (PH) with particular emphasis on right ventricular (RV) remodeling. METHODS AND RESULTS: Unlike monocrotaline or hypoxic/sugen rats, bleomycin-treated rats presented a non-vasoreactive PH characterized by the absence of pulmonary dilatation to adenosine. We therefore chose the bleomycin rat model to compare the effects of the maximally effective doses of macitentan and bosentan on pulmonary vascular and RV remodeling. Macitentan (100 mg·kg(-1)·d(-1)), but not bosentan (300 mg·kg(-1)·d(-1)), significantly prevented pulmonary vascular remodeling, RV hypertrophy, and cardiomyocyte diameter increase. Cardiac protection by macitentan was associated with a significant attenuation of genes related to cell hypertrophy and extracellular matrix remodeling. Microautoradiography and high performance liquid chromatography analysis showed greater distribution of macitentan than bosentan in the RV and pulmonary tissue. CONCLUSIONS: Macitentan was more efficacious than bosentan in preventing the development of pulmonary and RV hypertrophies in a model of non-vasoreactive PH. Greater ability to distribute into the tissue could contribute to the greater structural improvement by macitentan compared with bosentan.
Asunto(s)
Antagonistas de los Receptores de Endotelina/farmacología , Ventrículos Cardíacos/efectos de los fármacos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertrofia Ventricular Derecha/prevención & control , Pirimidinas/farmacología , Sulfonamidas/farmacología , Función Ventricular Derecha/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Bleomicina , Bosentán , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/fisiopatología , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/fisiopatología , Hipertrofia Ventricular Derecha/inducido químicamente , Hipertrofia Ventricular Derecha/genética , Hipertrofia Ventricular Derecha/metabolismo , Hipertrofia Ventricular Derecha/fisiopatología , Masculino , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Arteria Pulmonar/fisiopatología , Ratas Wistar , Factores de Tiempo , Remodelación Vascular/efectos de los fármacosRESUMEN
The Göttingen minipig is one of the nonrodent species recommended by various regulatory authorities for safety assessment of drugs in preclinical studies. In such studies, knowledge of background pathology is critical in order to evaluate the potential renal toxicity. In the present study, the authors report 4 cases of glomerulonephritis out of 154 microbiologically defined Göttingen minipigs microscopically evaluated in preclinical studies. One animal required early sacrifice because of general poor health, and an additional animal died spontaneously. Histopathological evaluation revealed renal lesions in all 4 animals, exhibiting membranous or membranoproliferative glomerulonephritis at different stages, accompanied by secondary tubulo-interstitial damage. The renal changes observed were considered spontaneous in origin and of unknown etiology. Development of this condition in this strain should be considered in future studies.
Asunto(s)
Glomerulonefritis/veterinaria , Enfermedades de los Porcinos/patología , Fosfatasa Alcalina/sangre , Animales , Astenia/patología , Proliferación Celular , Femenino , Glomerulonefritis/patología , Hematuria/patología , Riñón/patología , Recuento de Leucocitos , Masculino , Modelos Animales , Porcinos , Porcinos Enanos , Pruebas de Toxicidad/métodos , Xenobióticos/toxicidadRESUMEN
BACKGROUND: Sjögren's syndrome is a systemic autoimmune disease characterized by immune cells predominantly infiltrating the exocrine glands and frequently forming ectopic lymphoid structures. These structures drive a local functional immune response culminating in autoantibody production and tissue damage, associated with severe dryness of mucosal surfaces and salivary gland hypofunction. Cenerimod, a potent, selective and orally active sphingosine-1-phosphate receptor 1 modulator, inhibits the egress of lymphocytes into the circulation. Based on the mechanism of action of cenerimod, its efficacy was evaluated in two mouse models of Sjögren's syndrome. METHODS: Cenerimod was administered in two established models of Sjögren's syndrome; firstly, in an inducible acute viral sialadenitis model in C57BL/6 mice, and, secondly, in the spontaneous chronic sialadenitis MRL/lpr mouse model. The effects of cenerimod treatment were then evaluated by flow cytometry, immunohistochemistry, histopathology and immunoassays. Comparisons between groups were made using a Mann-Whitney test. RESULTS: In the viral sialadenitis model, cenerimod treatment reduced salivary gland immune infiltrates, leading to the disaggregation of ectopic lymphoid structures, reduced salivary gland inflammation and preserved organ function. In the MRL/lpr mouse model, cenerimod treatment decreased salivary gland inflammation and reduced T cells and proliferating plasma cells within salivary gland ectopic lymphoid structures, resulting in diminished disease-relevant autoantibodies within the salivary glands. CONCLUSIONS: Taken together, these results suggest that cenerimod can reduce the overall autoimmune response and improve clinical parameters in the salivary glands in models of Sjögren's syndrome and consequently may reduce histological and clinical parameters associated with the disease in patients.
Asunto(s)
Sialadenitis , Síndrome de Sjögren , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos MRL lpr , Oxadiazoles , Glicoles de Propileno , Sialadenitis/tratamiento farmacológico , Síndrome de Sjögren/tratamiento farmacológicoRESUMEN
We examined whether high incidence rates (18%-56%) of inflammation in the root of the aorta detected in a Balb/c mouse model for hind limb ischemia were related to the surgical procedure. Twenty mice underwent ligation of the femoral artery; incidences of aortic root inflammation were compared to those observed in controls. We used a multiple-section sampling method to increase the sensitivity of the diagnostic rates. Although a cumulative incidence of 12.5% was found, no difference was seen in the overall incidence rates between the control and the surgically treated groups. Evaluation of blood levels of inflammatory cytokines showed that ligation of the femoral artery produced higher levels of interleukin-6 in the surgically transected group of mice. The development of spontaneous arteritis in this strain must be considered in future studies.
Asunto(s)
Aortitis/patología , Citocinas/sangre , Isquemia/patología , Animales , Aorta/patología , Aortitis/sangre , Aortitis/metabolismo , Modelos Animales de Enfermedad , Arteria Femoral/cirugía , Miembro Posterior/irrigación sanguínea , Histocitoquímica , Isquemia/sangre , Isquemia/etiología , Isquemia/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
In this study, 30 feline intestinal T-cell lymphomas (ITCLs) from 77 cats with gastrointestinal lymphoma were evaluated. Neoplastic lesions were composed predominantly of small (n = 21) or medium to large (n = 9) anaplastic cells. Different patterns of tumor growth were observed. A starry-sky pattern was evident in 7 cases (23.3%), fibrosis in 18 cases (60%), and neovascularization in 19 cases (63.3%). The cell proliferation index (assessed by MIB1 [mindbomb homolog 1] immunohistochemistry) ranged from 0.21% to 66.91%. Mean MIB1 index was 3.49% within the first 33rd percentile, 18.31% within the second 33rd percentile, and 40.16% within the third 33rd percentile (P < 0.000001). Microscopic and kinetic features provided evidence that ITCL in cats exhibits a spectrum in cytological composition and growth patterns that could putatively reflect differences in biologic behavior.
Asunto(s)
Enfermedades de los Gatos/patología , Neoplasias Intestinales/veterinaria , Linfoma de Células T/veterinaria , Animales , Gatos , Femenino , Inmunohistoquímica/veterinaria , Neoplasias Intestinales/patología , Linfoma de Células T/patología , Masculino , Estudios RetrospectivosRESUMEN
Intratracheal administration of bleomycin induces fibrosis in the lung, which is mainly assessed by histopathological grading that is subjective. Current literature highlights the need of reproducible and quantitative pulmonary fibrosis analysis. If some quantitative studies looked at fibrosis parameters separately, none of them quantitatively assessed both aspects: lung tissue remodeling and collagenization. To ensure reliable quantification, support vector machine learning was used on digitalized images to design a fully automated method that analyzes two important aspects of lung fibrosis: (i) areas having substantial tissue remodeling with appearance of dense fibrotic masses and (ii) collagen deposition. Fibrotic masses were identified on low magnification images and collagen detection was performed at high magnification. To insure a fully automated application the tissue classifier was trained on several independent studies that were performed over a period of four years. The detection method generates two different values that can be used to quantify lung fibrosis development: (i) percent area of fibrotic masses and (ii) percent of alveolar collagen. These two parameters were validated using independent studies from bleomycin- and saline-treated animals. A significant change of these lung fibrosis quantification parameters- increased amount of fibrotic masses and increased collagen deposition- were observed upon intratracheal administration of bleomycin and subsequent significant beneficial treatments effects were observed with BIBF-1120 and pirfenidone.
Asunto(s)
Bleomicina/administración & dosificación , Colágeno/metabolismo , Procesamiento de Imagen Asistido por Computador/métodos , Alveolos Pulmonares , Fibrosis Pulmonar , Animales , Bleomicina/farmacología , Modelos Animales de Enfermedad , Masculino , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/patología , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND AND HYPOTHESIS: We retrospectively evaluated the clinicopathologic findings and outcome predictors in dogs with Leptospira interrogans Australis serogroup infections. ANIMALS AND METHODS: The medical records of 159 dogs that had a leptospiral microscopic agglutination test (MAT) performed between 2001 and 2004 were reviewed. RESULTS: Twenty dogs met serologic criteria for either symptomatic (16 dogs) or asymptomatic (4 dogs) infection caused by Leptospira interrogans Australis serogroup. Seven of 16 symptomatic dogs died or were euthanized and 9/16 recovered. Systemic inflammatory response syndrome (SIRS) was observed in 9/16 dogs. The presence of SIRS did not affect prognosis (P = .357). C-reactive protein (CRP) and haptoglobin (Hpt) concentrations were altered in all symptomatic dogs, but results did not differ significantly between survivors and nonsurvivors (P = .08 and P = .055, respectively). Conversely, the CRP to Hpt ratio (CRP/Hpt) was significantly increased in nonsurvivors. Disseminated intravascular coagulation (DIC) was diagnosed in 7/16 dogs. DIC did not significantly affect outcome (P = .126). Multiple organ involvement was present with renal failure in 16/16, liver damage in 12/16, cardiac damage in 11/16, and muscular damage in 8/16 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Among the evaluated clinicopathologic biomarkers, serum albumin, cardiac troponin I, CRP/Hpt, urinary albumin, and urinary total protein to creatinine ratio were found to predict outcome and warrant evaluation in larger prospective studies.
Asunto(s)
Enfermedades de los Perros/microbiología , Leptospira interrogans serovar australis/aislamiento & purificación , Leptospirosis/veterinaria , Animales , Antibacterianos/uso terapéutico , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Femenino , Leptospirosis/tratamiento farmacológico , Leptospirosis/microbiología , Masculino , Estudios RetrospectivosRESUMEN
Sphingosine-1-phosphate receptor 1 (S1P1 ) modulators sequester circulating lymphocytes within lymph nodes, thereby preventing potentially pathogenic autoimmune cells from exiting into the blood stream and reaching inflamed tissues. S1P1 receptor modulation may thus offer potential to treat various autoimmune diseases. The first nonselective S1P1-5 receptor modulator FTY720/fingolimod/Gilenya® has successfully demonstrated clinical efficacy in relapsing forms of multiple sclerosis. However, cardiovascular, hepatic, and respiratory side-effects were reported and there is a need for novel S1P1 receptor modulators with better safety profiles. Here, we describe the discovery of cenerimod, a novel, potent and selective S1P1 receptor modulator with unique S1P1 receptor signaling properties and absence of broncho- and vasoconstrictor effects ex vivo and in vivo. Cenerimod dose-dependently lowered circulating lymphocyte counts in rats and mice after oral administration and effectively attenuated disease parameters in a mouse experimental autoimmune encephalitis (EAE) model. Cenerimod has potential as novel therapy with improved safety profile for autoimmune diseases with high unmet medical need.