Type-1 diabetes is the most common diabetes in children and autoimmune. These people are three-times more prone to develop MS than the general population.
Identification of common key genes and pathways between type 1 diabetes and multiple sclerosis using transcriptome and interactome analysis
https://link.springer.com/article/10.10 ... 19-02181-8
Purpose
Type 1 diabetes (T1D) and multiple sclerosis (MS) are classified as T cell-mediated autoimmune diseases. Although convergent evidence proposed common genetic architecture for autoimmune diseases, it remains a challenge to identify them. This study aimed to determine common gene signature and pathways in T1D and MS via systems biology approach.
Methods
Gene expression profiles of peripheral blood mononuclear cells (PBMCs) and pancreatic-β cells in T1D as well as PBMCs and cerebrospinal fluid (CSF) in MS were analyzed in our previous published data, and differential expressed genes were integrated with protein–protein interactions data to construct Query–Query PPI (QQPPI) networks. In this study, QQPPI networks were further analyzed to investigate more central genes, functional modules and complexes shared in T1D and MS progression. Lastly, the interaction of common genes with drugs was also explored.
Results
Several cytokines such as IL-23A, IL-32, IL-34, and IL-37 tend to be differentially expressed in both diseases. In addition, PSMA1, MYC, SRPK1, YBX1, HNRNPM, NF-κB2, IKBKE, RAC1, FN1, ARRB2, ESR1, HSP90AB1, and PPP1CA were common high central genes in QQPPI networks corresponding to each disease. Proteasome, spliceosome, immune responses, apoptosis, cellular communication/signaling transduction mechanism, interaction with environment, and activity of intercellular mediators were shared biological processes in T1D and MS. Finally, azathioprine, melatonin, resveratrol, and geldanamycin identified as prioritized drugs for the treatment of patients with T1D and MS.
Conclusions
This study represented novel key genes and pathways shared between T1D and MS, which may facilitate the identification of potential therapeutic targets in these diseases.
Relationship between MS and type-1 diabetes
Temelimab under study also for type-I diabetes
https://european-biotechnology.com/up-t ... rosis.html
The 12-months trial, which will kick-off in QI/2020, will be led by Dr. Fredrik Piehl, head of research at the MS clinic at ASC in Stockholm, which is home to approximately 2,400 patients. It will enroll patients whose disability progresses without relapses, and will document the safety and tolerability of temelimab following higher doses, as well as efficacy based on the latest biomarkers associated with disease progression.
Geneuro’s temelimab targets pHERV-W Env, the envelope protein of a Human Endogenous Retrovirus (HERV). Based on Phase IIb data, Geneuro believes its expression to be reactivated in order to trigger activation of microglia, the brain’s immune system resulting myelin destruction. Furthermore, the reactivated endogenous gene may impair the remyelination capacity of the brain through the inhibition of oligodendrocyte precursor cell differentiation.
The development of temelimab (GNbAC1) is the result of 25 years of research into human endogenous retroviruses (HERVs), before GeNeuro was founded in 2006. HERVs are present in the human genome and some have been associated with various auto-immune diseases.
The viral envelope protein encoded by a HERV in the HERV-W family (pHERV-W Env) has been found in MS patients and particularly in active lesions, as well as in the pancreas in type-1 diabetes patients. By neutralising pHERV-W Env, temelimab could simultaneously block the pathological inflammation process and restore the remyelination process in MS patients, and maintain insulin production in type-1 diabetes patients
The 12-months trial, which will kick-off in QI/2020, will be led by Dr. Fredrik Piehl, head of research at the MS clinic at ASC in Stockholm, which is home to approximately 2,400 patients. It will enroll patients whose disability progresses without relapses, and will document the safety and tolerability of temelimab following higher doses, as well as efficacy based on the latest biomarkers associated with disease progression.
Geneuro’s temelimab targets pHERV-W Env, the envelope protein of a Human Endogenous Retrovirus (HERV). Based on Phase IIb data, Geneuro believes its expression to be reactivated in order to trigger activation of microglia, the brain’s immune system resulting myelin destruction. Furthermore, the reactivated endogenous gene may impair the remyelination capacity of the brain through the inhibition of oligodendrocyte precursor cell differentiation.
The development of temelimab (GNbAC1) is the result of 25 years of research into human endogenous retroviruses (HERVs), before GeNeuro was founded in 2006. HERVs are present in the human genome and some have been associated with various auto-immune diseases.
The viral envelope protein encoded by a HERV in the HERV-W family (pHERV-W Env) has been found in MS patients and particularly in active lesions, as well as in the pancreas in type-1 diabetes patients. By neutralising pHERV-W Env, temelimab could simultaneously block the pathological inflammation process and restore the remyelination process in MS patients, and maintain insulin production in type-1 diabetes patients
More about MS and type-1 diabetes
Not always MS and type1 diabetes are related. But MS could be more than one disease, and maybe a subtype is related.
An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes.
Source: https://www.ncbi.nlm.nih.gov/pubmed/28878130
Abstract
Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies.
In particular, the envelope protein of HERV-W family (HERV-W-Env) has been involved in multiple sclerosis pathogenesis. Investigations to detect HERV-W-Env in a few other autoimmune diseases were negative, except in type-1 diabetes (T1D).
In patients suffering from T1D, HERV-W-Env protein was detected in 70% of sera, and its corresponding RNA was detected in 57% of peripheral blood mononuclear cells. While studies on human Langerhans islets evidenced the inhibition of insulin secretion by HERV-W-Env, this endogenous protein was found to be expressed by acinar cells in 75% of human T1D pancreata. An extensive immunohistological analysis further revealed a significant correlation between HERV-W-Env expression and macrophage infiltrates in the exocrine part of human pancreata.
Such findings were corroborated by in vivo studies on transgenic mice expressing HERV-W-env gene, which displayed hyperglycemia and decreased levels of insulin, along with immune cell infiltrates in their pancreas. Altogether, these results strongly suggest an involvement of HERV-W-Env in T1D pathogenesis. They also provide potentially novel therapeutic perspectives, since unveiling a pathogenic target in T1D.
An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes.
Source: https://www.ncbi.nlm.nih.gov/pubmed/28878130
Abstract
Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies.
In particular, the envelope protein of HERV-W family (HERV-W-Env) has been involved in multiple sclerosis pathogenesis. Investigations to detect HERV-W-Env in a few other autoimmune diseases were negative, except in type-1 diabetes (T1D).
In patients suffering from T1D, HERV-W-Env protein was detected in 70% of sera, and its corresponding RNA was detected in 57% of peripheral blood mononuclear cells. While studies on human Langerhans islets evidenced the inhibition of insulin secretion by HERV-W-Env, this endogenous protein was found to be expressed by acinar cells in 75% of human T1D pancreata. An extensive immunohistological analysis further revealed a significant correlation between HERV-W-Env expression and macrophage infiltrates in the exocrine part of human pancreata.
Such findings were corroborated by in vivo studies on transgenic mice expressing HERV-W-env gene, which displayed hyperglycemia and decreased levels of insulin, along with immune cell infiltrates in their pancreas. Altogether, these results strongly suggest an involvement of HERV-W-Env in T1D pathogenesis. They also provide potentially novel therapeutic perspectives, since unveiling a pathogenic target in T1D.
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