Temelimab

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Temelimab
Monoclonal antibody
Type ?
Legal status
Legal status
  • Experimental

Temelimab (also known as GNbAC1 [1] ) is an experimental monoclonal antibody drug for immune system conditions that neutralizes the human endogenous retrovirus envelope protein HERV-W. [2] [3] It has been studied for multiple sclerosis up to phase 2b, where it was found to be safe and to reduce brain lesions. [1] As of 2023, it is also being studied for cognitive impairment in long COVID. [4]

Related Research Articles

<span class="mw-page-title-main">Multiple sclerosis</span> Disease that damages the myelin sheaths around nerves

Multiplesclerosis (MS) is a autoimmune disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. Specific symptoms can include double vision, vision loss, eye pain, muscle weakness, and loss of sensation or coordination. MS takes several forms, with new symptoms either occurring in isolated attacks or building up over time. In the relapsing forms of MS, between attacks, symptoms may disappear completely, although some permanent neurological problems often remain, especially as the disease advances. In the progressive forms of MS, bodily function slowly deteriorates and disability worsens once symptoms manifest and will steadily continue to do so if the disease is left untreated.

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.

<span class="mw-page-title-main">Monoclonal antibody</span> Antibodies from clones of the same blood cell

A monoclonal antibody is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.

Daclizumab is a therapeutic humanized monoclonal antibody which was used for the treatment of adults with relapsing forms of multiple sclerosis (MS). Daclizumab works by binding to CD25, the alpha subunit of the IL-2 receptor of T-cells.

<span class="mw-page-title-main">Rituximab</span> Biopharmaceutical drug

Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein–Barr virus-positive mucocutaneous ulcers. It is given by slow intravenous infusion. Biosimilars of Rituxan include Blitzima, Riabni, Ritemvia, Rituenza, Rixathon, Ruxience, and Truxima.

Neuromyelitis optica spectrum disorders (NMOSD), including neuromyelitis optica (NMO), are autoimmune diseases characterized by acute inflammation of the optic nerve and the spinal cord (myelitis). Episodes of ON and myelitis can be simultaneous or successive. A relapsing disease course is common, especially in untreated patients. In more than 80% of cases, NMO is caused by immunoglobulin G autoantibodies to aquaporin 4 (anti-AQP4), the most abundant water channel protein in the central nervous system. A subset of anti-AQP4-negative cases is associated with antibodies against myelin oligodendrocyte glycoprotein (anti-MOG). Rarely, NMO may occur in the context of other autoimmune diseases or infectious diseases. In some cases, the etiology remains unknown.

<span class="mw-page-title-main">Endogenous retrovirus</span> Inherited retrovirus encoded in an organisms genome

Endogenous retroviruses (ERVs) are endogenous viral elements in the genome that closely resemble and can be derived from retroviruses. They are abundant in the genomes of jawed vertebrates, and they comprise up to 5–8% of the human genome.

<span class="mw-page-title-main">Cladribine</span> Pharmaceutical drug

Cladribine, sold under the brand name Leustatin, among others, is a medication used to treat hairy cell leukemia and B-cell chronic lymphocytic leukemia. Cladribine, sold under the brand name Mavenclad, is used for the treatment of adults with highly active forms of relapsing-remitting multiple sclerosis.

<span class="mw-page-title-main">Alemtuzumab</span> Medication used to treat chronic lymphocytic leukemia (CLL)

Alemtuzumab, sold under the brand names Campath and Lemtrada among others, is a medication used to treat chronic lymphocytic leukemia (CLL) and multiple sclerosis. In CLL, it has been used as both a first line and second line treatment. In MS it is generally only recommended if other treatments have not worked. It is given by injection into a vein.

Experimental autoimmune encephalomyelitis, sometimes experimental allergic encephalomyelitis (EAE), is an animal model of brain inflammation. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with rodents and is widely studied as an animal model of the human CNS demyelinating diseases, including multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). EAE is also the prototype for T-cell-mediated autoimmune disease in general.

A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment. The important side effects of TNF inhibitors include lymphomas, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.

Inflammatory demyelinating diseases (IDDs), sometimes called Idiopathic (IIDDs) due to the unknown etiology of some of them, are a heterogenous group of demyelinating diseases - conditions that cause damage to myelin, the protective sheath of nerve fibers - that occur against the background of an acute or chronic inflammatory process. IDDs share characteristics with and are often grouped together under Multiple Sclerosis. They are sometimes considered different diseases from Multiple Sclerosis, but considered by others to form a spectrum differing only in terms of chronicity, severity, and clinical course.

Ocrelizumab, sold under the brand name Ocrevus, is a medication used for the treatment of multiple sclerosis (MS). It is a humanized anti-CD20 monoclonal antibody. It targets CD20 marker on B lymphocytes and is an immunosuppressive drug. Ocrelizumab binds to an epitope that overlaps with the epitope to which rituximab binds.

Research in multiple sclerosis may find new pathways to interact with the disease, improve function, curtail attacks, or limit the progression of the underlying disease. Many treatments already in clinical trials involve drugs that are used in other diseases or medications that have not been designed specifically for multiple sclerosis. There are also trials involving the combination of drugs that are already in use for multiple sclerosis. Finally, there are also many basic investigations that try to understand better the disease and in the future may help to find new treatments.

<span class="mw-page-title-main">Syncytin-1</span> Protein-coding gene in the species Homo sapiens

Syncytin-1 also known as enverin is a protein found in humans and other primates that is encoded by the ERVW-1 gene. Syncytin-1 is a cell-cell fusion protein whose function is best characterized in placental development. The placenta in turn aids in embryo attachment to the uterus and establishment of a nutrient supply.

Siltuximab is a chimeric monoclonal antibody. It binds to interleukin-6. Siltuximab has been investigated for the treatment of neoplastic diseases: metastatic renal cell cancer, prostate cancer, other types of cancer, and for Castleman's disease.

Human endogenous retrovirus K (HERV-K) or Human teratocarcinoma-derived virus (HDTV) is a family of human endogenous retroviruses associated with malignant tumors of the testes. Phylogenetically, the HERV-K group belongs to the ERV2 or Class II or Betaretrovirus-like supergroup. Over the past several years, it has been found that this group of ERVs play an important role in embryogenesis, but their expression is silenced in most cell types in healthy adults. The HERV-K family, and particularly its subgroup HML-2, is the youngest and most transcriptionally active group and hence, it is the best studied among other ERVs. Reactivation of it or anomalous expression of HML-2 in adult tissues has been associated with various types of cancer and with neurodegenerative diseases such as amytrophic lateral sclerosis (ALS). Endogenous retrovirus K (HERV-K) is related to mammary tumor virus in mice. It exists in the human and cercopithecoid genomes. Human genome contains hundreds of copies of HERV-K and many of them possess complete open reading frames (ORFs) that are transcribed and translated, especially in early embryogenesis and in malignancies. One notable location of HERV-K is the C4 gene of RCCX module. HERV-K is also found in apes and Old World monkeys. It is uncertain how long ago in primate evolution the full-length HERV-K proviruses which are in the human genome today were created.

MOG antibody disease (MOGAD) or MOG antibody-associated encephalomyelitis (MOG-EM) is an inflammatory demyelinating disease of the central nervous system. Serum anti-myelin oligodendrocyte glycoprotein antibodies are present in up to half of patients with an acquired demyelinating syndrome and have been described in association with a range of phenotypic presentations, including acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, and neuromyelitis optica.

Human Endogenous Retrovirus-W (HERV-W) is a family of Human Endogenous Retroviruses, or HERVs.

There are several ways for pharmaceuticals for treating multiple sclerosis (MS) to reach the market.

References

  1. 1 2 Irfan SA, Murtaza M, Ahmed A, Altaf H, Ali AA, Shabbir N, Baig MM (May 2022). "Promising role of temelimab in multiple sclerosis treatment". Multiple Sclerosis and Related Disorders. 61: 103743. doi:10.1016/j.msard.2022.103743. PMID   35344907. S2CID   247489555.
  2. Mouliou DS, Dardiotis E (August 2022). "Temelimab for MS and SARS-CoV-2: Could it be a double-edged blessing?". Multiple Sclerosis and Related Disorders. 64: 103938. doi:10.1016/j.msard.2022.103938. PMC   9169463 . PMID   35717898.
  3. Kornmann G, Curtin F (December 2020). "Temelimab, an IgG4 Anti-Human Endogenous Retrovirus Monoclonal Antibody: An Early Development Safety Review". Drug Safety. 43 (12): 1287–1296. doi:10.1007/s40264-020-00988-3. PMID   32794123. S2CID   221126453.
  4. Bonilla H, Peluso MJ, Rodgers K, Aberg JA, Patterson TF, Tamburro R, et al. (2023-03-09). "Therapeutic trials for long COVID-19: A call to action from the interventions taskforce of the RECOVER initiative". Frontiers in Immunology. 14: 1129459. doi: 10.3389/fimmu.2023.1129459 . PMC   10034329 . PMID   36969241.