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The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system, thus protecting the brain from harmful or unwanted substances in the blood. The blood–brain barrier is formed by endothelial cells of the capillary wall, astrocyte end-feet ensheathing the capillary, and pericytes embedded in the capillary basement membrane. This system allows the passage of some small molecules by passive diffusion, as well as the selective and active transport of various nutrients, ions, organic anions, and macromolecules such as glucose and amino acids that are crucial to neural function.
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.
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.
Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult the relative preservation of neuronal integrity implies a reduction in the rate of neuronal loss over time, which can be expressed as a differential equation.
Alemtuzumab, sold under the brand names Campath and Lemtrada among others, is a medication used to treat chronic lymphocytic leukemia and multiple sclerosis. In chronic lymphocytic leukemia, it has been used as both a first line and second line treatment. It is given by injection into a vein.
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.
Hemojuvelin (HJV), also known as repulsive guidance molecule C (RGMc) or hemochromatosis type 2 protein (HFE2), is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosis in humans, a severe form of hemochromatosis. In humans, the hemojuvelin protein is encoded by the HFE2 gene. Hemojuvelin is a member of the repulsive guidance molecule family of proteins. Both RGMa and RGMb are found in the nervous system, while hemojuvelin is found in skeletal muscle and the liver.
Rovelizumab, also known as LeukArrest and Hu23F2G, is a humanized monoclonal antibody which was an experimental immunosuppressive drug. It was developed by Icos to treat patients with haemorrhagic shock.
Citicoline (INN), also known as cytidine diphosphate-choline (CDP-choline) or cytidine 5'-diphosphocholine is an intermediate in the generation of phosphatidylcholine from choline, a common biochemical process in cell membranes. Citicoline is naturally occurring in the cells of human and animal tissue, in particular the organs.
Profilin-1 is a protein that in humans is encoded by the PFN1 gene.
Reticulon 4, also known as Neurite outgrowth inhibitor or Nogo, is a protein that in humans is encoded by the RTN4 gene that has been identified as an inhibitor of neurite outgrowth specific to the central nervous system. During neural development Nogo is expressed mainly by neurons and provides an inhibitory signal for the migration and sprouting of CNS endothelial (tip) cells, thereby restricting blood vessel density.
Repulsive guidance molecule A (RGMa) is a bone morphogenetic protein (BMP) co-receptor of the repulsive guidance molecule family. Together with BMPR1A and BMPR1B, as well as ACVR2A and BMPR2, it binds BMPs thereby activating the intracellular SMAD1/5/8 signalling pathway. In humans this protein is encoded by the RGMA gene.
Pridopidine is an orally administrated small molecule investigational drug. Pridopidine is a selective and potent Sigma-1 Receptor agonist. It is being developed by Prilenia Therapeutics and is currently in late-stage clinical development for Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS).
A trifunctional antibody is a monoclonal antibody with binding sites for two different antigens, typically CD3 and a tumor antigen, making it a type of bispecific monoclonal antibody. In addition, its intact Fc-part can bind to an Fc receptor on accessory cells like conventional monospecific antibodies. The net effect is that this type of drug links T cells and monocytes/macrophages, natural killer cells, dendritic cells or other Fc receptor expressing cells to the tumor cells, leading to their destruction.
TOL101, is a murine-monoclonal antibody specific for the human αβ T cell receptor. In 2010 it was an Investigational New Drug under development by Tolera Therapeutics, Inc.
Ozanezumab is a monoclonal antibody designed for the treatment of ALS and multiple sclerosis.
Rapastinel is a novel antidepressant that was under development by Allergan as an adjunctive therapy for the treatment of treatment-resistant depression. It is a centrally active, intravenously administered amidated tetrapeptide that acts as a novel and selective modulator of the NMDA receptor. The drug is a rapid-acting and long-lasting antidepressant as well as robust cognitive enhancer by virtue of its ability to enhance NMDA receptor-mediated signal transduction and synaptic plasticity.
Tropoflavin, also known as 7,8-dihydroxyflavone, is a naturally occurring flavone found in Godmania aesculifolia, Tridax procumbens, and primula tree leaves. It has been found to act as a potent and selective small-molecule agonist of the tropomyosin receptor kinase B (TrkB), the main signaling receptor of the neurotrophin brain-derived neurotrophic factor (BDNF). Tropoflavin is both orally bioavailable and able to penetrate the blood–brain barrier. A prodrug of tropoflavin with greatly improved potency and pharmacokinetics, R13, is under development for the treatment of Alzheimer's disease.
A cerebroprotectant is a drug that is intended to protect the brain after the onset of acute ischemic stroke. As stroke is the second largest cause of death worldwide and a leading cause of adult disability, over 150 drugs have been tested in clinical trials to provide cerebroprotection.
Etrinabdione (VCE-004.8, EHP-101) is a drug structurally related to cannabidiol and HU-331 which has potent antiinflammatory and neuroprotective effects. It acts as a dual agonist of CB2 and PPARγ and is in clinical trials for the treatment of scleroderma.
References
- ↑ Huang, Lili; Fung, Emma; Bose, Sahana; Popp, Andreas; Böser, Preethne; Memmott, John; Kutskova, Yuliya A.; Miller, Renee; Tarcsa, Edit; Klein, Corinna; Veldman, Geertruida M.; Mueller, Bernhard K.; Cui, Yi-Fang (November 2021). "Elezanumab, a clinical stage human monoclonal antibody that selectively targets repulsive guidance molecule A to promote neuroregeneration and neuroprotection in neuronal injury and demyelination models". Neurobiology of Disease. 159: 105492. doi: 10.1016/j.nbd.2021.105492 . PMID 34478849. S2CID 237396110.
- ↑ Kalluri, Hari V.; Rosebraugh, Matthew R.; Misko, Thomas P.; Ziemann, Adam; Liu, Wei; Cree, Bruce A. C. (February 2023). "Phase 1 Evaluation of Elezanumab (Anti–Repulsive Guidance Molecule A Monoclonal Antibody) in Healthy and Multiple Sclerosis Participants". Annals of Neurology. 93 (2): 285–296. doi:10.1002/ana.26503. ISSN 0364-5134. PMC 10100020 . PMID 36093738.
- ↑ Jacobson, Peer B.; Goody, Robin; Lawrence, Matthew; Mueller, Bernhard K.; Zhang, Xiaomeng; Hooker, Bradley A.; Pfleeger, Kimberly; Ziemann, Adam; Locke, Charles; Barraud, Quentin; Droescher, Mathias; Bernhard, Joerg; Popp, Andreas; Boeser, Preethne; Huang, Lili; Mollon, Jennifer; Mordashova, Yulia; Cui, Yi-Fang; Savaryn, John P.; Grinnell, Christine; Dreher, Ingeborg; Gold, Michael; Courtine, Grégoire; Mothe, Andrea; Tator, Charles H.; Guest, James D. (July 2021). "Elezanumab, a human anti-RGMa monoclonal antibody, promotes neuroprotection, neuroplasticity, and neurorecovery following a thoracic hemicompression spinal cord injury in non-human primates". Neurobiology of Disease. 155: 105385. doi: 10.1016/j.nbd.2021.105385 . PMID 33991647. S2CID 234683099.
- ↑ Smith, Elaine; Ford, Andria L; Perez-Sanchez, Soledad; Shuaib, Ashfaq; Schwefel, Brittany; Ziemann, Adam (February 2022). "Abstract TP7: Phase 2a Study Of Elezanumab In Patients With Acute Ischemic Stroke". Stroke. 53 (Suppl_1). doi:10.1161/str.53.suppl_1.TP7. ISSN 0039-2499. S2CID 246602705.
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