Monoclonal antibodies for the management of central nervous system diseases: clinical success and future strategies

Singh Gautam, Avtar; Pandey, Shivam Kumar; Lasure, Vaibhav; Dubey, Sachin; Singh, Rakesh Kumar

doi:10.1080/14712598.2023.2227378

Expert Opinion on Biological Therapy

2023

DOI: 10.1080/14712598.2023.2227378

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Monoclonal antibodies for the management of central nervous system diseases: clinical success and future strategies

Avtar Singh Gautam,

Shivam Kumar Pandey,

Vaibhav Lasure

et al.

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Cited by 6 publications

References 129 publications

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Recombinant Antibody Fragments for Immunotherapy of Parkinson’s Disease

Manoutcharian,

Gevorkian

2024

BioDrugs

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Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. Multiple genetic and environmental factors leading to progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SN) and consequent depletion of dopamine were described. Current clinical approaches, such as dopamine replacement or deep brain stimulation using surgically implanted probes, provide symptomatic relief but cannot modify disease progression. Therefore, disease-modifying therapeutic tools are urgently needed. Immunotherapy approaches, including passive transfer of protective antibodies and their fragments, have shown therapeutic efficacy in several animal models of neurodegenerative diseases, including PD. Recombinant antibody fragments are promising alternatives to conventional full-length antibodies. Modern computational approaches and molecular biology tools, directed evolution methodology, and the design of tissue-penetrating fusion peptides allowed for the development of recombinant antibody fragments with superior specificity and affinity, reduced immunogenicity, the capacity to target hidden epitopes and cross the blood-brain barrier (BBB), higher solubility and stability, the ability to refold after heat denaturation, and inexpensive large-scale production. In addition, antibody fragments do not induce microglia Fcγ receptor (FcγR)-mediated proinflammatory response and tissue damage in the central nervous system (CNS), because they lack the Fc portion of the immunoglobulin molecule. In the present review, we summarized data on recombinant antibody fragments evaluated as immunotherapeutics in preclinical models of PD and discussed their potential for developing therapeutic and preventive protocols for patients with PD.

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Recombinant Antibody Fragments for Immunotherapy of Parkinson’s Disease

Manoutcharian,

Gevorkian

2024

BioDrugs

View full text Add to dashboard Cite

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Exosome-mediated delivery platform of biomacromolecules into the brain: Cetuximab in combination with doxorubicin for glioblastoma therapy

Chu,

Sun,

Zhao

et al. 2024

International Journal of Pharmaceutics

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The Relevance and Implications of Monoclonal Antibody Therapies on Traumatic Brain Injury Pathologies

Wang,

Okada-Rising,

Scultetus

et al. 2024

Biomedicines

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Traumatic brain injury (TBI) is a global public health concern. It remains one of the leading causes of morbidity and mortality. TBI pathology involves complex secondary injury cascades that are associated with cellular and molecular dysfunction, including oxidative stress, coagulopathy, neuroinflammation, neurodegeneration, neurotoxicity, and blood–brain barrier (BBB) dysfunction, among others. These pathological processes manifest as a diverse array of clinical impairments. They serve as targets for potential therapeutic intervention not only in TBI but also in other diseases. Monoclonal antibodies (mAbs) have been used as key therapeutic agents targeting these mechanisms for the treatment of diverse diseases, including neurological diseases such as Alzheimer’s disease (AD). MAb therapies provide a tool to block disease pathways with target specificity that may be capable of mitigating the secondary injury cascades following TBI. This article reviews the pathophysiology of TBI and the molecular mechanisms of action of mAbs that target these shared pathological pathways in a wide range of diseases. Publicly available databases for various applications of mAb therapy were searched and further classified to assess relevance to TBI pathology and evaluate current stages of development. The authors intend for this review to highlight the potential impact of current mAb technology within pathological TBI processes.

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Monoclonal antibodies for the management of central nervous system diseases: clinical success and future strategies

Cited by 6 publications

References 129 publications

Recombinant Antibody Fragments for Immunotherapy of Parkinson’s Disease

Recombinant Antibody Fragments for Immunotherapy of Parkinson’s Disease

Exosome-mediated delivery platform of biomacromolecules into the brain: Cetuximab in combination with doxorubicin for glioblastoma therapy

The Relevance and Implications of Monoclonal Antibody Therapies on Traumatic Brain Injury Pathologies

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