New Strategies in Gene and Cell Therapy for Neurological Disorders

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 794

Special Issue Editor


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Guest Editor
Faculty of Nursing and Health Sciences, Nord University, Bodø, Norway
Interests: cancer; glioblastoma; gene therapy; cell therapy; immunotherapy; lentiviral vectors

Special Issue Information

Dear Colleagues,

Neurological disorders encompass a diverse spectrum of conditions affecting the central and peripheral nervous systems, including neurodegenerative diseases, neurodevelopmental disorders, neuropsychiatric conditions, genetic and metabolic disorders, CNS tumors, and trauma-induced injuries. Gene and cell therapy holds immense promise for treating these disorders, offering potential solutions for previously intractable conditions. Recent advancements in gene editing technologies, vector systems, cell-based regenerative medicine, immunomodulatory therapies, and delivery strategies have opened up new avenues for therapeutic interventions.

This Special Issue aims to feature cutting-edge gene and cell therapy research across the broad landscape of neurological disorders. Special attention will be paid to emerging technologies, including, but not limited to, nanotechnology, novel vectors, innovative delivery strategies to overcome the blood–brain barrier, and immunomodulatory interventions. Furthermore, reports on clinical trials or regulatory aspects will also be paid similar attention. This Special Issue welcomes the submission of original research articles demonstrating novel approaches, comprehensive reviews synthesizing current knowledge, and perspective pieces discussing future directions.

By bringing together diverse expertise in gene and cell therapy, neuroscience, and clinical translation, this Special Issue aims to accelerate the development of more effective treatments for neurological disorders.

We are pleased to invite you to submit original research articles, reviews, and case studies that address the aforementioned topics. Submissions should provide new insights, present innovative methodologies, or offer comprehensive reviews of current knowledge.

This Special Issue aims to place a spotlight on both breakthrough advances and critical challenges in gene and cell therapy for neurological disorders, encompassing neurodevelopmental, neurodegenerative, and neuropsychiatric disorders, CNS tumors, CNS injury, and rare genetic neurological diseases. By bringing together cutting-edge research, we seek to provide a comprehensive overview of current trends, technological limitations, safety considerations, and promising solutions in therapeutic interventions. Special emphasis will be placed on identifying key bottlenecks and innovative approaches that could transform our understanding and implementation of these therapeutic strategies.

We look forward to receiving your contributions.

Dr. Jubayer Hossain
Guest Editor

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Keywords

  • gene and cell therapy
  • neurodegenerative diseases
  • neurodevelopmental disorders
  • neuropsychiatric conditions
  • CNS tumors
  • trauma and injury in the CNS
  • blood–brain barrier
  • neuroimmunology and immunomodulation
  • peripheral nervous system disorders
  • regenerative medicine

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Published Papers (1 paper)

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Research

25 pages, 13483 KiB  
Article
Targeting TDP-43 Proteinopathy in hiPSC-Derived Mutated hNPCs with Mitoxantrone Drugs and miRNAs
by Uzair A. Ansari, Ankita Srivastava, Ankur K. Srivastava, Abhishek Pandeya, Pankhi Vatsa, Renu Negi, Akash Singh and Aditya B. Pant
Pharmaceutics 2025, 17(4), 410; https://doi.org/10.3390/pharmaceutics17040410 - 25 Mar 2025
Viewed by 635
Abstract
Background/Objectives: TDP-43 mutation-driven Amyotrophic Lateral Sclerosis (ALS) motor neuron disease is one of the most prominent forms (approximately 97%) in cases of sporadic ALS. Dysfunctional autophagy and lysosomal function are the prime mechanisms behind ALS. Mitoxantrone (Mito), a synthetic doxorubicin analog, is an [...] Read more.
Background/Objectives: TDP-43 mutation-driven Amyotrophic Lateral Sclerosis (ALS) motor neuron disease is one of the most prominent forms (approximately 97%) in cases of sporadic ALS. Dysfunctional autophagy and lysosomal function are the prime mechanisms behind ALS. Mitoxantrone (Mito), a synthetic doxorubicin analog, is an inhibitor of DNA and RNA synthesis/repair via intercalating with nitrogenous bases and inhibiting topoisomerase II. The therapeutic potential of miRNAs associated with disease conditions has also been reported. This study explores the therapeutic potential of Mito along with miRNAs against mutated TDP-43 protein-induced proteinopathy in human-induced pluripotent stem cell (hiPSC)-derived human neural progenitor cells (hNPCs). Methods: HiPSCs mutated for TDP-43 were differentiated into hNPCs and used to explore the therapeutic potential of Mito at a concentration of 1 μM for 24 h (the identified non-cytotoxic dose). The therapeutic effects of Mito on miRNA expression and various cellular parameters such as mitochondrial dynamics, autophagy, and stress granules were assessed using the high-throughput Open Array technique, immunocytochemistry, flow cytometry, immunoblotting, and mitochondrial bioenergetic assay. Results: Mutated TDP-43 protein accumulation causes stress granule formation (G3BP1), mitochondrial bioenergetic dysfunction, SOD1 accumulation, hyperactivated autophagy, and ER stress in hNPCs. The mutated hNPCs also show dysregulation in six miRNAs (miR-543, miR-34a, miR-200c, miR-22, miR-29b, and miR-29c) in mutated hNPCs. A significant restoration of TDP-43 mutation-induced alterations could be witnessed upon the exposure of mutated hNPCs to Mito. Conclusions: Our study indicates that miR-543, miR-29b, miR-22, miR-200c, and miR-34a have antisense therapeutic potential alone and in combination with Mitoxantrone. Full article
(This article belongs to the Special Issue New Strategies in Gene and Cell Therapy for Neurological Disorders)
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