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From lab bench to hope: a review of gene therapies in clinical trials for Parkinson’s disease and challenges

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Abstract

Parkinson's disease (PD) is a chronic neurological disorder that is identified by a characteristic combination of symptoms such as bradykinesia, resting tremor, rigidity, and postural instability. It is the second most common neurodegenerative disease after Alzheimer's disease and is characterized by the progressive loss of dopamine-producing neurons in the brain. Currently, available treatments for PD are symptomatic and do not prevent the disease pathology. There is growing interest in developing disease-modifying therapy that can reduce disease progression and improve patients’ quality of life. One of the promising therapeutic approaches under evaluation is gene therapy utilizing a viral vector, adeno-associated virus (AAV), to deliver transgene of interest into the central nervous system (CNS). Preclinical studies in small animals and nonhuman primates model of PD have shown promising results utilizing the gene therapy that express glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), aromatic L-amino acid decarboxylase (AADC), and glutamic acid decarboxylase (GAD). This study provides a comprehensive review of the current state of the above-mentioned gene therapies in various phases of clinical trials for PD treatment. We have highlighted the rationale for the gene-therapy approach and the findings from the preclinical and nonhuman primates studies, evaluating the therapeutic effect, dose safety, and tolerability. The challenges associated with gene therapy for heterogeneous neurodegenerative diseases, such as PD, have also been described. In conclusion, the review identifies the ongoing promising gene therapy approaches in clinical trials and provides hope for patients with PD.

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Authors and Affiliations

  1. Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA

    Julia Grote, Nikita Patel & Chad Bates

  2. Department of Foundational Sciences, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Tampa Bay Regional Campus, Clearwater, FL, USA

    Mayur S. Parmar

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J.G.: Drafting the manuscript, interpretation of data, editing, and revision.

N.P.: Drafting the manuscript, interpretation of data, editing, and revision.

C.B.: Drafting the manuscript, interpretation of data, editing, and revision.

M.S.P.: Conceptualization, supervision, drafting the manuscript, interpretation of data, editing, and revision.

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Correspondence to Mayur S. Parmar.

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Grote, J., Patel, N., Bates, C. et al. From lab bench to hope: a review of gene therapies in clinical trials for Parkinson’s disease and challenges. Neurol Sci (2024). https://doi.org/10.1007/s10072-024-07599-1

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