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      Parkinson’s Disease Drug Therapies in the Clinical Trial Pipeline: 2022 Update

      review-article
      a , b , c , d , d , d , d , *
      Journal of Parkinson's Disease
      IOS Press
      Clinical trials, studies, Parkinson’s, disease modification, neuroprotection, immunotherapy, inflammation, gene therapy

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          Abstract

          Background:

          As the international community dealt with the ongoing COVID-19 pandemic, important progress continued to be made in the development of new drug-based therapies for the neurodegenerative condition of Parkinson’s disease (PD) in 2021. This progress included both “symptomatic treatments” (ST – improves/reduces symptoms of the condition) and “disease modifying treatments” (DMT - attempts to delay/slow progression by addressing the underlying biology of PD), which can be categorised further based on their mechanisms of action and class of drug.

          Objective:

          This report continues previous efforts to provide an overview of the pharmacological therapies - both ST and DMT - in clinical trials for PD during 2021– 2022, with the aim of creating greater awareness and involvement in the clinical trial process. We also hope to stimulate collaboration amongst all stakeholders, including industry, academia, advocacy organizations, and most importantly patient community.

          Methods:

          We conducted a review of clinical trials of drug therapies for PD using trial data obtained from the ClinicalTrials.gov and World Health Organisation (WHO) registries, and performed a breakdown analysis of studies that were active as of January 31st 2022. We also assessed active drug development projects that had completed one clinical phase but were yet to start the next.

          Results:

          There was a total of 147 clinical trials registered on the ClinicalTrials.gov website as active during the period of analysis. Of these trials, 91 (62%)were investigating STs, while 56 (38%)focused on DMTs. Approximately 1/3 of the studies (34.7%; 51 trials) were in Phase 1, while over half of the trials were in Phase 2 (50.3%; 74 trials). Only 15% (22 trials) of the studies were in Phase 3, of which only 3 trials were evaluating DMTs. Novel therapeutics (42%)were the most common type of agents being tested across all phases of testing, followed by repurposed agents (34%)and reformulations (20%).

          Conclusion:

          Despite significant global health constraints, the development of new drug-based therapies for PD continued in 2021. Hopefully with a shift towards a post-pandemic world in which COVID-19 is better managed, we will see an increase in the number of clinical trials focused on drug development for PD. The need for more Phase 3 studies for DMTs remains acute.

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          Most cited references7

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          Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease

          Sickle cell disease is characterized by hemolytic anemia, pain, and progressive organ damage. A high level of erythrocyte fetal hemoglobin (HbF) comprising α- and γ-globins may ameliorate these manifestations by mitigating sickle hemoglobin polymerization and erythrocyte sickling. BCL11A is a repressor of γ-globin expression and HbF production in adult erythrocytes. Its down-regulation is a promising therapeutic strategy for induction of HbF.
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            Parkinson’s Disease Drug Therapies in the Clinical Trial Pipeline: 2020

            Background: The majority of current pharmacological treatments for Parkinson’s disease (PD) were approved for clinical use in the second half of the last century and they only provide symptomatic relief. Derivatives of these therapies continue to be explored in clinical trials, together with potentially disease modifying therapies that can slow, stop or reverse the condition. Objective: To provide an overview of the pharmacological therapies— both symptomatic and disease modifying— currently being clinically evaluated for PD, with the goal of creating greater awareness and opportunities for collaboration amongst commercial and academic researchers as well as between the research and patient communities. Methods: We conducted a review of clinical trials of drug therapies for PD using trial data obtained from the ClinicalTrials.gov database and performed a breakdown analysis of studies that were active as of January 21, 2020. Results: We identified 145 registered and ongoing clinical trials for therapeutics targeting PD, of which 51 were Phase 1 (35% of the total number of trials), 66 were Phase 2 (46% ), and 28 were Phase 3 (19% ). There were 57 trials (39% ) focused on long-term disease modifying therapies, with the remaining 88 trials (61% ) focused on therapies for symptomatic relief. A total of 50 (34% ) trials were testing repurposed therapies. Conclusion: There is a broad pipeline of both symptomatic and disease modifying therapies currently being tested in clinical trials for PD.
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              Parkinson’s Disease Drug Therapies in the Clinical Trial Pipeline: 2021 Update

              Background: Despite the COVID-19 pandemic, there has been considerable activity in the clinical development of novel and improved drug-based therapies for the neurodegenerative condition of Parkinson’s disease (PD) during 2020. The agents that were investigated can be divided into “symptomatic” (alleviating the features of the condition) and “disease modifying” (attempting to address the underlying biology of PD) treatments, ST and DMT respectively, with further categorisation possible based on mechanism of action and class of therapy. Objective: Our goal in this report was to provide an overview of the pharmacological therapies –both ST and DMT - in clinical trials for PD during 2020–2021, with the aim of creating greater awareness and involvement in the clinical trial process. We also hope to stimulate collaboration amongst commercial and academic researchers as well as between the research and patient communities. Methods: We conducted a review of clinical trials of drug therapies for PD using trial data obtained from the ClinicalTrials.gov and World Health Organisation (WHO) registries, and performed a breakdown analysis of studies that were active as of February 18th 2021. We also assessed active drug development projects that had completed one clinical phase but were yet to start the next. Results: We identified 142 trials on ClinicalTrials.gov and 14 studies on the WHO registries that met our analysis criteria. Of these 156 trials, 91 were ST and 65 were DMT, Of the 145 trials registered on ClinicalTrials.gov in our 2020 analysis, 45 fell off the list and 42 were added. Despite this change, the balance of ST to DMT; the distribution across phases; the profile of therapeutic categories; and the proportion of repurposed therapies (33.5%); all remained very similar. There are only two DMTs in phase 3, and we identified 33 in-between-phase projects. Conclusions: Despite the effects of the coronavirus pandemic, investment and effort in clinical trials for PD appears to remain strong. There has been little change in the profile of the clinical trial landscape even though, over the past year, there has been considerable change to the content of the list.
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                Author and article information

                Journal
                J Parkinsons Dis
                J Parkinsons Dis
                JPD
                Journal of Parkinson's Disease
                IOS Press (Nieuwe Hemweg 6B, 1013 BG Amsterdam, The Netherlands )
                1877-7171
                1877-718X
                06 May 2022
                24 May 2022
                2022
                : 12
                : 4
                : 1073-1082
                Affiliations
                [a ] Parkinson’s Research Advocate, Oxford, UK
                [b ] Parkinson’s Research Advocate, Marlboro, NJ, USA
                [c ] The Michael J Fox Foundation, Grand CentralStation, New York, NY, USA
                [d ] Cure Parkinson’s, London, UK
                Author notes
                [* ]Correspondence to: Simon R.W. Stott, Cure Parkinson’s, 120 New Cavendish Street, London, UK. E-mail: Simon@ 123456cureparkinsons.org.uk .
                Article
                JPD229002
                10.3233/JPD-229002
                9198738
                35527571
                4d4663a4-4a09-41d6-840a-31bd5fcf91ac
                © 2022 – The authors. Published by IOS Press

                This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 April 2022
                Categories
                Clinical Trial Highlights

                clinical trials,studies,parkinson’s,disease modification,neuroprotection,immunotherapy,inflammation,gene therapy

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