Skip to PREreview
Requested PREreview

PREreview of The Many Faces of Parkinsonism: Dissecting Clinical and Molecular Overlap in Multiple System Atrophy and Parkinson's Disease

by Hardik Acharya, Piyush Peddi, Santhosh Diravidamani, and Ahmed Malik of Neuroden
Published
DOI
10.5281/zenodo.18554240
License
CC BY 4.0

Summary -> 

This paper explored parkinsonism in more depth and talked about the vast differences it can share with MSA with evidence gathered from various research methods. This paper had both strong points and some that might need to be revised. 

PROS

Abstract:

  • Clear statements of purpose, tools utilized to measure data, and background knowledge of Multiple system atrophy vs Parkinson’s Disorders

Introduction:

  • The authors clearly defined and explained subdivisions of Multiple System Atrophy (MSA)

  • They clearly described the geographical prevalence of the parkinsonian and cerebellar variants of MSA (MSA-P and MSA-C), displaying how certain groups of individuals could be more predisposed to a variant of MSA

Defining Parkinsonism in MSA: 

  • Clearly discussed the various symptoms and prognoses between MSA-P and Parkinson’s Disease

Emerging Clinical Trials 

  • Good incorporation of different clinical treatments of TSA, with emphasis on synuclein targeting

Modeling MSA and PD Using iPSCs

  • Showcased application of the iPSC model to their research to show differences between MSA and Parkinson’s disease

Divergent Therapeutic Strategies in MSA‐P, MSA‐C, and Parkinson’s Disease

  • Excellent attention to autonomic dysfunction and some medications (droxidopa, midodrine, and fludrocortisone)

  • Makes the comparison simple by using specific drug classes (levodopa, MAO-B inhibitors, COMT inhibitors, DBS).

Genomic Variability

  • Explains the main PD genes (SNCA, LRRK2, PARK7, PINK1, and GBA1) in detail and mentions a genetic influence of about 15%

Summary

  • Clear clinical differences between MSA and Parkinsonism

  • Connects clinical and imaging data with biomarker evidence

  • Acknowledges limitations in findings

Conclusion

  • Ties back well to abstract in the sense of presenting differences between MSA and PD

CONS

Abstract:

  • Specify on tailored therapeutic strategies -> is it a derivation of previous methods that have been utilized or something else entirely?

Conclusion

  • Lacks a Future Research Section

  • Lacks Keywords list

Emerging Clinical Trials 

  • Lack of elaboration on Lu AF82422 -> Same concept as TAK-341 and holds clinical significance, more recent

Understanding the Pathogenesis of MSA and PD

  • Further explain how serum neurofilament light chain and alpha synuclein seeding assays

Genomic Variability

  • Make the reference to Figure 1 more clear by using phrases like "As shown in Figure 1..."

Divergent Therapeutic Strategies in MSA‐P, MSA‐C, and Parkinson’s Disease

  • At the beginning, briefly explain that the purpose of this part is to compare the treatment approaches used by MSA-P, MSA-C, and PD.

Summary

  • Lack of data to support biomarker elevation or levodopa responsiveness

Competing interests

The authors declare that they have no competing interests.

Use of Artificial Intelligence (AI)

The authors declare that they did not use generative AI to come up with new ideas for their review.

Comments

Write a comment
  1. by Hany Akeel
    Published
    License
    CC BY 4.0

    This manuscript provides a comprehensive and well-structured overview of the clinical, molecular, and therapeutic distinctions between Multiple System Atrophy (MSA) and Parkinson’s Disease (PD), successfully integrating clinical observations with emerging molecular and genomic evidence. The authors demonstrate strong conceptual organization, particularly in explaining MSA subtypes, geographical distribution patterns, and divergent therapeutic strategies, while effectively incorporating novel research approaches such as induced pluripotent stem cell (iPSC) modeling and synuclein-targeting therapies. The discussion of autonomic dysfunction and pharmacological management is particularly clear and clinically relevant. However, several areas could be strengthened to enhance the manuscript’s scientific depth and clarity. The abstract would benefit from clarifying whether the proposed tailored therapeutic strategies represent novel treatment paradigms or adaptations of existing approaches. The section on emerging clinical trials should include expanded discussion of recently studied agents such as Lu AF82422 to improve currency and clinical relevance. Additional mechanistic explanation of biomarkers, including serum neurofilament light chain and alpha-synuclein seeding assays, would improve the translational connection between molecular findings and clinical diagnosis. The genomic variability section would benefit from clearer figure referencing to guide reader interpretation. Furthermore, the therapeutic comparison section should begin with a concise statement outlining its comparative purpose. The summary would be strengthened by including supporting quantitative or literature-based evidence regarding biomarker elevation and levodopa responsiveness. Finally, the manuscript would benefit from the inclusion of keywords and a dedicated future research section outlining emerging diagnostic tools and therapeutic targets. Addressing these revisions would substantially improve the manuscript’s clarity, completeness, and impact within neurodegenerative disease research.

    Competing interests

    The author of this comment declares that they have no competing interests.