Therapeutic Plasma Exchange and Multiple Sclerosis Dysregulations: Focus on the Removal of Pathogenic Circulatory Factors and Altering Nerve Growth Factor and Sphingosine-1-Phosphate Plasma Levels

Round 1

Reviewer 1 Report

Tonev and Momchilova carried out review on pathogenesis and one particular therapeutic method of Multiple Sclerosis (MS), therapeutic plasma exchange (TPE). MS is well-known as an autoimmune and neurodegenerative disorder with quite complicated etiology and heterogenous symptoms and patient population, unfortunately still lacking efficient treatments. Though this manuscript provided comprehensive overview of the current knowledge on MS pathogenesis and covered recent progress with TPE, there are still several major and minor concerns remain to be improved.

1)     The manuscript is titled as ‘Therapeutic Plasma Exchange and Multiple Sclerosis dysregulations’, however, TPE only takes a comparatively minor part in the main text. In my opinion, making the pathogenesis part more concise and re-organize the section on TPE with subtitles (e.g. separating mechanism and clinical results) and even expand the section will make the main text more relevant to the title and helpful for the readers.

2)     Following up with Point1, TPE section contains figures and data from clinical studies, mainly from the authors’ work. Their work has unique features and novelty, which is important for the readers to know, however, previous work or similar work from others are also equally important to learn if someone is interested to study TPE.

3)      Fig 9-15 do not contain statistical results, which need to be added.

4)     Limitations and future directions mainly focused on TPE, might be better to move to TPE section.

5)     In the pathogenesis section, meningeal lymphocytes are not mentioned for their contribution to developing MS/EAE.

English is easy to understand but some paragraphs may need minor corrections for better understanding

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

The review paper provides valuable insights into the potential role of therapeutic plasma exchange (TPE) in the treatment of multiple sclerosis (MS) by exploring its effects on molecular mechanisms and biomarkers associated with the disease. It highlights the significance of S1P receptors, sources of plasma S1P, and the impact of TPE on NGF and S1P levels. Additionally, the paper introduces the intriguing nanomembrane-based TPE approach for managing acute demyelinating attacks in MS.

Overall, the paper is well-written and addresses its subject matter effectively. However, its length could be a potential drawback. Therefore, it would be beneficial for the authors to consider creating a summarized version of the paper to maintain reader engagement.

Furthermore, the discussion of nanomembrane-based TPE is intriguing, but additional information on the safety, feasibility, and accessibility of this technology for MS patients would enhance the paper's completeness.

NA

Author Response

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Author Response File: Author Response.pdf