The Development of Methods of BLOTCHIP^®-MS for Peptidome: Small Samples in Tuberous Sclerosis

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear authors,

Since the manuscript format is not article and there are no data, I highly recommend authors submit it to the  journal as case report and review.

 

Author Response

Reviewer 1

Dear authors,

Since the manuscript format is not article and there are no data, I highly recommend authors submit it to the journal as case report and review.

Our Answer

First, we submitted four case reports on peptide analysis using BLOTCHIP®-MS to “biomedecines / MDPI”. However, the article was not peer-reviewed. After consulting with Mr. Tang, Editorial Manager, he suggested that we submit a review article with our peptide analysis to the Tuberous sclerosis associated review article the autism spectrum disorders. We re-titled the article: “Development of a peptidome analysis method in autism spectrum disorders associated with tuberous sclerosis”.

Would you accept our intention to submit it as a review article?

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Kunio et al. Mutations in the TSC2 gene are more likely to lead to autism spectrum disorder (ASD) than TSC1, everolimus improves ASD symptoms in TSC patients by inhibiting the mTOR pathway, and PMEL and SAM may be potential diagnostic markers. Moreover, the result is technically sounded and worthy to be published in CURRENT ISSUES IN MOLECULAR BIOLOGY.

The following are some comments and suggestions that are given to improve the manuscript:

 

Comment 1: TSC2 mutations are more common than TSC1 mutations, and ASD is more frequent in patients with TSC2 mutations, whether this means that TSC2 mutations are more likely to cause ASD.

 

Comment 2: The article mentions that everolimus interacts more effectively with mTORC2 than Rapamycin, does this explain its advantage in the treatment of TSC-related ASD?

 

Comment 3: PMEL and SAM are significantly altered in the plasma of TSC patients, and is this related to the pathophysiological mechanism of TSC?

 

Comment 4: In addition to everolimus, there are drugs or treatments that target the mTOR pathway to treat TSC-related ASD.

Author Response

Reviewer 2

Comments and Suggestions for Authors:

Kunio et al. Mutations in the TSC2 gene are more likely to lead to autism spectrum disorder (ASD) than TSC1, everolimus improves ASD symptoms in TSC patients by inhibiting the mTOR pathway, and PMEL and SAM may be potential diagnostic markers. Moreover, the result is technically sounded and worthy to be published in CURRENT ISSUES IN MOLECULAR BIOLOGY.

The following are some comments and suggestions that are given to improve the manuscript:

 

Comment 1: TSC2 mutations are more common than TSC1 mutations, and ASD is more frequent in patients with TSC2 mutations, whether this means that TSC2 mutations are more likely to cause ASD.

Our answer

We added sentences that TSC2 mutations are more common than TSC1 that　mutations, and ASD is more frequent in patients with TSC2 mutations, whether this means that TSC2 mutations are more likely to cause ASD (Kashii H et al. 2023) [13] in the section 6 as mark of green color.

 

Comment 2: The article mentions that everolimus interacts more effectively with mTORC2 than Rapamycin, does this explain its advantage in the treatment of TSC-related ASD?

Our answer

Summarizing findings indicated that everolimus demonstrated better ability than rapamycin treating subependymal giant cell astrocytoma and other tuberous sclerosis manifestations (Lu et al. 2020) [23] in the section 8 marked by green color.

 

Comment 3: PMEL and SAM are significantly altered in the plasma of TSC patients, and is this related to the pathophysiological mechanism of TSC?

Our answer

We added the following sentences on PMEL and SAM in the section 9, marked by green color

 

Comment 4: In addition to everolimus, there are drugs or treatments that target the mTOR pathway to treat TSC-related ASD.

Our answer

We added the sentences on the effect of rapamycin and anti-seizure treatment in the section 8 (Medical treatment in tuberous sclerosis) marker by green color.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Dear authors,

OK. I understand and accept your intention.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have answered all my previous questions.