Reviewer ’s report  
 
Title: Transplantation, gene therapy and intestinal pathology in MNGIE patients and mice  
 
Version: 1 Date: 15 Feb 2018  
 
Reviewer: Caterina Garone  
 
Reviewer's report:  
 
Yadak R et al, studied the effect of hematopoeitic stem cell transplantation on the intestinal 
pathology of MNGIE patients and tymp -/-upp1 -/- mouse model.  
The manuscript is potentially interesting and relevant for the approach to treatment in MNGIE 
patients but the experimental plan  raise a main criticism regarding the intestinal pathology of the 
mouse model.  
The authors described in details the intestinal pathology of three patients with MNGIE disease 
reporting the absence of Cajal cells as main mechanism of gastrointestinal dysmot ility.  
However, there is lack of this information in the MNGIE mouse model. Alternative approach for 
characterising the Cajal cells (e.g immunostaining with ANO1 antibody/ alternative sample 
preparation for Kit staining) must be considered in order to sus tain the results and conclusion of 
the manuscript.  
Discussion must take into account the short follow -up and cause of death of the two treated 
patients. As reported in the cited manuscript (Halter et al, 2015) an improvement in the 
gastrointestinal sympto ms was observed after 6 months of follow -up. 
As minor revision, I would also suggest to cite figure panels  in the text for facilitating the 
reading of the manuscript.  
In conclusion, I would recommend the manuscript for publication upon major revision.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
  
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional  statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or  lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future ? 
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of th e manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
No conflict of interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publicatio n, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4. 0/). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Transplantation, gene therapy and intestinal pathology in MNGIE patients and mice  
 
Version: 1 Date: 15 Feb 2018  
 
Reviewer: Caterina Garone  
 
Reviewer's report:  
 
Yadak R et al, studied the effect of hematopoeitic stem cell transplantation on the intestinal 
pathology of MNGIE patients and tymp -/-upp1 -/- mouse model.  
The manuscript is potentially interesting and relevant for the approach to treatment in MNGIE 
patients but the experimental plan  raise a main criticism regarding the intestinal pathology of the 
mouse model.  
The authors described in details the intestinal pathology of three patients with MNGIE disease 
reporting the absence of Cajal cells as main mechanism of gastrointestinal dysmot ility.  
However, there is lack of this information in the MNGIE mouse model. Alternative approach for 
characterising the Cajal cells (e.g immunostaining with ANO1 antibody/ alternative sample 
preparation for Kit staining) must be considered in order to sus tain the results and conclusion of 
the manuscript.  
Discussion must take into account the short follow -up and cause of death of the two treated 
patients. As reported in the cited manuscript (Halter et al, 2015) an improvement in the 
gastrointestinal sympto ms was observed after 6 months of follow -up. 
As minor revision, I would also suggest to cite figure panels  in the text for facilitating the 
reading of the manuscript.  
In conclusion, I would recommend the manuscript for publication upon major revision.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
  
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional  statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or  lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future ? 
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of th e manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
No conflict of interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publicatio n, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4. 0/). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Transplantation, gene therapy and intestinal pathology in MNGIE patients and mice  
 
Version: 1 Date: 15 Feb 2018  
 
Reviewer: Caterina Garone  
 
Reviewer's report:  
 
Yadak R et al, studied the effect of hematopoeitic stem cell transplantation on the intestinal 
pathology of MNGIE patients and tymp -/-upp1 -/- mouse model.  
The manuscript is potentially interesting and relevant for the approach to treatment in MNGIE 
patients but the experimental plan  raise a main criticism regarding the intestinal pathology of the 
mouse model.  
The authors described in details the intestinal pathology of three patients with MNGIE disease 
reporting the absence of Cajal cells as main mechanism of gastrointestinal dysmot ility.  
However, there is lack of this information in the MNGIE mouse model. Alternative approach for 
characterising the Cajal cells (e.g immunostaining with ANO1 antibody/ alternative sample 
preparation for Kit staining) must be considered in order to sus tain the results and conclusion of 
the manuscript.  
Discussion must take into account the short follow -up and cause of death of the two treated 
patients. As reported in the cited manuscript (Halter et al, 2015) an improvement in the 
gastrointestinal sympto ms was observed after 6 months of follow -up. 
As minor revision, I would also suggest to cite figure panels  in the text for facilitating the 
reading of the manuscript.  
In conclusion, I would recommend the manuscript for publication upon major revision.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
  
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional  statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or  lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future ? 
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of th e manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
No conflict of interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publicatio n, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4. 0/). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant