As regular readers will know, I'm all for keeping things simple. However this is serious and in order to explain why it is serious I'm afraid that there is no option but to delve into the detail. You might want a coffee beside you at this point. OK? Right, here we go.
First stop, 2001 in that original Duke paper in
Genetics in Medicine. This paper reported the results on the 3 patients in the Duke ERT trial. Now, the actual end results - the evidence that ERT works - are not in question. The problem lies in the 'dusty end' of the paper, the Materials and Methods. Here the enzyme dosage given to the patients is described as 5mg/kg, twice weekly. Under Results, we are told that the enzyme was given for 14-17 months and again the twice-weekly 5mg/kg dosage is mentioned. There is one further reference to the dosage that I'll come to later, however the message is clear: the paper describes the results of 3 patients treated with a dosage regime of 5mg/kg, twice-weekly.
On to 2004, and the publication of a paper by Hunley
et al:
Nephrotic Syndrome Complicating α-Glucosidase Replacement Therapy for Pompe Disease
Pediatrics
Vol. 114
No. 4
October 1, 2004
(Full text available free
online)
This shares 3 authors with the 2001 paper, Drs Amalfitano, Chen and Kishnani and reports the case of a child on ERT who developed complications. However, the dosage rate is rather different from that described in the 2001 paper. This paper describes a dosage of 5mg/kg, twice-weekly (20mg every 2 weeks), for 15 weeks, followed by 10mg/kg ,twice-weekly (40mg/kg every 2 weeks)for 27 weeks, followed by 5x10mg/kg weekly (100mg per 2 weeks)for 11 weeks.
However, at no point in this paper is it explicitly stated that this patient was one of the three described in the 2001 results. So we might give Duke the benefit of the doubt (at this point, I don't think I do).
Fast forward to 2012 and the following publication from Banugaria
et al:
Persistence of high sustained antibodies to enzyme
replacement therapy despite extensive immunomodulatory therapy in an
infant with Pompe disease: Need for agents to target antibody-secreting
plasma cells
Molecular Genetics and Metabolism
Volume 105, Issue 4, April 2012, Pages 677–680
(
abstract only available free)
This papers shares 3 authors with the 2001 paper, Drs Amalfitano, Chen and Kishnani, and it refers back explicitly to one patient in that study, however the results reported are rather different. Rather than a dosage of 5mg/kg for 17 months, this paper tells us that patient 1 received: 5mg/kg twice weekly (20mg every 2 weeks)for only the first 5 months, followed by 10mg/kg twice-weekly (40mg every 2 weeks) for 8 months and then 5 X 10mg/kg weekly (100mg every 2 weeks) for 4 months.
It is fair to say then that the 2001 paper which purported to describe a treatment regime of 5/mg/kg, twice-weekly, does no such thing. On the evidence of the 2012 paper,
at least one of those patients had a much higher dosage for most of the study.
Apologies once again for all the detail. The point is to allow you to check what I've said for yourself.
Now at this point you may be thinking "OK, so the 2001 paper had wrong information in it. A simple error that any of us could have made - does it matter?" Yes, it does matter. It matters a great deal. And I shall explain why in my next post.