Talk:Eteplirsen

Mechanism too technical
I added some explanation to the mechanism section by inserting an initial paragraph describing exon skipping for DMD in general. JonMoulton (talk) 15:31, 28 August 2013 (UTC)
 * I've removed the {{technical flag - seems ok/wikilinked now. - Rod57 (talk) 17:57, 23 April 2016 (UTC)

FDA submission
There was news that Eteplirsen was submitted to FDA for approval. Look here. Haron2010 (talk) 18:33, 25 December 2013 (UTC)

Benefit
Ref says "Out-of-frame duplications are found in 10% of patients" and "skipping exon 51 restores the reading frame in about 15% of boys with Duchenne muscular dystrophy caused by out-of-frame deletions."

So 10% * 15% = about 1.5% Doc James  (talk · contribs · email) 20:42, 30 July 2019 (UTC)

This is an error and should be corrected. Doc James claimed that eteplirsen can only treat 1.5% of the Duchenne population based on two numbers: that 10% of patients have out-of-frame duplication, and that 15% of boys with deletions can have their reading frames restored by skipping exon 51. The problem is that these are different populations.

People with duplications are not the same as people with deletions. It is not accurate to multiply the 10% out-of-frame duplication rate prevalence by the 15% exon-51-skip treatable deletion prevalence to arrive at the 1.5% overall treatable product. These are different populations.

Here is a recent prevalence figure from a Duchenne referral center: "Among 442 cases, deletions and duplications encompassing one or more exons were identified in 270 (61%) and 38 (9%) cases, respectively."(1) 61% of DMD patients having deletions multiplied by 15% of patients with deletions being treatable by exon skipping gives 9% for the fraction of the DMD population treatable by exon 51 skipping. This is closer to reality than the currently-displayed 1.5% number at the top of the Wikipedia eteplirsen page.

One of the papers cited in the erroneous initial sentence of the Wikipedia eteplirsen page has in its abstract the statement "Eteplirsen is applicable for approximately 14% of patients with DMD mutations.". This figure from the 2017 paper (2)is based on larger patient population data than the 442 cases in the 2010 report from the Duchenne referral center. The last author, Toshifumi Yokota, holds The Friends of Garrett Cumming Research & Muscular Dystrophy Canada HM Toupin Neurological Science Endowed Research Chair at U Alberta and runs an active DMD research group.

I have altered the statement at the top of the eteplirsen page to reflect the 14%-treatable figure reported by Lim et al.

(1) Takeshima Y et al. Mutation spectrum of the dystrophin gene in 442 Duchenne/Becker muscular dystrophy cases from one Japanese referral center. J Hum Genet. 2010; 55:79–388 doi:10.1038/jhg.2010.49 https://www.nature.com/articles/jhg201049

(2) Lim KR, Maruyama R, Yokota T. Eteplirsen in the treatment of Duchenne muscular dystrophy. Drug Des Devel Ther. 2017;11:533-545. doi:10.2147/DDDT.S97635

JonMoulton (talk) 19:18, 10 October 2019 (UTC)


 * Okay looking at it further and agree you are correct. Doc James  (talk · contribs · email) 08:02, 12 October 2019 (UTC)


 * You may remove this discussion from the talk page -- it is past its usefulness now. JonMoulton (talk) 17:35, 14 October 2019 (UTC)


 * Lil, et al., state the number as 14%. Scoto, et al., have at at 0.65 × 0.15 ≈ 0.10, i.e., ~10% (that is, 15% of all those with out-of-frame deletions who in turn form 65% of all DMD patients). In view of discrepancies in sources, shouldn't we state the number in the lead less categorically? — kashmīrī  TALK  01:54, 14 December 2019 (UTC)