"Pharmed Drug" : Medicine from GM animal is cause for concern.

[Jagannath Chatterjee]

FROM GMWATCH:

 

Recently the first medicine produced from a genetically modified animal
was recommended for use in Europe. (see 'Go-ahead for 'pharmed' goat
drug')
http://news.bbc.co.uk/1/hi/sci/tech/5041298.stm

The European Medicines Agency (EMEA) reversed an earlier decision not
to issue a licence for the drug, ATryn, which is extracted from the milk
of goats engineered to carry a human gene involved in inhibiting blood
clots.

But this editorial, taken from the staunchly pro-GM journal Nature
Biotechnology, about EMEA's original decision to turn down the Atryn
application back in February, raises some interesting concerns about this
kind of transgenic product.

EXCERPT:  "The problem is that it is pretty difficult for transgenics
producers to produce 'nature-identical' proteins in milk. In cows and
sheep and GTC's bioreactor of choice, the goat, the oligosaccharide
decoration on proteins typically contains N-glycolylneuraminic acid (NGNA),
a monomer virtually absent in native human proteins... In fact, only in
rabbits and chickens are the oligosaccharides more human-like...

Thus, if immunogenicity of milk-produced proteins turns out to be a
generic problem, then a whole class of transgenic production methods may
turn out to have a limited future. Chicken milk, anyone?"
---
EDITORIAL
Nature Biotechnology 24, 368 (2006)
doi:10.1038/nbt0406-368b
http://www.nature.com/nbt/journal/v24/n4/full/nbt0406-368b.html

Transgenic milk prospects turn sour

The European Medicines Agency's (EMEA) decision back in February on
recombinant human antithrombin- , an anticoagulant developed by GTC
Biotherapeutics, was eagerly awaited because the product, known as Atryn, if
approved, would be the first drug produced in a transgenic farm animal
to reach the market. In the event, the EMEA did not approve the
product, but not because of any direct concerns about its animal origins.
Atryn was rejected because GTC simply did not present enough appropriate
data to allay EMEA's concerns about its immunogenicity.

GTC has been developing Atryn since 1993 principally for treating
patients suffering from hereditary antithrombin deficiency, a rare condition
affecting one person in every 3,000–5,000 that puts them at increased
risk of deep vein thrombosis. Over the years, Atryn has been given to
over 200 patients. But in its submission GTC only presented data on 14
patients. This exceeds the minimum requirement of 12 laid out in the EMEA
guidelines, but the authorities disallowed all but five of the cases on
the basis that GTC's dosing regimen across the group of 14 had not been
constant. GTC will appeal the decision. Ultimately, it may seek
approval instead in the United States, where the compound is now in three
phase 3 trials.

That bare-bones 'not enough data' conclusion rather skirts round some
of the underlying issues that transgenic protein producers have to face.

Recombinant proteins produced in animals typically have altered
glycosylation patterns compared with native proteins. This doesn't necessarily
influence their pharmacological properties, of course, but in the case
of Atryn, it clearly did. Compared with the conventional
antithrombin-product, which is extracted from bovine plasma, Atryn's serum half-life
was reduced seven- to tenfold, necessitating infusion of the protein
rather than a one-off injection.

But one of EMEA's principle concerns with Atryn was its potential
immunogenicity. GTC claims that it has not observed adverse immunogenicity
in any of the 200 patients who have received Atryn. It will be important
not only for GTC but also for other animal transgenics companies to
allay the concerns of regulators on this matter. The problem is that it is
pretty difficult for transgenics producers to produce
'nature-identical' proteins in milk. In cows and sheep and GTC's bioreactor of choice,
the goat, the oligosaccharide decoration on proteins typically contains
N-glycolylneuraminic acid (NGNA), a monomer virtually absent in native
human proteins. Furthermore, the high concentrations of protein
produced in milk—around a gram per liter—stretches the glycosylation capacity
of the mammary gland to its limits. In fact, only in rabbits and
chickens are the oligosaccharides more human-like (containing
N-acetylneuraminic acid).

Thus, if immunogenicity of milk-produced proteins turns out to be a
generic problem, then a whole class of transgenic production methods may
turn out to have a limited future. Chicken milk, anyone?




----------------------------------------------------------

"Our ideal is not the spirituality that withdraws from life but the conquest of life by the power of the spirit." -  Aurobindo.

__________________________________________________
Do You Yahoo!?
Tired of spam? Yahoo! Mail has the best spam protection around
http://mail.yahoo.com