Transgenic cows programme to target rare lysosomal disease
AgResearch's transgenic cows programme will start work to produce a therapeutic protein to treat the rare lysosomal
storage disease Pompe disease, as soon as issues like intellectual property are sorted out. Their decision has won
praise from the patient advocacy group, Lysosomal Diseases New Zealand, but concern has already been expressed by LDNZ
that continued opposition from MadGE and other anti-GE groups could add further impediments.
Paul Atkinson, Science General Manager at AgResearch announced the addition of Pompe to their target list, at a
conference of families and professionals convened in Auckland over the past weekend by LDNZ. The protein for Pompe
disease will be one of four to be developed in the project recently approved by ERMA. The conference included one person
affected by Pompe disease, among the more than 90 family members and professionals attending LDNZ's first ever
conference.
Pompe disease results from an enzyme deficiency in the cells of the patient and this causes lysosomal storage of
Glycogen in the muscles of affected patients. "The consequences of this are very severe and newborn babies with this
disease die from respiratory problems or heart failure before reaching one year old", said John Forman, Chairperson of
LDNZ and Executive Director of NZORD, the New Zealand Organisation for Rare Disorders.
"Pompe also has serious impacts on the health of children with the juvenile form and they are often respirator and
wheelchair dependent in their teenage years. Adults have their mobility impaired by the disease and usually need CPAP
respirator assistance when sleeping", said Mr Forman, "but treatment of this complex disease is now possible and a
completely normal life should occur for future patients, thanks to advances in genetic modification technology".
The first trial of a genetically modified enzyme replacement therapy occurred in Holland a few years ago when protein
was extracted from the milk of transgenic rabbits and successfully treated several small babies with Pompe disease.
"This was the important proof of principle that was needed, and evidence that genetic modification was a necessary part
of the process to produce the complex enzyme. The storage was cleared from the muscles and a seriously ill and disabled
child returned to normal health", said Mr Forman.
Normal chemical drug production could not make a suitable therapeutic drug, but the transgenic rabbit project had
limitations in providing enough protein to treat larger numbers of patients. The company that is continuing the
production effort, Genzyme Corporation, is producing the enzyme replacement therapy by large scale fermentation of
genetically modified Chinese Hamster Ovary cell lines in huge industrial plants, but this method has its own
limitations. It has environmental considerations regarding disposal of large quantities of culture medium used in the
production process, and it is also extremely expensive.
"Transgenics offers good therapeutic efficiency but much better cost effectiveness, and it is vital that both these
issues are factored in", said Mr Forman. "We already have a scenario where another of the complex Lysosomal proteins has
just now been made available for the treatment of Fabry disease, but the CHO cell production process means it is
extremely expensive at about $250,000 per patient per year.
"Transgenic cows offer one of the best prospects for getting the right protein structures in the enzyme to make them
effective in treating the patient, and at the same time producing them at a cost that should ensure availability to all
patients in the world", said Mr Forman.
LDNZ hope that groups like MadGE will not make any further attempts to impede the AgResearch transgenic cows programme.
"I wish they could understand that without these innovative experiments in production methods, effective and affordable
treatments will not be available to patients", said Mr Forman. "If they do manage to stop the project, it will mean that
instead of Pompe disease killing newborn babies and affected children and adults in the future, it will be the actions
of ill-informed opponents like MadGE that will be responsible for the deaths by the halt they put on the technology".