The most frequently seen type of Alzheimer´s disease is of unknown origin. However, an early onset type of the disease has been described as caused by genetic mutation. One of the mutations giving rise to early onset Alzheimer´s has become known as the Swedish mutation (APPsw). This mutation has been isolated and inserted into somatic donor cells at IHG, Aarhus University and the cells have been cloned by Hand Made Cloning at DJF, Aarhus University and in August 2007 giving rise to a litter of first generation Alzheimer´s pigs.
The pigs have been shown to carry the APPsw gene and produce the mutated APP giving rise to the disease (for further details see the article “Hemizygous minipigs produced by random gene insertion and handmade cloning express the Alzheimer´s disease-causing dominant mutation APPsw”, Transgenic Research, Jan. 2009).
The transgenic pigs have proven fertile and in 2009 several litters of second generation heterozygous piglets have been born. In 2010 homozygous pigs have been born
The advantages of the pig as a disease model
The benefit of using animals to mimic a human disease can limited by the fact that there are differences between the human physiology and e.g. the one of a mouse. Discoveries made in a mouse might therefore not be predictive of what happens in man under the same conditions. Some species are closer related than others and depending on the drug candidate in question one species will turn out to be a much better model than another.
Lately, it has been recognized that the pig is the best model of several diseases of man. This is in particular true in the case of Alzheimer´s disease as the structure of the pig brain is much more similar to that of man than it is to that of the mouse.
Several transgenic Alzheimer´s mouse-models have been generated over time, but they all fail to develop the neurodegenerative processes and brain lesions typical of man and must be considered sub-optimal models.
The business rationale behind animal models in drug development is simple: The better the predictive power of the model, the less total cost of development per approved drug, and hence the more value to the drug developer.
The transgenic Alzheimer´s pig model will provide an increased predictive power both because of its closer resemblance to man, and its specific genetically inflicted disease.