Pigs and dogs can bridge gap between mice and humans in developing new therapies

Dec 16 2008

Human and veterinary medicine could receive a big boost through use of larger animals, especially pigs and dogs, in research, with Europe at the forefront.

There is the prospect of bringing drugs to the market more quickly at less cost, as well as accelerating progress in other forms of therapy, notably the use of stem cells in regenerative medicine. The potential in this new field was discussed at a recent workshop organised by the European Science Foundation (ESF), which called for a European pig clinic to facilitate generation and characterisation of models of human disease that would be funded within the EU's Seventh Framework programme, the main source of EU funding for research projects.

The immediate goal in the field is to establish a common standardised way of using animals with clearly defined characteristics (phenotypes), so that results can be compared across Europe. "The workshop showed that there is excellent expertise in individual labs, but the phenotypic tests need to be harmonised and standardised to facilitate comparison of results obtained in different labs," said Angelika Schnieke, one of the workshop's convenors, who holds the chair of Livestock Biotechnology at the Centre of Life Science in Weihenstephan, Germany.

Such standardisation has already been achieved for rodents, particularly the mouse, which is the most widely used animal model at present for human disease research. The extension of such a framework to pigs and dogs will bring great rewards not just for human medicine, but also for treatment of animal diseases. "Large animals offer a link between the classical rodent models and application in the clinic," said Schnieke.

"In view of the close genetic, anatomical and physiological similarities between dog and pig on the one side and human on the other, large animal models are likely to catalyse drug development." As Schnieke added, large animals would also help pursue other therapeutic avenues beyond drug development, including new medical technologies, devices and interventions. Large animals could also be used for research in a number of disease categories, including cancer, metabolic disorders such as obesity, and regenerative therapies, such as use of stem cells to replace damaged heart muscle.

The workshop focused particularly on pigs and dogs because these two animals are quite similar in scale and anatomy to humans, while serving quite complementary functions. Dogs could be used as models for studying the immediate consequences of infectious disease, while pigs could be genetically engineered to mimic certain human conditions, such as deficiencies in the immune system. In such cases pigs would be used like mice are at present to model certain aspects of human immunity or metabolic disorder, but with the advantage of being closer to us in many respects.

"A possible idea is the generation of pigs with a humanised immune system," said Schnieke. "The proof of principle has been shown in the mouse. Immune-deficient mice can be reconstituted with human immune cells and can be used to study immune reactions, for example against tissue xenografts (transplantation of tissue between species, such as pig to human). In theory this could also be possible in pigs. Therefore the generation of immune-deficient pigs is an important goal."

But further funding is required to develop suitable pig models, possibly within a European pig clinic. The workshop also discussed setting up smaller collaborative projects focussed on specific disease areas, with a view to obtaining funding from the ESF. A task force was established to pursue these goals.

The workshop Large Animal Models for Biomedicine was held in Freising, Germany, in September 2008.