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Interesting -- I wonder if they will test this for MS. I wonder how similar it is to Aimspro.



Using goats to solve autoimmundisease

July 26, 2005 -- Checkbiotech -- People suffering from autoimmune disorders, such as rheumatoid arthritis, psoriasis or multiple sclerosis, may be aided in the future: Merrimack Pharmaceuticals, Inc. is developing MM-093, a recombinant version of human á-Fetoprotein (hAFP), which is believed to have a beneficial impact on many autoimmune disorders. The twist is that Merrimack’s strategic manufacturing partner, GTC Biotherapeutics, is producing MM-093 in the milk of transgenic goats.

The glycoprotein called human á-Fetoprotein (AFP) is constitutively produced at low levels throughout life. In the fetus’ blood, there are about five microgram AFP per milliliter. Since fetal AFP enters the maternal bloodstream, pregnant women have a maximal concentration of 300 – 500 nanogram per milliliter during the third trimester of pregnancy. It is known that during pregnancy, especially during the last three months, several autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis and psoriasis, go into remission.

Therefore, researchers have examined AFP for its immunomodulatory properties. The effect of AFP on rheumatoid arthritis, multiple sclerosis, myasthenia gravis and thyroiditis has been well documented in animal experiments and provides a rationale for testing MM-093 in humans. However, human clinical testing requires a great deal of properly constructed and biologically active protein. Therefore, there is need for a production system that can cost-effectively generate large amounts of MM-093.

Several experiments have shown, that recombinant AFP produced in systems such as Escherichia coli, baculovirus and yeast, has immunomodulatory properties. However, the molecule is quite large and complicated and recovery of a sufficient yield of properly folded protein can be problematic in certain systems – for example, E. coli. Thus, there was a need to investigate a novel production system and Merrimack chose to investigate the transgenic goat system with GTC Biotherapeutics (previously Genzyme Transgenics) of Framingham, Massachusetts.

GTC Biotherapeutics has developed the transgenic goat technology as a cost-effective alternative for the production of complex proteins on a large scale. The goats produce the protein of interest in their milk – the goats are maintained on a high-tech farm using state-of-the-art animal husbandry techniques and procedures and milked using standard processes that would be employed on a dairy farm.

Merrimack then developed a process to purify MM-093 out of the goat milk and performed a battery of tests to demonstrate that it was highly comparable to human AFP (M. H. Parker et al,. 2004. Purification and characterization of recombinant human alpha-fetoprotein expressed in the milk of genetically modified goats. Protein Expression and Purification. 38:177-183.)

Once the goat milk is filtered to remove milk fat and milk proteins – essentially creating “extreme” skim milk – the purification process is very similar to purification of proteins from any other production system. The process involves standard chromatography-based purification steps that remove contaminants. The development team demonstrated that MM-093 and hAFP were virtually identical using several analytical techniques to evaluate primary, secondary and tertiary structure. In addition, the biological activity of MM-093 produced in transgenic goats was tested using cell binding assays and in animal models of disease and MM093 was determined to be biological active.

Merrimack has tested MM-093 produced in transgenic goats in Phase 1 human clinical trials and is currently testing MM-093 in a large clinical trial of rheumatoid arthritis patients who do not receive adequate relief from current therapies. Like most other therapeutic proteins, MM-093 is administered to these patients by a subcutaneous injection.

While sometimes joked about, it is important to note that it is not possible to use goat milk or goat cheese therapeutically, as the management of the goats, and the goat products, are strictly regulated by multiple government agencies. The goats are handled with the utmost care and neither the goats nor their milk will ever end up in the food chain.

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