Disease Specific Animal Models

Experimental autoimmune encephalomyelitis (EAE) is the most common animal model for MS.21 Multiple means have been utilized to generate EAE in both rats and mice (also in nonhuman primates). Usually an immune response is evoked by injecting myelin-derived protein plus adjuvant. In one EAE variant, activated Tcell clone specific for MBP is injected into rats. EAE was used very successfully for the development of the MS drug natalizumab. In this case, the EAE model was predictive not only for efficacy but also for the effective dose range for humans; not surprisingly, however, it proved to be an incomplete predictor of safety. In another case, the MS therapy glatiramer acetate was developed to exacerbate EAE, but instead ameliorated it - demonstrating how little is really known about EAE. Further, IFN-b is only modestly efficacious in the EAE model, but much more so in RRMS - illustrating discord between EAE and RRMS. Indeed, several immunological manipulations that reduced or abrogated EAE were inert in MS or caused worsening.

For SLE, there are several murine models, including an SLE-prone mouse (NZB/WF1), as well as a lupus-like mouse that overexpresses BLyS. Conversely, there is a BLyS knockout mouse that ameliorates the disease.

Experimental autoimmune neuritis (EAN) is an animal model for both acute and chronic inflammatory demyelinating polyneuropathy (i.e., GBS and CIDP, respectively). EAN can be generated in rats, mice, or rabbits, and is typically induced by injection of myelin proteins (P0, P2, PMP22, and MAG). Two other vaccination protocols have been used to develop models for GBS in Japanese white rabbits: a ganglioside vaccination protocol that elicits

Table 2 Current treatment options for autoimmune diseases of the nervous system

Pharmacotherapy

Action

Nature

Biopharmaceuticals (biologies)

Interferon ß-la (Avonex) Interferon ß-lb (ß seron) Interferon ß-la (Rebif) Natalizumab (Tysabri)

Belimumab (LymphoStat-B) Rituximab (Rituxan) Epratuzumab Alemtuzumab (Campath) GNTO 1275 J695

Daclizumab (Zenapex) MRA

Infliximab (Remicade) Adalimumab (D2E7) RG2077

Abatacept (Orencia)

Glatiramer acetate Abetimus sodium EN101

Pharmaceuticals (drugs)

Methylprednisolone

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