Stanford Multiple Sclerosis and Neuroimmunology Research

Over decades, Stanford researchers have garnered international recognition for key discoveries about the mechanisms of action of neuroimmunological disorders, and for using those findings to expand the range of therapies for those disorders. In addition to creating a strong program in multiple sclerosis research, investigators in the division conduct research on many other disorders such as myasthenia gravis, the leukodystrophies, paraneoplastic disease, Guillain Barre syndrome, the affect of cancer on brain function and the interaction of the blood coagulation cascade with the nervous system.

In recent years, Stanford has used its extensive MS tissue bank to catalog thousands of mRNAs and proteins that are involved in the progression of the disease. The researchers have found proteins whose presence is characteristic of each of the three main stages of disease: the acute stage, the chronic-active stage and the chronic silent stage. Blocking some of these proteins leads to improvement in a mouse model of MS.

Identification and characterization of proteins involved in MS has led to a new understanding of relapse and remission of MS. Stanford researchers identified the protein Osteopontin, and showed that it played a key role in the relapse of MS by binding to a4ß1 integrin to simulate the production of cytokines and inhibit apoptosis. Lawrence Steinman, MD and his colleagues also made important discoveries about aB Crystallin. Steinman’s laboratory demonstrated that the aB Crystallin protein plays a protective role in a mouse model of multiple sclerosis. When injected in mice, it can reverse paralysis. B Crystallin is a member of the SHSP superfamily, the most widespread set of molecular chaparones. Research at Stanford and elsewhere has shown that one of the strongest immune responses in patients with multiple sclerosis is against the aB Crystallin protein. Removal of this protein accelerates the autoimmune attack against the nervous system in various ways.

Research in Steinman’s laboratory has been the foundation of the development of the most powerful drug yet approved for the relapsing and remitting form of MS, natalizumab (trade name Tysabari), which targets a4ß1 integrin. Recently Steinman also reported promising results on tests of a DNA vaccine to tame the immune system in relapsing and remitting MS. Results of the phase II clinical trials showed that the vaccine could suppress immune responses to myelin and decrease activity on brain scans. A fuller understanding of the dynamics of MS relapse and remission offers multiple possibilities for new drug targets, such osteopontin and aB Crystallin.

Stanford researchers have now discovered a molecular in the blood that discriminates who will and who will not respond to beta interferon, the most popular drug to treat relapsing MS.

Stanford researchers continue to investigate these and other possible avenues for discovering more effective MS treatments.