IFN-beta and Campath shown to have neuroprotective effects

The main strategy in treating MS so far has been to dampen inflammation in hopes of limiting damage to oligodendrocytes and neurons. A complementary approach would be to protect these cells by making them more resistant to damage or more capable of repair. The latest research indicates that both of these goals can be addressed at the same time -- several MS therapies seem to reduce inflammation while simultaneously promoting neuroprotection. In past studies, glatiramer acetate (Copaxone) has been reported to stimulate production of nerve growth factors such as brain-derived neurotrophic factor (BDNF). These factors are produced in the nervous system but can also be expressed by immune cells. Now two new studies suggest similar effects for interferon-beta and for the experimental drug alemtuzumab.

The IFN-beta results come from a study done in Japan that analyzed serum BDNF levels and T cell BDNF production over time in people with MS and controls. Previous studies have examined the effect of IFN-beta on neurotrophic factors and have produced mixed results, but this question had not been studied in Asian people before. The research team found that BDNF levels in serum are higher in people with MS compared with healthy controls, are highest in the youngest people with MS who have low disease activity, and decline with age in people with MS (whereas they increase with age in healthy controls). A few of the MS subjects went on IFN-beta during the study. Treatment was accompanied by an increase in serum BDNF levels in the subjects deemed "responders" based on relapses and progression. The two non-responders had the lowest post-treatment serum BDNF levels and one of these even had a lower level post-treatment than pre-treatment. BDNF production by T cells was similar in MS and control subjects, but significantly higher in IFN-beta treated MS subjects than untreated ones. The size of the study was small, but the results support the idea that IFN-beta can have a beneficial neuroprotective effect, at least in some people.

Likewise, a study of Campath (alemtuzumab) showed that this drug also appears to boost the production of neurotrophic factors. Alemtuzumab wipes out T and B immune cells, thereby decreasing the potential for inflammatory attacks. However, scientists analyzing clinical trial results noticed that even subjects who had no sign of inflammatory activity at the start of the trial had a reduction in disability after starting the drug. They speculated that alemtuzumab may also have an effect on nerve growth factor production, perhaps because the population of immune cells that regenerate after the initial depletion has a more neuroprotective profile. The scientists took immune cells from people treated with alemtuzumab and stimulated the cells by exposure to myelin basic protein. These cells did indeed begin producing higher levels of BDNF and other growth factors such as ciliary neurotrophic factor. Furthermore, cultured neurons that were exposed to secretions from these stimulated cells had better growth and survival, and oligodendrocyte precursor cells were also more likely to mature and produce myelin.

Both of these studies reinforce the dual role (inflammatory and neuroprotective) of the immune system in MS. It would be interesting to find out whether yet another possible approach to treating MS would be to enhance nerve growth factor production directly in the brain. Drugs that induce the production of neurotrophic factors are in development for other neurologic diseases -- for example, a drug called Cogane that crosses the blood-brain barrier and boosts production of BDNF and glial-derived neurotrophic factor (GDNF) is being explored for use in Parkinson's. Perhaps this approach will someday put another type of weapon in our MS arsenal.