Have an interesting question....Antegren prevents the VL4 "bad guy" from crossing the BB barrier and attacking the myelin but is the VL4 needed to combat any other possible disease that may decide to lurk in one's brain?
Good question, and it looks like they may have been studying this all along (I guess I'm not surprised).
alpha-4 Integrins as Therapeutic Targets in Autoimmune Disease
von Andrian U. H., Engelhardt B.
Extract | Full Text | PDF
N Engl J Med 2003; 348:68-72, Jan 2, 2003. Editorials
"Chronic inhibition of 4 integrins could also have undesirable effects that are independent of the immunogenicity of the pharmacologic inhibitor. For example, in mice, an embryonic deficiency in the 4 or 1 integrin chain or in VCAM-1 is lethal before birth,3 suggesting that the use of agents that inhibit these pathways should be avoided during pregnancy. On the other hand, in the clinical trials reported by Miller et al. and Ghosh et al., the rate of adverse events did not differ significantly between the natalizumab and placebo groups.1,2 Considering the physiologic role of 4 integrins in hematopoiesis and in mucosal and humoral immunity in animals, this finding is somewhat surprising. The recipients of natalizumab had elevated levels of lymphocytes, monocytes, and eosinophils in the circulation, which is consistent with the expression of 4 integrins on these leukocytes, whereas neutrophil levels did not change.1,2 This suggests that the antibody did not interfere with neutrophil functions that are independent of 4 integrins and are necessary to combat bacterial and fungal infections. The natalizumab-treated patients with multiple sclerosis did have a higher incidence of infections, especially pharyngitis, than the patients who received placebo, but that trend was not statistically significant. Given the small number of patients and the relatively short duration of natalizumab treatment in the current phase 2 trials, firm conclusions about the safety of 4-integrin inhibition must await the results of much larger, phase 3 studies. "
According to Company press releases and NEJM January 2003 articles, side effects of Antegren have been minimal (obviously, what is minimal is dependent on the individual).
"Adverse events occurring in at least 5 percent of natalizumab-treated patients that were 2 percent more common than in placebo-treated patients included headache, fatigue and arthralgia. The overall incidence of infection was similar between the groups. Serious infections occurred in 1 percent of placebo-treated patients and 2 percent of natalizumab-treated patients. Serious hypersensitivity-like reactions occurred in approximately 1 percent of natalizumab-treated patients."
from the January 2003 NEJM:
A Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis
Miller D. H., Khan O. A., Sheremata W. A., Blumhardt L. D., Rice G. P.A., Libonati M. A., Willmer-Hulme A. J., Dalton C. M., Miszkiel K. A., O'Connor P. W., the International Natalizumab Multiple Sclerosis Trial Group
Abstract | Full Text | PDF
N Engl J Med 2003; 348:15-23, Jan 2, 2003. Original Articles
"Monthly infusions of natalizumab for six months were well tolerated and were associated with a safety profile similar to that of placebo. There was a trend toward an increased rate of infections in the natalizumab-treated patients, the clinical significance of which is unclear."
So, in the end, we'll see what the FDA and the P3 results show. But the fact remains that over 2800 patients, side effects noted have been minimal (according to BIIB/ELN). And reduction in relapse rates have been reported of 66% and lesion load reduction (in P2) of 90+%. WELL WORTH PURSUING, I'D SAY.