It ’s Time for Combination Therapies in Multiple Sclerosis

Conclusion In summary, MS?therapies that combine BBB-crossing molecules with peripherally acting MAbs should be a strategy of MS drug development. MS therapies that effectively limit or halt disease progression and improve overall treatment outcomes will need to address the disease mechanisms both inside and outside the CNS. It must also be recognized that the presence of lymphoid-follicle like structures are associated clinically with irreversible disability and, from a pathological perspective, show pronounced demyelination, microglial activation, and loss of neurites in the cerebral cortex.[14] Without addressing such fundamental pathological phenomena residing in a compartmentalized “zone” of the CNS, MS therapies will continue to have disappointing outcomes in treating worsening disability status in patients with MS. References Naismith RT, Trinkaus K, Cross AH. Phenotype and prognosis in African-Americans with multiple sclerosis: a retrospective chart review. Mult Scler. 2006;12:775–781. Pardridge WM. The blood-brain barrier: bottleneck in the brain drug development. NeuroRx. 2005;2(1):3–14. Banks WA. Characteristics of compounds that cross the blood-brain barrier. BMC Neurol. 2009;9:S3. Cheng Z, Zhang J, Liu H. Central nervous system penetration for small molecule therapeutic agents does not increase in multiple sclerosis and Alzheimer’s disease-related animal models despite reported blood-brain barrier disruption. Drug Metab Dispos. 2010;38:1355–1361. Hau...
Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Commentary Current Issue Drug Development Multiple Sclerosis Neurodegenerative Disease Neurology Neuromuscular Disease Psychopharmacology Update on Blood Brain Barrier combination therapies cyclophosphamide disability status laquin Source Type: research