Primary neuroprotection

There are 7 FDA-approved therapies for relapsing forms of multiple sclerosis (MS), and over a dozen more in various stages of development. Some of these therapies are highly effective, reducing new gadolinium-enhancing lesions on brain MRI by 90% or more compared to placebo. Along with reduced active inflammation, a concomitant slowing in progressive disability and brain atrophy has been reported with most approved therapies and many currently in development. But the slowing of disability accrual and atrophy should not be surprising with these therapies: prevention of acute injury leads to preservation of tissue, i.e., secondary neuroprotection. This bright hope for overtly inflammatory forms of MS contrasts with ongoing challenges in purely progressive forms of MS, which include primary progressive MS (PPMS) and secondary progressive MS (SPMS) without relapses. Many therapies with efficacy in relapsing MS, including interferon-β, glatiramer acetate, mitoxantrone, and rituximab, have produced disappointing results in clinical trials of purely progressive MS. Primary neuroprotection has proven to be a harder nut to crack than antiinflammation. Robust therapies to slow neurodegeneration are likewise lacking in Alzheimer, Parkinson, and other neurodegenerative diseases. One of the challenges in developing neuroprotective therapies for progressive MS is a twofold predicament: What biologic pathway should be targeted, and what imaging metric …