Natalizumab: What It Is, How It Works, and Alternatives for MS Treatment

When you hear natalizumab, a monoclonal antibody used to treat multiple sclerosis by blocking immune cells from entering the brain and spinal cord. Also known as Tysabri, it's not a cure—but for many people with relapsing forms of MS, it dramatically reduces flare-ups and slows disability progression. Unlike older MS drugs that work broadly across the immune system, natalizumab targets just one pathway: the molecule that lets white blood cells cross into the central nervous system. That precision is why it works so well—but also why it carries serious risks.

The biggest concern with natalizumab is PML, a rare but often fatal brain infection caused by the JC virus. It’s not common—about 1 in 1,000 patients on long-term treatment—but once it happens, there’s little doctors can do. That’s why doctors check your JC virus antibody status before starting and monitor you closely. If you’ve had prior immunosuppressant use or test positive for JC virus, your risk jumps. That’s where alternatives like fingolimod, an oral drug that traps immune cells in lymph nodes, or ocrelizumab, a different monoclonal antibody that targets B cells, come in. They don’t carry the same PML risk, though each has its own side effect profile—like heart rhythm changes with fingolimod or infusion reactions with ocrelizumab.

Natalizumab isn’t for everyone, but for some, it’s the best tool they’ve got. It’s often used after other treatments fail, or when someone has very active disease. People who respond well can go years without a relapse. But the trade-off is constant vigilance: blood tests, MRIs, and honest conversations with your neurologist about whether the benefits still outweigh the risks. If you’re on it, or considering it, knowing how it works—and what else is out there—gives you real control over your care.

Below, you’ll find detailed comparisons of natalizumab with other MS therapies, breakdowns of side effects, real-world treatment paths, and what to watch for if you’re managing this condition long-term. No fluff. Just what you need to understand your options.