The first medicines: interferon beta and glatiramer acetate

Interferon beta

Interferons are proteins the body makes to fight viruses. They were tried in MS partly because the disease was long suspected to have a viral cause. The first attempt went badly: in a study published in 1987, interferon gamma made MS worse, with more attacks during treatment. Interferon beta had the opposite effect. In the trial that led to its approval in 1993, the higher dose reduced relapses by about a third compared with placebo and reduced activity on MRI.[1][2]

That two interferons had opposite effects showed that the type of immune signal matters, not only the amount. Interferon beta is now thought to work by damping several inflammatory signals and reducing the movement of immune cells into the brain, rather than by fighting a virus.[3]

Glatiramer acetate

Glatiramer acetate began as an attempt to cause disease. In the late 1960s, researchers in Israel made random chains of four amino acids found in a myelin protein, hoping to use them to provoke EAE in animals. The chains protected the animals instead. The compound was developed into a daily injection and approved in the United States in 1996, after a trial showed fewer relapses than with placebo. How it works is still debated. The leading explanation is that it shifts the immune response against myelin towards a less inflammatory kind.[4][5][6][8]

What they taught researchers

Both medicines reduced relapses but did little for progression without relapses. In primary progressive MS, glatiramer acetate did not significantly slow the primary disability outcome in the PROMiSe trial. This pattern, success against relapses and little effect on steady worsening, was to repeat itself with many later medicines.[7]