Calming and slowing immune cells

Teriflunomide

Immune cells that are multiplying in response to a target need a large supply of pyrimidines, building blocks of DNA. Teriflunomide blocks an enzyme called DHODH that cells use to make them. This slows the multiplying cells, while resting cells, which can recycle what they already have, are largely spared. In the TEMSO trial it reduced relapses by about a third compared with placebo.[1][2]

Because its effect is reliable and moderate, teriflunomide has become a standard comparison for newer medicines.[2]

Fumarates

Dimethyl fumarate grew out of a treatment for psoriasis used in Germany, and it reduced relapses in two phase 3 trials. In laboratory studies it switches on the Nrf2 pathway, which protects cells against oxidative stress, and this raised hopes that it might also protect nerves. It also lowers the number of lymphocytes in the blood, and which of these effects matters most in MS is still debated.[3][4][5]

Older immunosuppressants

Before the newer medicines, doctors used drugs that suppress the immune system broadly. Mitoxantrone, a cancer drug, slowed disability in a trial of people with worsening relapsing or secondary progressive MS, but its use is limited by the risk of heart damage and of leukaemia.[6][7]

Ideas that made MS worse

Some medicines that work well in other immune diseases failed in MS or made it worse. Blocking tumour necrosis factor, a mainstay of treatment for rheumatoid arthritis, increased attacks in a trial in MS. Ustekinumab, which blocks two inflammatory signals and works in psoriasis, did not reduce new lesions. Daclizumab, which targets a receptor on T cells, was approved in 2016 and withdrawn worldwide in 2018 after cases of serious brain inflammation and liver damage.[8][9][10]

These failures matter as much as the successes. They show that the immune process in MS differs from the one in arthritis or psoriasis, and that some inflammatory signals protect the nervous system as well as harm it.[8][9]