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Scientists are trying a revolutionary new approach to treat rheumatoid arthritis, multiple sclerosis, lupus and other devastating autoimmune diseases — by reprogramming patients’ out-of-whack immune systems.

When your body’s immune cells attack you instead of protecting you, today’s treatments tamp down the friendly fire, but they don’t fix what’s causing it. Patients face a lifetime of pricey pills, shots or infusions with serious side effects — and too often the drugs aren’t enough to keep their disease in check.

“We’re entering a new era,” said Dr. Maximilian Konig, a rheumatologist at Johns Hopkins University who’s studying some of the possible new treatments. They offer “the chance to control disease in a way we’ve never seen before.”

How? Researchers are altering dysfunctional immune systems, not just suppressing them, in a variety of ways that aim to be more potent and more precise than current therapies.

They’re highly experimental and, because of potential side effects, so far largely restricted to patients who’ve exhausted today’s treatments. But people entering early studies are grasping for hope.

Helped a lupus patient

“What the heck is wrong with my body?” Mileydy Gonzalez, 35, of New York remembers thinking, frustrated that nothing was helping her daily lupus pain.

Diagnosed at 24, her disease was worsening, attacking her lungs and kidneys. Gonzalez had trouble breathing, needed help to stand and walk and couldn’t pick up her 3-year-old son when last July, her doctor at NYU Langone Health suggested the hospital’s study using a treatment adapted from cancer: chimeric antigen receptor T-cell therapy, or CAR-T.

Gonzalez had never heard of CAR-T therapy but decided, “I’m going to trust you.” Over several months, she slowly regained energy and strength.

“I can actually run. I can chase my kid,” said Gonzalez, who now is pain- and pill-free. “I had forgotten what it was like to be me.”

‘Living drugs’ reset rogue immune systems

CAR-T therapy was developed to wipe out hard-to-treat blood cancers. But the cells that go bad in leukemias and lymphomas — immune cells called B cells — go awry in a different way in many autoimmune diseases.

Some U.S. studies in mice suggested CAR-T therapy might help with those diseases. Then in Germany, Dr. Georg Schett at the University of Erlangen-Nuremberg tried it with a severely ill young woman with lupus. After one infusion, she’s been in remission — with no other medicine — since March 2021.

Last month, Schett told a meeting of the American College of Rheumatology how his team treated a few dozen more patients with additional diseases such as myositis and scleroderma — with few relapses so far.

Those early results were “shocking,” Hopkins’ Konig recalled.

They led to an explosion of clinical trials testing CAR-T therapy in the U.S. and abroad for a growing list of autoimmune diseases.

How it works: Immune soldiers called T cells are filtered out of a patient’s blood and sent to a lab, where they’re programmed to destroy their B cell relatives. After some chemotherapy to wipe out additional immune cells, millions of copies of those “living drugs” are infused back into the patient.

While autoimmune drugs can target certain B cells, experts say they can’t get rid of those hidden deep in the body. CAR-T therapy targets both the problem B cells and healthy ones that might eventually run amok.

Other ways to reprogram rogue cells

CAR-T is grueling, time-consuming and costly, in part because it is customized. Now some companies are testing off-the-shelf versions, made in advance using cells from healthy donors.

Another approach uses “peacekeeper” cells, whose discoverers won this year’s Nobel Prize. Regulatory T cells are a rare subset of T cells that tamp down inflammation and help hold back other cells that mistakenly attack healthy tissue.

Rather than wiping out swaths of the immune system, Hopkins’ Konig aims to get more precise, targeting “only that very small population of rogue cells that really causes the damage,” he said.

Researchers in his lab are trying to engineer T cell engagers that would only mark “bad” B cells for destruction, leaving healthy ones in place to fight infection.

Stop it before it starts

Could we predict autoimmune diseases — and delay or prevent them?

A drug for Type 1 diabetes “is forging the path,” said Dr. Kevin Deane at the University of Colorado Anschutz. The drug teplizumab is approved to delay the first symptoms of diabetes, modulating rogue T cells and prolonging insulin production.

Deane studies rheumatoid arthritis (RA) and hopes to find a similar way to block the joint-destroying disease.

About 30% of people with a certain self-reactive antibody in their blood will eventually develop RA. A new study tracked some of those people for seven years, mapping immune changes leading to the disease long before joints become swollen or painful. Those changes are potential drug targets, Deane said.

On all these fronts, there’s a tremendous amount of research left to do — and no guarantees. So far, CAR-T is furthest along in testing.

“We’ve never been closer to getting to — and we don’t like to say it — a potential cure,” said Hopkins’ Konig. “I think the next 10 years will dramatically change our field forever.”

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