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An unhappy mature gray-haired man suffering from muscle pain near his elbow while sitting on a sofa during the day.
Myasthenia gravis is a chronic autoimmune disorder most often caused when the body’s immune system attacks a protein found where nerve cells communicate with muscles.
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Modified CAR-T Therapy Abates Myasthenia Gravis Symptoms

Trial showed that mRNA-led CAR-T therapy may be a safe and durable treatment option for this rare disease

National Institutes of Health
Published:Jun 23, 2023
|2 min read
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Evidence from a small-scale clinical trial suggests that a variation of the CAR (chimeric antigen receptor) T-cell therapy, or CAR-T, could be adapted to treat myasthenia gravis (MG), an autoimmune disorder of the nervous system. The modified CAR-T therapy offers the potential for a longer-lasting reduction in MG symptoms and was well-tolerated without significant adverse effects. 

The study, published in The Lancet Neurology, was supported by a small business grant from the National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health, and sponsored by Cartesian Therapeutics, Gaithersburg, MD.

“Repurposing a groundbreaking therapy such as CAR-T to potentially treat a neurological disorder shows the versatility of immunotherapies in instances where there are limited to no treatment options,” said Emily Caporello, PhD, director of the NINDS Small Business Program.

What happens in myasthenia gravis?

MG is a chronic autoimmune disorder most often caused when the body’s immune system attacks a protein found where nerve cells communicate with muscles. The disease is marked by muscle weakness that worsens after periods of activity and can improve somewhat after rest. Current treatments focus on controlling symptoms, primarily muscle weakness.

In the study, 14 people with generalized MG received varying doses of a modified form of CAR-T therapy, known as Descartes-08, targeting the cells responsible for producing MG-causing antibodies. The ideal dosage was determined to be once weekly for six weeks. 

Early data on the effectiveness of the treatment are promising, but additional clinical studies are needed to evaluate the therapy’s efficacy. Three patients receiving Descartes-08 showed complete or near-complete elimination of their symptoms, which continued six months following treatment. Two others no longer required chronic intravenous immunoglobulin treatment, which is currently used in some severe MG cases.

Findings of the clinical trial

The primary aim of this trial was to determine the ideal dosing for Descartes-08 that effectively reduces muscle weakness symptoms with minimal side effects. “What we saw were deep, durable responses to Descartes-08 that persisted for at least six months following treatment,” said Murat V. Kalayoglu, MD, PhD, president and CEO of Cartesian Therapeutics. “We have now begun a larger randomized, placebo-controlled study, which is the first of its kind for an engineered adoptive cell therapy.”

CAR-T therapy involves taking a patient’s T cells and reprogramming them to attack a specific target. In the case of blood cancers, the new target is the cancer itself. For MG, the target is the corrupted cells that make the damaging antibodies.

Many immunotherapies, including CAR-T, carry the risk of serious side effects that, while tolerable in the cases of advanced cancer, prohibit its use in more chronic conditions such as MG. Normally, the T cells are reprogrammed with DNA, which persists within the cells and is copied every time the cells divide. This can lead to an amplified effect and serious side effects.

To avoid side effects, Descartes-08 uses mRNA, which does not duplicate when cells divide, to reprogram the T cells. The result is a short course of treatment that is given multiple times instead of the single-dose regimen normally used in DNA-programmed CAR-T therapy.

Descartes-08 therapy is now being tested in a larger, clinical trial to determine its ability to reduce MG symptoms. Importantly, this trial will also include a placebo group, which is an important control to confirm that any observed improvement is due to the treatment rather than any unrelated effects.

- This press release was originally published on the National Institutes of Health website