BBC Doctor Oscar details Lupus treatment meant to ‘reset’ immune system

Stem cell therapy has shown remarkable promise in treating severe autoimmune diseases, according to recent reports. A man and a woman suffering from a rare and potentially fatal autoimmune condition called neuromyelitis optica spectrum disorder (NMOSD) have remained in remission for over 15 years after undergoing a stem-cell transplant. This groundbreaking result, detailed in a study published in *Med*, suggests that such experimental treatments could be worth exploring further through larger clinical trials, according to scientists involved in the research.

NMOSD is characterized by immune cells producing antibodies that attack the spinal cord and the optic nerves, resulting in severe symptoms such as eye pain, vision loss, vomiting, and weakness or paralysis in the limbs. These symptoms typically occur in episodic bursts lasting days or months. While existing treatments can help manage these flare-ups using continuous medication, they proved ineffective for the two individuals involved in this case. Following the stem-cell transplant, both patients experienced significant improvements in their health. The man regained full neurological function, resumed a normal lifestyle, and even fathered two children. The woman regained the ability to use her arms more effectively and no longer required medication to control her symptoms.

Jiao Jiao Li, a biomedical engineer at the University of Technology Sydney, noted that although the treatment does not constitute a definitive cure, it has successfully addressed the issues caused by the disease over an extended period. The procedure employed, known as an allogeneic hematopoietic stem-cell transplant, involves collecting stem cells from a donor and infusing them into the patient. This method has previously been used to treat certain cancers, sickle-cell disease, and other blood disorders. According to Massimo Filippi, a neurologist at the IRCCS San Raffaele Hospital in Milan, this marks the first application of this therapy specifically targeting NMOSD.

The man was the first participant to receive the allogeneic transplant in 2009, using stem cells donated by his sister. The following year, the woman underwent a similar procedure, receiving stem cells from an unrelated donor. Both individuals received a single infusion of their respective donors' stem cells. Bruce Milthorpe, a scientist at the University of Technology Sydney, expressed excitement about the possibility of maintaining symptom-free status for such a prolonged duration.

Prior to the transplant, the participants underwent chemotherapy involving fludarabine and treosulfan along with a monoclonal antibody drug aimed at eliminating B cells responsible for producing harmful antibodies. To prevent complications such as graft-versus-host disease—wherein donor cells attack the recipient's healthy cells—the participants also received a brief course of antibodies and immunosuppressive medications. Neither patient developed antibodies linked to NMOSD, and both established healthy immune systems, as reported by the study's authors.

According to Li, the procedure entirely replaces the individual's immune system. Unlike alternative treatments utilizing the patient's own stem cells, which merely reset the immune system, the allogeneic approach ensures complete replacement. This method may prove more effective for autoimmune conditions if the B cells generating the harmful antibodies are fully eliminated, Li added.

In addition to this breakthrough, researchers are exploring other methods to reset the immune system for managing autoimmune diseases. Dr. Oscar Duke discussed a novel treatment involving CAR T-cell therapy, which could potentially offer relief for conditions such as lupus. This therapy targets and eliminates specific immune cells responsible for autoimmune responses, though it carries risks due to the temporary removal of protective immune components. If successful, this approach could pave the way for treating other autoimmune conditions such as rheumatoid arthritis.