Rare Disease Report

Researchers Prove Rasmussen's Encephalitis Is An Autoimmune Disease

JUNE 18, 2018
Rachel Lutz
Elie Haddad. MD, PhD New evidence suggests that Rasmussen’s encephalitis is an autoimmune disease.

The degenerative disease most often develops in pediatric patients with unknown causes and presents with recurring epileptic seizures that resist traditional treatments. In serious cases, frequency of seizures is reduced by separating the two brain hemispheres—or removing one hemisphere altogether—and coping with the subsequent neurological consequences.

Other literature had previously suspected this autoimmune quality about the disease, also known as chronic focal encephalitis, but now, investigators from the University of Montreal have demonstrated these new results using humanized mice. Their findings were recently published in The Journal of Clinical Investigation.

The investigators explained that because it is such a rare disease, it is nearly impossible to enroll enough patients in a clinical trial. Previous studies tried to recreate the disease in primates, mice, and guinea pigs using a central nervous system biopsy, but were all unsuccessful. Therefore, for this study, they turned to humanized mice, which allow for more precise diagnoses and further the idea of personalized medicine. 

The mice were developed in laboratories in 2000 and they have been utilized in the past to model and observe other immune-mediated diseases such as idiopathic nephritic syndrome, asthma, and systemic lupus. These mice are crucial to this type of research because they lack an immune system, which makes them unable to reject the cells.

Elie Haddad, MD, PhD, used these humanized mice in his lab to introduce Rasmussen’s encephalitis.

Dr. Haddad used blood from 5 human control subjects and 7 Rasmussen’s encephalitis patients: 5 males and 3 females, aged between 8 and 51 years. The team observed the mice, which reacted just like their human counterparts. They developed what Dr. Haddad called “violent convulsions and brain necrosis” about three to four weeks after receiving the patients’ cells.

After a biopsy of the mice’s brains, the researchers observed immunological damage that mirrored the damage of human patients, and thus, they were able to prove that Rasmussen’s encephalitis has an immunological genesis.
Dr. Haddad told Rare Disease Report ® he was most surprised to learn that the human T lymphocyte can activate the mouse to reproduce the pathology of the human disease.

“This opens plenty of possibilities in terms of studying the pathophysiology of a disease, and also of testing various therapeutic strategies,” he said.

In the future, the researchers believe that they will be able to use the humanized mice to make earlier diagnoses and personalize the treatment for each pediatric patient. They hope to use the mice as patient surrogates to examine disease pathology and avoid cognitive decline and the need for brain surgery.
Because of these new findings, Dr. Haddad said that physicians may now try to increase the immunosuppressive drugs in an effort to induce a remission. In the past, using these immunotherapies (such as corticosteroids, intravenous immunoglobulins, tacrolimus, and the B cell-depleting CD20 antibody rituximab) have had conflicting long-term results, according to the investigators.

In the study, the researchers also tested a biological agent that blocks the entry of the cells into the brain, which they found to be very efficient, Dr. Haddad said. This agent may be reasonable for use in clinics when the patient cannot achieve remission without the usual therapeutic strategy, he added.
“In the future, one can envision that we could use this model to test new drugs in general or even to test new drugs for a given patient, in the mice that have been specifically humanized with this given patient’s lymphocytes. We would then perform a kind of personalized medicine,” Dr. Haddad concluded.

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