Oral MS Drug Derived from Plant Peptide Seen to Stop Disease Progression in Mice

Researchers, working with an animal model of multiple sclerosis (MS), discovered that oral treatment with a synthesized plant peptide, known as cyclotide, halted the progression of clinical symptoms without side effects. The finding offers new hope for the development of an easily available and orally deliverable treatment that might slow or even prevent the onset of MS.

The article, “Oral activity of a nature-derived cyclic peptide for the treatment of multiple sclerosis,” was published in the journal PNAS.

Cyclotides are plant peptides that can be recovered from a large group of plant families, such as coffee or cucurbits. The mechanism of action of these natural products was discovered three years ago by scientists at MedUni Vienna, Austria, in collaboration with researchers from Freiburg University Hospital, Germany. These peptides suppress the molecule IL-2 and, consequently, are able to stop immune T-cell division and proliferation, an attractive quality in a therapeutic agent targeting autoimmunity.

A team of researchers — from Austria, Germany, Australia and Sweden — demonstrated the peptides’ potential as an orally active T-cell-specific immunosuppressive therapeutic against MS, based on results obtained in an animal model widely used in MS research, the experimental autoimmune encephalomyelitis (EAE) mouse model. The natural drug “substantially impeded” disease progression in the animals, without adverse side effects, the authors reported in the study.

“As soon as functional neurological problems occur and an MRI (magnetic resonance imaging) scan identifies early pathological changes in the central nervous system, the drug can be given as a basic therapy. In an animal model for MS, symptoms were considerably reduced by the oral administration of cyclotides. It is therefore possible that we could extend the interval between episodes or possibly prevent an onset of the disease,” the study lead authors, Dr. Gernot Schabbauer and Dr. Christian Gruber, from the MedUni Vienna, said in a press release.

“The one-off oral administration of the active agent brought about a great improvement in symptoms,” Dr. Gruber added. “There were no further attacks of the disease. This could slow down the course of the disease in general.”

In light of such results, MedUni Vienna and Freiburg University Hospital have filled patent applications in several countries and licensed them to Cyxone, the company they established to further develop an orally active drug for MS treatment. The scientists hope to being a Phase 1 clinical trial of the drug in late 2018.

MS is an unpredictable and debilitating inflammatory central nervous system disease, characterized by neuronal demyelination, and currently affecting an estimated 2.3 million people worldwide. The disease can also be characterized by episodes or flare-ups of different frequencies, which further deteriorate a patient’s condition. Currently, there are some disease-modifying or symptomatic approved treatments, especially for relapsing-remitting MS, but such therapies have serious side effects, especially in the context of long-term treatment. Their delivery method, by intravenous administration, is also considered unattractive.