Can Plant Peptides Treat Multiple Sclerosis?

Research Summary: Oral activity of a nature-derived cyclic peptide for the treatment of multiple sclerosis

The background

When developing new therapies, an ideal outcome is that they will be able to be taken orally.  However, as with many multiple sclerosis medications, this often isn’t possible due to a lack of effectiveness when delivered in this way.  For this reason, many current MS therapies are taken as injectables.  Currently, three MS treatments exist that are available as oral medications (Tecfidera, Gilenya and Aubagio).   As these are often associated with a number of side-effects, there is a push to develop new oral medications for people with MS that are safer, but still effective.

Over the past 15 years, greater emphasis has been placed on identifying possible therapeutic agents derived from natural products.  All organisms contain small compounds, known as peptides, that serve a variety of different functions.  As these have evolved over thousands of years, they have often gained sophisticated and targeted functions that may have applications for health and medicine.  As an example, a peptide from a marine venomous snail has been previously identified, isolated and developed into a treatment for chronic pain.

Similar peptides have been found in plants that can suppress the immune system.  These peptides are particularly interesting, as they have a circular structure that makes them very resistant to destruction by factors in the body.  These circular peptides are known as cyclotides.  These properties have made them an interesting possibility for a new oral therapy for autoimmune diseases, such as MS.

The study

To test this, an international team led by researchers from the Medical University of Vienna investigated the use of these cyclotides to treat experimental autoimmune encephalomyelitis (EAE) – the animal model of MS.  Using this model, a number of experiments were performed to test the effectiveness of the cyclotide in various applications.

The findings

It was found that:

• Mice treated early with the cyclotide showed a significant delay in disease onset

• Mice treated with the cyclotide after they had developed partial paralysis of the limbs showed some benefit with a single injection, however, benefitted greatly from three injections administered every third day. 

• Clinical improvements were seen in mice that were treated with an oral form of the cyclotide as well.  This was seen for both of the situations described above, that is, when given prior to disease onset and after partial paralysis had developed.

• The cyclotide was also put in a head to head comparison with the currently available oral MS drug, fingolimod (Gilenya).  When given prior to disease onset, fingolimod did not improve the course of the disease, however, the cyclotide did.  Both treatments gave comparable results when three doses were given three days apart, as well as when daily doses were given.  Daily doses of fingolimod was the most effective treatment for halting progression of EAE.

The outcomes

These results are promising for the use of plant derived peptides, known as cyclotides, for the treatment of multiple sclerosis.  In the animal model of MS, they have proven to be very effective at stopping disease progression when given at a variety of times throughout the disease process.  They have also proven to be comparable, if not better, than existing oral MS medications.  As well as this, they were shown to be very safe in the animal model, with no adverse health effects reported.  This project will now need to be expanded and translated into larger trials, as well as human trials, to see whether or not these results can be replicated.

The abstract of this study can be found here.