A skin patch delivering a mixture of 3 myelin peptides significantly reduces disease activity in patients with relapsing-remitting multiple sclerosis (MS), new research shows.
The study found a significant decrease in the number of gadolinium-enhanced (Gd+) lesions as well as a significant reduction in the annual relapse rate (ARR) in patients wearing the myelin peptide patch for a year.
"The myelin peptide patch is an attractive and promising therapeutic approach," said study author Krzysztof Selmaj, MD, PhD, professor, Department of Neurology, Medical University of Lodz, Poland.
Unlike current MS drugs that inhibit a major immune function and often eliminate a wide array of immune cells, the myelin peptide patch targets MS-related antigens while sparing mechanisms critical for immune protection, Dr. Selmaj told Medscape Medical News.
The study was published online July 1 in JAMA Neurology.
Broader Treatment Implications?
The double-blind trial enrolled 30 patients with relapsing-remitting MS (22 women and 8 men), with a mean age of 36.9 years and a mean duration of illness of 8.3 years.
These patients were randomly assigned to 1 of 3 groups: placebo (n = 10); a mixture of 1 mg each of PLP139-151, MOG35-55, and MBP85-99 (n = 16); or a mixture of 10 mg each of the same 3 myelin peptides (n = 4). The treatments were delivered in an adhesive skin patch that was placed on the right upper arm and changed once a week for 4 weeks and then once per month for 11 months. The placebo patch contained phosphate-buffered saline.
This protocol was developed on the basis of experimental animal models, said Dr. Selmaj. "We're aware that it may not be optimal, and maybe in other studies we might change the pattern."
At the end of 1 year, treatment with the 1-mg patch showed a 66.5% reduction compared with placebo (0.0085 vs 0.0255) in the MRI measures of the cumulative number of Gd+ lesions per patient per scan (P = .02).
Secondary outcomes also favored the active skin patch. The mean cumulative change in volume of Gd+ lesions per patient was lower in the 1-mg group than in the placebo group (8.4 vs 13.38; P = .07). The mean cumulative number of new T2 lesions was reduced by 3-fold in the 1-mg group vs the placebo group (0.75 vs 2.4; P = .09). The mean T2 lesion volume in the 1-mg group was lower by 19.7% compared with baseline whereas in the placebo group it increased by 25.4%.
Results for the 10-mg patch were less impressive, but this may be because there were so few patients in this group, which was included primarily to determine safety. In immunology, which involves a complicated interaction between immune cells and antigens, "highest is not always better," commented Dr. Selmaj.
As for clinical outcomes, the study found that the mean AAR was significantly lower in the 1-mg myelin peptide group than in the placebo group (0.43 vs 1.4; P = .007) while the relapse-free rate was higher (63% vs 10%; P = .049). In the 1-mg patch group, 19% of patients had worsened Expanded Disability Status Scale (EDSS) scores compared with 70% in the placebo group (P = .13).
The reduced relapse activity documented in this study is matched only by that shown with natalizumab (Tysabri; Biogen Idec), a humanized monoclonal antibody approved for the treatment of MS, said Dr. Selmaj. "This is small study with only 30 patients, not 300 patients, so we need to be cautious, but if you directly compare our results with those for other drugs, our drug is attractive."
Both myelin peptide patches were safe. The most common adverse effect was a local reaction in the area of the patch. Redness and itching of modest intensity was observed in 20% of both myelin peptide patch groups. The distribution of other adverse events did not differ.
This is in contrast to current MS therapies that reduce MS activity but can put patients at risk for sometimes harmful infections. For example, natalizumab has been linked to cases of progressive multifocal leukoencephalopathy, a sometimes fatal brain infection.
The difference is likely that the myelin peptide patch is selective, said Dr. Selmaj. "Our approach just targets the immune reaction against myelin, so just the reaction directly involved in the pathogenesis of MS."
In a way, repeatedly applying myelin peptides on the skin provokes the immune system to tolerate the myelin component, said Dr. Selmaj "The autoimmune reactions which are responsible for the pathology of MS are reduced or diminished" because the immune system ceases to attack myelin components.
He likened the approach to desensitization in allergy, where exposure to allergens reduces or eliminates allergic reactions.
In theory, the approach should work for other diseases, too, said Dr. Selmaj. "The mechanisms of other autoimmune disorders are similar, so it's highly possible that other autoimmune diseases also could be affected with this therapy."
Dr. Selmaj hopes to carry out a longer study that includes more patients.
Theoretical Advantage
When asked to comment, Lily Jung Henson, MD, a neurologist at Swedish Medical Center, Seattle, Washington, said she found the study "fascinating," that it had "surprisingly good results," and was well controlled, although the number of cases is small.
"Obviously we need to see if this translates into similar efficacy and safety with larger numbers but it is really exciting from a theoretical mechanistic standpoint," said Dr. Jung Henson.
Robert Lisak, MD, chair in neurology, professor of neurology, and professor of immunology and microbiology, Wayne State University, Detroit, Michigan, was perhaps somewhat more cautious. He said that while it appears the myelin peptide patch is safe for 1 year and that the data on clinical and MRI are "certainly not discouraging, the study should be considered "very preliminary."
He pointed out that other trials have used individual myelin antigens as well as mixtures of myelin antigens given via other routes in both relapsing-remitting MS and in progressive phases. Although the therapy was safe in these studies, the results were negative, he said.
Dr. Selmaj has served on scientific advisory boards for Novartis, Biogen Idec, ONO Pharma, Genzyme, Roche, Synthon, and Teva and has received payment for lectures for Novartis, Biogen Idec, ONO Pharma, and Merck Serono.
JAMA Neurol. Published online July 1, 2013. Full text
Medscape Medical News © 2013 WebMD, LLC
Send comments and news tips to news@medscape.net.
Cite this: Myelin Peptide Skin Patch Safe, Reduces MS Activity - Medscape - Jul 29, 2013.
Comments