Title |
Oral activity of a nature-derived cyclic peptide for the treatment of multiple sclerosis
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Published in |
Proceedings of the National Academy of Sciences of the United States of America, March 2016
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DOI | 10.1073/pnas.1519960113 |
Pubmed ID | |
Authors |
Kathrin Thell, Roland Hellinger, Emine Sahin, Paul Michenthaler, Markus Gold-Binder, Thomas Haider, Mario Kuttke, Zita Liutkevičiūtė, Ulf Göransson, Carsten Gründemann, Gernot Schabbauer, Christian W Gruber |
Abstract |
Multiple sclerosis (MS) is the most common autoimmune disease affecting the central nervous system. It is characterized by auto-reactive T cells that induce demyelination and neuronal degradation. Treatment options are still limited and several MS medications need to be administered by parenteral application but are modestly effective. Oral active drugs such as fingolimod have been weighed down by safety concerns. Consequently, there is a demand for novel, especially orally active therapeutics. Nature offers an abundance of compounds for drug discovery. Recently, the circular plant peptide kalata B1 was shown to silence T-cell proliferation in vitro in an IL-2-dependent mechanism. Owing to this promising effect, we aimed to determine in vivo activity of the cyclotide [T20K]kalata B1 using the MS mouse model experimental autoimmune encephalomyelitis (EAE). Treatment of mice with the cyclotide resulted in a significant delay and diminished symptoms of EAE by oral administration. Cyclotide application substantially impeded disease progression and did not exhibit adverse effects. Inhibition of lymphocyte proliferation and the reduction of proinflammatory cytokines, in particular IL-2, distinguish the cyclotide from other marketed drugs. Considering their stable structural topology and oral activity, cyclotides are candidates as peptide therapeutics for pharmaceutical drug development for treatment of T-cell-mediated disorders. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 4 | 14% |
Saudi Arabia | 3 | 10% |
Canada | 2 | 7% |
United Kingdom | 1 | 3% |
Australia | 1 | 3% |
Unknown | 18 | 62% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 23 | 79% |
Practitioners (doctors, other healthcare professionals) | 4 | 14% |
Scientists | 2 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Germany | 1 | <1% |
Austria | 1 | <1% |
United Kingdom | 1 | <1% |
Spain | 1 | <1% |
United States | 1 | <1% |
Unknown | 185 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 41 | 22% |
Student > Master | 29 | 15% |
Researcher | 23 | 12% |
Student > Bachelor | 13 | 7% |
Other | 11 | 6% |
Other | 33 | 17% |
Unknown | 40 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Chemistry | 38 | 20% |
Biochemistry, Genetics and Molecular Biology | 31 | 16% |
Agricultural and Biological Sciences | 18 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 15 | 8% |
Medicine and Dentistry | 14 | 7% |
Other | 27 | 14% |
Unknown | 47 | 25% |