Dirucotide
A myelin fragment meant to induce tolerance in multiple sclerosis
Dirucotide is a synthetic 17-amino-acid peptide, DENPVVHFFKNIVTPRT, matching residues 82-98 of human myelin basic protein, the region the immune system attacks in many people with multiple sclerosis. Given in high intravenous doses to induce tolerance, it delayed progression in a genetically defined phase 2 subgroup, but a phase 3 trial found no benefit.
What is it?
In multiple sclerosis the immune system attacks myelin, and in patients with the HLA-DR2 haplotype, residues 82-98 of myelin basic protein are the immunodominant target for both B and T cells. The idea behind dirucotide is high-dose tolerance: giving large amounts of that exact fragment to quieten the attack. In progressive MS it produced long-term suppression of anti-myelin basic protein antibodies in the spinal fluid of many patients. Researchers have since designed linear and cyclic versions of the fragment to bind HLA-DR2 more strongly.
A 24-month phase 2 trial in 32 patients with progressive MS found no overall difference in disability (P = 0.29), but in the 20 patients with HLA-DR2 and/or DR4, dirucotide slowed progression significantly (P = 0.01).
The phase 3 trial in secondary progressive MS, enriched after its first 100 patients for DR2 or DR4 carriers, gave 500 mg or placebo every six months for two years. There were no significant differences on time to confirmed progression or any secondary endpoint, including MRI and relapse rate. It was well tolerated, but it was not approved.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Published Research
Studies of dirucotide, from their PubMed abstracts.
Phase 3 in secondary progressive MS
With 500 mg intravenously every 6 months for 2 years, there were no significant differences from placebo in time to confirmed EDSS progression or in secondary endpoints including MRI and relapse rate; it was well tolerated.
Phase 2 and the HLA subgroup
In 32 patients with progressive MS, disability over 24 months did not differ overall (P = 0.29), but in 20 patients with HLA-DR2 and/or DR4, MBP8298 slowed progression significantly (P = 0.01).
Linear and cyclic analogues
Mutant linear and cyclic analogues of dirucotide were designed and tested; a cyclic MBP82-98 bound HLA-DR2 strongly and HLA-DR4 less, and NMR described the conformations of its functional residues.
Purification
Dirucotide, a synthetic 17-amino-acid peptide drug candidate for MS, was purified by ion exchange centrifugal partition chromatography.
Side Effects & Contraindications
Reported Side Effects
From the trials above.
Contraindications & Cautions
No label; it is investigational.
Legal Status
Dirucotide is investigational.
Frequently Asked Questions
?What is dirucotide?
An investigational synthetic peptide matching residues 82-98 of myelin basic protein, given to try to induce immune tolerance in progressive multiple sclerosis.
?Did dirucotide work?
A phase 2 subgroup with HLA-DR2 or DR4 showed slower progression, but the phase 3 trial found no significant benefit on any endpoint.
?How does it compare with glatiramer?
Both are peptide-based MS approaches; glatiramer is an approved random copolymer of four amino acids, while dirucotide is one specific myelin basic protein fragment that was not approved.
?Why did the phase 3 trial focus on HLA types?
Because the phase 2 benefit appeared only in patients with HLA-DR2 and/or DR4; after the first 100 patients without those types, enrolment was limited to carriers.
?Is dirucotide available?
No. It was not approved after its phase 3 trial, so it is not available as a medicine.
?What dose was used in the trials?
Both the phase 2 and phase 3 trials gave 500 mg intravenously every six months, the phase 2 trial for 24 months and the phase 3 trial for two years.
?What did the phase 3 trial measure?
Time to disability progression of at least 1.0 EDSS point (0.5 if baseline EDSS was 5.5 or higher), confirmed six months later, plus changes in EDSS, the MS Functional Composite, MRI, relapse rate and quality of life.
References
- [clinical-trial] Freedman MS, et al. "A phase III study evaluating the efficacy and safety of MBP8298 in secondary progressive MS." Neurology, 2011;77(16):1551-60. PMID: 21975206.
- [clinical-trial] Warren KG, et al. "Intravenous synthetic peptide MBP8298 delayed disease progression in an HLA Class II-defined cohort of patients with progressive multiple sclerosis: results of a 24-month double-blind placebo-controlled clinical trial and 5 years of follow-up treatment." Eur J Neurol, 2006;13(8):887-95. PMID: 16879301.
- [pubmed] Deraos G, et al. "Design of Linear and Cyclic Mutant Analogues of Dirucotide Peptide (MBP(82⁻98)) against Multiple Sclerosis: Conformational and Binding Studies to MHC Class II." Brain Sci, 2018;8(12). PMID: 30518150.
- [pubmed] Boudesocque L, et al. "Purification of dirucotide, a synthetic 17-aminoacid peptide, by ion exchange centrifugal partition chromatography." J Chromatogr A, 2017;1513:78-83. PMID: 28739271.
Sources & Citations
Studies were read from their PubMed records, October 3, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.