Saturday, 22 October 2016

Antigen specific therapy shows nothing

CD206-Targeted Liposomal Myelin Basic Protein Peptides in Patients with Multiple SclerosisResistant to First-Line Disease-Modifying Therapies: A First-in-Human, Proof-of-Concept Dose-Escalation Study.
Belogurov A Jr, Zakharov K, Lomakin Y, Surkov K, Avtushenko S, Kruglyakov P, Smirnov I, Makshakov G, Lockshin C, Gregoriadis G, Genkin D, Gabibov A, Evdoshenko E.

Neurotherapeutics. 2016 Oct;13(4):895-904.Previously, we showed that CD206-targeted liposomal delivery of co-encapsulated immunodominant myelin basic protein (MBP) sequences MBP46-62, MBP124-139 and MBP147-170 (Xemys) suppressed experimental autoimmune encephalomyelitis in dark Agouti rats. The objective of this study was to assess the safety of Xemys in the treatment of patients with relapsing-remitting multiple sclerosis (MS) and secondary progressive MS, who failed to achieve a sustained response to first-line disease-modifying therapies. In this phase I, open-label, dose-escalating, proof-of-concept study, 20 patients with relapsing-remitting or secondary progressive MS received weekly subcutaneously injections with ascending doses of Xemys up to a total dose of 2.675 mg. Clinical examinations, including Expanded Disability Status Scale score, magnetic resonance imaging results, and serum cytokine concentrations, were assessed before the first injection and for up to 17 weeks after the final injection. Xemys was safe and well tolerated when administered for 6 weeks to a maximum single dose of 900 μg. Expanded Disability Status Scale scores and numbers of T2-weighted and new gadolinium-enhancing lesions on magnetic resonance imaging were statistically unchanged at study exit compared with baseline; nonetheless, the increase of number of active gadolinium-enhancing lesions on weeks 7 and 10 in comparison with baseline was statistically significant. During treatment, the serum concentrations of the cytokines monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and interleukin-7 decreased, whereas the level of tumor necrosis factor-α increased. These results provide evidence for the further development of Xemys as an antigen-specific, disease-modifying therapy for patients with MS.

The mannose receptor (Cluster of Differentiation 206, CD206) is a C-type lectin primarily present on the surface of macrophages and immature dendritic cells. In this study they got a liposome-a spherical vesicle having at least one lipid bilayer. The liposome can be used as a vehicle for administrationof nutrients and pharmaceutical drugs.  In this study they put myelin basic protein peptides into the liposome and it apparently inhibited EAE in rats.

So know they have put it into humans and they put it into relapsing MS and SPMS and  was given to people for 6 weeks and they looked to see what happened...and simply put they got nothing by the end of the study.

What happened in previous trials

Intravenous myelin basic protein failed in SPMS....
Subcutaneous myelin basic protein peptide...failed or made MS worse.

I am not a fan of subcutaneous immune tolerance and not a fan of myelin basic protein as a candidate antigen in MS so best keep my mouth shut,

If you were an investor with this first result in a phase I which is all about safety...encorage you to invest more, because is the therapeutic response going to get better.

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