Myelin reactive MHC constructs trial

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Myelin reactive MHC constructs trial

Postby MSUK » Wed May 09, 2012 6:38 am

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Background. Recombinant T-cell receptor ligand 1000 (RTL1000) is a single-chain protein construct containing the outer two domains of HLA-DR2 linked to myelin-oligodendrocyte-glycoprotein- (MOG-) 35-55 peptide. Analogues of RTL1000 induce T-cell tolerance, reverse clinical and histological disease, and promote repair in experimental autoimmune encephalomyelitis (EAE) in DR2 transgenic, C57BL/6, and SJL/J mice.

Objective. Determining the maximum tolerated dose, safety, and tolerability of RTL1000 in multiple sclerosis (MS) subjects.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/2352
MS-UK - http://www.ms-uk.org/
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Re: Myelin reactive MHC constructs trial

Postby Liberation » Wed May 09, 2012 10:45 am

squiffy2 wrote:Image

Background. Recombinant T-cell receptor ligand 1000 (RTL1000) is a single-chain protein construct containing the outer two domains of HLA-DR2 linked to myelin-oligodendrocyte-glycoprotein- (MOG-) 35-55 peptide. Analogues of RTL1000 induce T-cell tolerance, reverse clinical and histological disease, and promote repair in experimental autoimmune encephalomyelitis (EAE) in DR2 transgenic, C57BL/6, and SJL/J mice.

Objective. Determining the maximum tolerated dose, safety, and tolerability of RTL1000 in multiple sclerosis (MS) subjects.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/2352


Isn't this an old story? I have not seen any information on RTL1000 since they completed their phase 1 trial back in 2009:

"Positive results for RTL1000 phase 1 Multiple Sclerosis trial
Artielle ImmunoTherapeutics, a clinical stage biopharmaceutical company announced the presentation of "Results of a Phase 1 safety study of RTL1000, a recombinant T-Cell receptor ligand specific for an immunodominant MOG peptide, in multiple sclerosis." The results were presented yesterday by one of Artielle's founding scientists, Arthur Vandenbark, Ph.D., at the Congress of the European Federation of Neurological Societies in Florence, Italy.

The presentation showed that this Phase 1 Study met its primary objective, which was to evaluate the safety profile and determine the maximum tolerated dose (MTD) of a single IV dose of RTL1000. Secondary objectives of the study were also met; these were to determine the pharmacokinetic profile of RTL1000 and assess immunologic parameters in a subset of Multiple Sclerosis (MS) patients. This was a first-in-human, double-blind, placebo controlled trial that enrolled 34 subjects with relapsing-remitting and secondary progressive MS at six centers in the United States. All subjects were followed for clinical and MRI changes, pharmacokinetics and cytokine levels in plasma and blood mononuclear cells.

According to Dr. Arthur Vandenbark, "This trial demonstrated that RTL1000 was safe and did not exacerbate MS disease activity at any of the tested doses. Although this study was not designed to assess efficacy, immunological data in a subgroup of patients indicated RTL1000 was biologically active."

"The successful completion of this Phase 1 study represents a major milestone in the potential treatment of this devastating disease and in the development of our proprietary platform technology," said Dr. Al Ferro, President and CEO of Artielle ImmunoTherapeutics, Inc. "We plan to move aggressively to bring these novel, first-in-class products to the market place."

Worldwide, multiple sclerosis (MS) is thought to affect more than 2.5 million people. MS is a chronic autoimmune disease caused when T cells, part of the body's immune system, attack the central nervous system (CNS), which is made up of the brain, spinal cord and optic nerves. Symptoms may be mild, such as numbness in the limbs, or severe, such as paralysis or loss of vision. In MS, activation of these T cells triggers the release of inflammatory cytokines that lead to the destruction of the myelin, the fatty substance that surrounds and protects the nerve fibers in the central nervous system. When any part of the myelin sheath or nerve fiber is damaged or destroyed, nerve impulses traveling to and from the brain and spinal cord are distorted or interrupted, producing the variety of symptoms that can occur.

As demonstrated in animal studies, RTL1000 inhibits the activation of myelin-reactive T cells, preventing the release of inflammatory cytokines and causing the release of anti-inflammatory cytokines. Artielle has also shown in models of MS that animals treated with RTL1000 demonstrate repair of the myelin sheath.

Source: Artielle ImmunoTherapeutics (15/09/09)"
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