Name: ACI-35 Therapy Type: Immunotherapy (active)
Post# of 30066
Posted On: 02/11/2015 12:50:20 AM
Name: ACI-35
Therapy Type: Immunotherapy (active) (timeline)
Target Type: Tau (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 1)
Company: Janssen
Background
ACI-35 is a liposome-based vaccine. The rationale behind it is that the vaccine will treat tauopathy in Alzheimer’s disease by eliciting an immune response targeted to certain pathological conformers of phosphorylated tau without also mounting autoimmune B cell or T cell responses against physiological forms of this ubiquitous intracellular protein. The vaccine contains 16 copies of a synthetic tau fragment that is phosphorylated at the protein’s pathological phosphorylation residues S396 and S404 and is anchored into a lipid bilayer. It uses the adjuvant MPLA (Hickman et al., 2011, and Jun 2012 conference story).
In both wild-type C57BL/6 and P301L mutant tau transgenic mice, a three-month regimen of subcutaneous ACI-35 injection generated high titers of polyclonal IgG antibodies specifically directed against phosphorylated tau, rather than non-phosphorylated tau. The resulting antibodies were reported to bind neurofibrillary tangles in mouse brain tissue sections and to reduce soluble tau as well as insoluble, aggregated tau in brain extracts. ACI-35 also reportedly improved three of four tested clinical parameters: It increased retention of body weight, delayed onset of a clasping motor phenotype, and extended lifespan, but it did not improve endurance on a rotarod test. This preclinical study also that reported that tests of gliosis, T cell activation, and other inflammatory markers were negative (Theunis et al., 2013). Similar data in non-human primates were presented at the 2013 Society for Neuroscience conference.
In January 2015, AC Immune partnered with Johnson and Johnson to develop ACI-35.
Findings
In December 2013, AC Immune began the first human trial of a phospho-tau-specific vaccine. This Phase 1 study compares two doses of ACI-35 in people with mild to moderate AD. It is a randomized, double-blind, placebo-controlled study of safety, tolerability, and immunogenicity. It also has secondary outcomes for an initial look at biomarkers, functional outcomes, and clinical outcomes, the company said in a press release. At the 2014 AAIC conference in Copenhagen, Denmark, AC Immune CEO Andrea Pfeifer told Alzforum that trial data may be released by the end of 2014 (see Aug 2014 news story).
This trial is not listed in clinicaltrials.gov or the World Health Organization’s clinical trial registry.
As of 2014, AC Immune is partnering with Piramal Imaging to develop tau PET tracers for localization and quantification of tau pathology in the brain (see company press release). This company has bought florbetaben, now called NeuraceqTM, the amyloid imaging tracer being used in AC Immune’s clinical Phase 1/2 trial of the anti-Aβ vaccine ACI-24.
http://www.alzforum.org/therapeutics/aci-35
I'm curious if AMBS is involved at all ?
Therapy Type: Immunotherapy (active) (timeline)
Target Type: Tau (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 1)
Company: Janssen
Background
ACI-35 is a liposome-based vaccine. The rationale behind it is that the vaccine will treat tauopathy in Alzheimer’s disease by eliciting an immune response targeted to certain pathological conformers of phosphorylated tau without also mounting autoimmune B cell or T cell responses against physiological forms of this ubiquitous intracellular protein. The vaccine contains 16 copies of a synthetic tau fragment that is phosphorylated at the protein’s pathological phosphorylation residues S396 and S404 and is anchored into a lipid bilayer. It uses the adjuvant MPLA (Hickman et al., 2011, and Jun 2012 conference story).
In both wild-type C57BL/6 and P301L mutant tau transgenic mice, a three-month regimen of subcutaneous ACI-35 injection generated high titers of polyclonal IgG antibodies specifically directed against phosphorylated tau, rather than non-phosphorylated tau. The resulting antibodies were reported to bind neurofibrillary tangles in mouse brain tissue sections and to reduce soluble tau as well as insoluble, aggregated tau in brain extracts. ACI-35 also reportedly improved three of four tested clinical parameters: It increased retention of body weight, delayed onset of a clasping motor phenotype, and extended lifespan, but it did not improve endurance on a rotarod test. This preclinical study also that reported that tests of gliosis, T cell activation, and other inflammatory markers were negative (Theunis et al., 2013). Similar data in non-human primates were presented at the 2013 Society for Neuroscience conference.
In January 2015, AC Immune partnered with Johnson and Johnson to develop ACI-35.
Findings
In December 2013, AC Immune began the first human trial of a phospho-tau-specific vaccine. This Phase 1 study compares two doses of ACI-35 in people with mild to moderate AD. It is a randomized, double-blind, placebo-controlled study of safety, tolerability, and immunogenicity. It also has secondary outcomes for an initial look at biomarkers, functional outcomes, and clinical outcomes, the company said in a press release. At the 2014 AAIC conference in Copenhagen, Denmark, AC Immune CEO Andrea Pfeifer told Alzforum that trial data may be released by the end of 2014 (see Aug 2014 news story).
This trial is not listed in clinicaltrials.gov or the World Health Organization’s clinical trial registry.
As of 2014, AC Immune is partnering with Piramal Imaging to develop tau PET tracers for localization and quantification of tau pathology in the brain (see company press release). This company has bought florbetaben, now called NeuraceqTM, the amyloid imaging tracer being used in AC Immune’s clinical Phase 1/2 trial of the anti-Aβ vaccine ACI-24.
http://www.alzforum.org/therapeutics/aci-35
I'm curious if AMBS is involved at all ?
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