Frank Mattner
Intercell
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Publication
Featured researches published by Frank Mattner.
Acta Neuropathologica | 2014
Markus Mandler; Elvira Valera; Edward Rockenstein; Harald Weninger; Christina Patrick; Anthony Adame; Radmila Santic; Stefanie Meindl; Benjamin Vigl; Oskar Smrzka; Achim Schneeberger; Frank Mattner; Eliezer Masliah
Immunotherapeutic approaches are currently in the spotlight for their potential as disease-modifying treatments for neurodegenerative disorders. The discovery that α-synuclein (α-syn) can transmit from cell to cell in a prion-like fashion suggests that immunization might be a viable option for the treatment of synucleinopathies. This possibility has been bolstered by the development of next-generation active vaccination technology with short peptides-AFFITOPEs® (AFF)- that do not elicit an α-syn-specific T cell response. This approach allows for the production of long term, sustained, more specific, non-cross reacting antibodies suitable for the treatment of synucleinopathies, such as Parkinson’s disease (PD). In this context, we screened a large library of peptides that mimic the C-terminus region of α-syn and discovered a novel set of AFF that identified α-syn oligomers. Next, the peptide that elicited the most specific response against α-syn (AFF 1) was selected for immunizing two different transgenic (tg) mouse models of PD and Dementia with Lewy bodies, the PDGF- and the mThy1-α-syn tg mice. Vaccination with AFF 1 resulted in high antibody titers in CSF and plasma, which crossed into the CNS and recognized α-syn aggregates. Active vaccination with AFF 1 resulted in decreased accumulation of α-syn oligomers in axons and synapses, accompanied by reduced degeneration of TH fibers in the caudo-putamen nucleus and by improvements in motor and memory deficits in both in vivo models. Clearance of α-syn involved activation of microglia and increased anti-inflammatory cytokine expression, further supporting the efficacy of this novel active vaccination approach for synucleinopathies.
Molecular Neurodegeneration | 2015
Markus Mandler; Elvira Valera; Edward Rockenstein; Michael Mante; Harald Weninger; Christina Patrick; Anthony Adame; Sabine Schmidhuber; Radmila Santic; Achim Schneeberger; Walter Schmidt; Frank Mattner; Eliezer Masliah
BackgroundMultiple system atrophy (MSA) is a neurodegenerative disease characterized by parkinsonism, ataxia and dysautonomia. Histopathologically, the hallmark of MSA is the abnormal accumulation of alpha-synuclein (α-syn) within oligodendroglial cells, leading to neuroinflammation, demyelination and neuronal death. Currently, there is no disease-modifying treatment for MSA. In this sense, we have previously shown that next-generation active vaccination technology with short peptides, AFFITOPEs®, was effective in two transgenic models of synucleinopathies at reducing behavioral deficits, α-syn accumulation and inflammation.ResultsIn this manuscript, we used the most effective AFFITOPE® (AFF 1) for immunizing MBP-α-syn transgenic mice, a model of MSA that expresses α-syn in oligodendrocytes. Vaccination with AFF 1 resulted in the production of specific anti-α-syn antibodies that crossed into the central nervous system and recognized α-syn aggregates within glial cells. Active vaccination with AFF 1 resulted in decreased accumulation of α-syn, reduced demyelination in neocortex, striatum and corpus callosum, and reduced neurodegeneration. Clearance of α-syn involved activation of microglia and reduced spreading of α-syn to astroglial cells.ConclusionsThis study further validates the efficacy of vaccination with AFFITOPEs® for ameliorating the neurodegenerative pathology in synucleinopathies.
PLOS ONE | 2015
Markus Mandler; Radmila Santic; Petra Gruber; Yeliz Cinar; Dagmar Pichler; Susanne Aileen Funke; Dieter Willbold; Achim Schneeberger; Walter Schmidt; Frank Mattner
Recent evidence suggests Alzheimer-Disease (AD) to be driven by aggregated Aß. Capitalizing on the mechanism of molecular mimicry and applying several selection layers, we screened peptide libraries for moieties inducing antibodies selectively reacting with Aß-aggregates. The technology identified a pool of peptide candidates; two, AFFITOPES AD01 and AD02, were assessed as vaccination antigens and compared to Aβ1-6, the targeted epitope. When conjugated to Keyhole Limpet Hemocyanin (KLH) and adjuvanted with aluminum, all three peptides induced Aß-targeting antibodies (Abs). In contrast to Aß1-6, AD01- or AD02-induced Abs were characterized by selectivity for aggregated forms of Aß and absence of reactivity with related molecules such as Amyloid Precursor Protein (APP)/ secreted APP-alpha (sAPPa). Administration of AFFITOPE-vaccines to APP-transgenic mice was found to reduce their cerebral amyloid burden, the associated neuropathological alterations and to improve their cognitive functions. Thus, the AFFITOME-technology delivers vaccines capable of inducing a distinct Ab response. Their features may be beneficial to AD-patients, a hypothesis currently tested within a phase-II-study.
Archive | 2001
Joerg Fritz; Frank Mattner; Wolfgang Zauner; Eszter Nagy; Michael Buschle
Archive | 2001
Frank Mattner; Wolfgang Zauner; Walter Schmidt; Michael Buschle
Archive | 2003
Michael Buschle; André Habel; Christoph Klade; Frank Mattner; Alexander Otava; Oresta Vytvytska; Wolfgang Zauner; Sandra Zinke; Helen Kirlappos
Archive | 2003
Frank Mattner; Walter Schmidt; André Habel
Archive | 2007
Jörg Fritz; Frank Mattner; Wolfgang Zauner; Michael Buschle; Alena Egyed
Neurobiology of Aging | 2012
Achim Schneeberger; Markus Mandler; Frank Mattner; Walter Schmidt
Archive | 2000
Michael Buschle; Julia-Kristina Fleitmann; Frank Mattner; Jack Melling