A5026232817- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Hereditary Neurological Disorders
- Computational Drug Discovery Methods
- Amyotrophic Lateral Sclerosis Research
- Monoclonal and Polyclonal Antibodies Research
- Neurological diseases and metabolism
- biodegradable polymer synthesis and properties
- Nerve injury and regeneration
- Genetic Neurodegenerative Diseases
- Advanced Biosensing Techniques and Applications
- Botulinum Toxin and Related Neurological Disorders
- Prion Diseases and Protein Misfolding
- Carbon dioxide utilization in catalysis
- Neurogenetic and Muscular Disorders Research
- Infant Nutrition and Health
- Immune Response and Inflammation
- Complement system in diseases
- Nuclear Receptors and Signaling
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Blood groups and transfusion
- Advanced biosensing and bioanalysis techniques
- Neurological Disease Mechanisms and Treatments
- Platelet Disorders and Treatments
Light Chain Bioscience (Switzerland)
2010-2021
Brigham and Women's Hospital
2005-2008
Harvard University
2005-2006
École Polytechnique Fédérale de Lausanne
2002-2003
RAG Aktiengesellschaft (Germany)
1996
University Medical Center Freiburg
1985
Complement factor C3 is the central component of complement system and a key inflammatory protein activated in Alzheimer9s disease (AD). Previous studies demonstrated that inhibition by overexpression soluble receptor-related y an AD mouse model led to reduced microgliosis, increased amyloid β (Aβ) plaque burden, neurodegeneration. To further address role pathology, we generated C3-deficient precursor (APP) transgenic (<i>APP;C3</i><sup>−/−</sup>). Brains were analyzed at 8, 12, 17 months...
Abstract Activated microglia and reactive astrocytes invade surround cerebral β amyloid (Aβ) plaques in Alzheimer's disease (AD), but the role of plaque development is still unclear. In this study, minocycline was administered for 3 months, prior to early Aβ formation precursor protein transgenic mice (APP‐tg). When given younger mice, there a small significant increase deposition hippocampus, concurrent with improved cognitive performance relative vehicle treated mice. If APP‐tg received...
Amyloid-β (Aβ) immunotherapy lowers cerebral Aβ and improves cognition in mouse models of Alzheimer's disease (AD). A clinical trial using active immunization with Aβ1–42 was suspended after ∼6% patients developed meningoencephalitis, possibly because a T-cell reaction against Aβ. Nevertheless, beneficial effects were reported antibody responders. Consequently, alternatives are required for safer vaccine. The Aβ1–15 sequence contains the epitope(s) but lacks reactive sites full-length...
Mutations in the gene encoding superoxide dismutase 1 (SOD1) lead to misfolding and aggregation of SOD1 cause familial amyotrophic lateral sclerosis (FALS). However, implications wild-type sporadic forms ALS (SALS) remain unclear. By screening human memory B cells from a large cohort healthy elderly subjects, we generated recombinant monoclonal antibody (α-miSOD1) that selectively bound misfolded SOD1, but not physiological dimers. On postmortem spinal cord sections 121 patients with ALS,...
Abstract Non-natively folded variants of superoxide dismutase 1 (SOD1) are thought to contribute the pathogenesis familial amyotrophic lateral sclerosis (ALS), however relative toxicities these controversial. Here, we aimed decipher relationships between different SOD1 (aggregated, soluble misfolded, total) and clinical presentation ALS in G93A mouse. Using a multi-approach strategy, found that CNS regions least affected by disease had most aggregated SOD1. We also levels spinal cord were...
A bile‐acid‐binding protein of M r 14000 has been previously identified by photoaffinity labeling in rabbit ileal brush border membrane vesicles [Kramer et al. (1993) J. Biol. Chem. 268 , 18035–18046]. This peripheral membrane‐associated was purified and as an lipid‐binding protein. It further shown to be identical the cytosolic 14‐kDa from same tissue. Starting with sequence information tryptic fragments, we cloned sequenced gene its transcript. four exons (123, 176, 90, 115 bp) three...
The deposition of mutant huntingtin (mHTT) protein aggregates in neurons patients is a pathological hallmark Huntington’s disease (HD). Previous investigations cell-free and cell-based models showed mHTT exon-1 (mHTTex1) fragments with pathogenic polyglutamine (polyQ) tracts (&gt;40 glutamines) to self-assemble into highly stable, β-sheet-rich fibrillar morphology. HD knock-in mouse have not been extensively studied regard aggregation. They endogenously produce full-length polyQ tract as...
Passive immunotherapy with anti-Abeta antibodies is currently investigated for the treatment of Alzheimer's Disease several candidates in preclinical or clinical development. BIIB037 was generated using Reverse Translational Medicine method (RTM). Binding properties were measured vitro against soluble and fibrillar Abeta. In vivo studies Tg2576 mice conducted to assess brain penetration binding amyloid plaques, as well PK profile antibody. Preclinical efficacy determined after chronic dosing...
Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease characterized by motor neuron loss in the cortex, brain stem, and spinal cord. Mutations superoxide dismutase 1 (SOD1) gene, resulting misfolding of its protein product, are common cause ALS. Currently, there no approved ALS diagnostic tool. Here, we present development PET radiotracer, [
Effective passive immunotherapy of anti-beta amyloid antibodies with effector function might require antibody Fc domain-mediated brain macrophage activation subsequent phagocytosis Abeta. Herein we report that BIIB037, a murine chimeric function, appears to for plaque clearance. IgG2a recognizes conformational epitope human, fibrillar Abeta was administered intraperitoneally Tg2576 mice and compared PBS-treated controls. The area morphology vascular parenchymal plaques changes in...
The peripheral myelin protein 22 (PMP22) is highly expressed in myelinating Schwann Cells and neurons of the nervous system where it accounts for 2–5% total sheat. Minor changes PMP22 gene dosage have profound effects on development maintenance nerves. This evident from genetic disease mechanisms Charcot–Marie tooth type 1 A (CMT1A) hereditary neuropathy with liability to pressure palsies (HNPP) as well transgenic animals altered dosage. Thus, regulation a crucial aspect understanding...
Designed Ankyrin Repeat Proteins (DARPins) are thermodynamically stable, small-sized and readily expressed proteins that can be selected via display techniques against a broad set of targets. We designed DARPins various forms the Abeta peptide accumulates in brain amyloid deposits patients with Alzheimer's disease. By using ribosome approach, we peptide. Several were evaluated for their Abeta-binding potential biochemical, histological cellular assays. isolated number confirmed to...