A5033860761- Neurogenetic and Muscular Disorders Research
- Alzheimer's disease research and treatments
- RNA modifications and cancer
- Computational Drug Discovery Methods
- Cholinesterase and Neurodegenerative Diseases
- Glioma Diagnosis and Treatment
- RNA Research and Splicing
- Congenital Anomalies and Fetal Surgery
- Prion Diseases and Protein Misfolding
- Crystallization and Solubility Studies
- RNA Interference and Gene Delivery
- X-ray Diffraction in Crystallography
- CAR-T cell therapy research
- Muscle Physiology and Disorders
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Nuclear Receptors and Signaling
- Neuroscience and Neuropharmacology Research
- Heart Failure Treatment and Management
- Protein Interaction Studies and Fluorescence Analysis
- Chemical Reactions and Isotopes
- Retinal Imaging and Analysis
- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
Mass General Brigham
2021-2024
Cytel (United States)
2016
Film Independent
2014
Pfizer (United States)
2008-2013
Spinal Muscular Atrophy Foundation
2011-2013
Sunesis (United States)
2005-2008
Age-related macular degeneration (AMD) is a leading cause of visual dysfunction worldwide. Amyloid β (Aβ) peptides, Aβ1–40 (Aβ40) and Aβ1–42 (Aβ42), have been implicated previously in the AMD disease process. Consistent with pathogenic role for Aβ, we show here that mouse model invokes multiple factors are known to modify risk (aged human apolipoprotein E 4 targeted replacement mice on high-fat, cholesterol-enriched diet) presents Aβ-containing deposits basal retinal pigmented epithelium...
The universal presence of a gene (SMN2) nearly identical to the mutated SMN1 responsible for Spinal Muscular Atrophy (SMA) has proved an enticing incentive therapeutics development. Early disappointments from putative SMN-enhancing agent clinical trials have increased interest in improving assessment SMN expression blood as early "biomarker" treatment effect.A cross-sectional, single visit, multi-center design assessed transcript and protein 108 SMA 22 age gender-matched healthy control...
Spinal muscular atrophy (SMA), a rare neuromuscular disorder, is the leading genetic cause of death in infants and toddlers. SMA caused by deletion or loss function mutation survival motor neuron 1 (SMN1) gene. In humans, second closely related gene SMN2 exists; however it codes for less stable SMN protein. recent years, significant progress has been made toward disease modifying treatments modulating pre-mRNA splicing. Herein, we describe discovery LMI070/branaplam, small molecule that...
The SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses can be deployed easily. Here, AAVCOVID-1, an adeno-associated viral (AAV), spike-gene-based vaccine candidate demonstrates potent immunogenicity mouse non-human primates following single injection confers complete from challenge macaques. Peak neutralizing antibody...
Background Spinal Muscular Atrophy (SMA) is a neurodegenerative motor neuron disorder resulting from homozygous mutation of the survival 1 (SMN1) gene. The gene product, SMN protein, functions in RNA biosynthesis all tissues. In humans, nearly identical gene, SMN2, rescues an otherwise lethal phenotype by producing small amount full-length protein. SMN2 copy number inversely correlates with disease severity. Identifying other novel biomarkers could inform clinical trial design and identify...
A number of mouse models for spinal muscular atrophy (SMA) have been genetically engineered to recapitulate the severity human SMA by using a targeted null mutation at Smn1 locus coupled with transgenic addition varying copy numbers SMN2 genes. Although this approach has useful in modeling severe and very mild SMA, model intermediate form disease would provide an additional research tool amenable drug discovery. In addition, many previously strains are multi-allelic design, containing...
Objectives Spinal Muscular Atrophy (SMA) presents challenges in (i) monitoring disease activity and predicting progression, (ii) designing trials that allow rapid assessment of candidate therapies, (iii) understanding molecular causes consequences the disease. Validated biomarkers SMA motor non-motor function would offer utility addressing these challenges. Our objectives were to discover additional markers from Biomarkers for (BforSMA) study using an immunoassay platform, validate putative...
The behavioral and biochemical impact of active immunization against human β-amyloid (Aβ) was assessed using male transgenic (Tg) mice overexpressing a mutant amyloid precursor protein (heterozygous PDAPP mice) littermate controls. Administration aggregated Aβ 42 occurred at monthly intervals from 7 months (“prevention”) or 11 (“reversal”), followed by double-blind training 16 on cued task, then serial spatial learning in water maze. Using 2 × design, with adjuvanted MPL-AF (adjuvant...
Two experiments were conducted to investigate the possibility of faster forgetting by PDAPP mice (a well-established model Alzheimer’s disease as reported Games and colleagues in an earlier paper). Experiment 1, using aged 13–16 mo, confirmed presence a deficit spatial reference memory task water maze hemizygous relative littermate controls. However, after overtraining criterion equivalent navigational performance, series retention tests revealed group. Very limited retraining was sufficient...
In amyloid precursor protein (APP) models of deposition, the amount deposits increase with mouse age. At a first approximation, extent accumulation may either reflect small excesses production over clearance that accumulate time or, alternatively, indicate steady-state equilibrium at age, reflecting instantaneous excess clearance, which increases as organism ages. To discriminate between these options, we reversibly suppressed deposition in Tg2576 mice anti-Aβ antibody 2H6, starting 8...
Objectives Genetic defects leading to the reduction of survival motor neuron protein (SMN) are a causal factor for Spinal Muscular Atrophy (SMA). While there number therapies under evaluation as potential treatments SMA, is critical lack biomarker method assessing efficacy therapeutic interventions, particularly those targeting upregulation SMN levels. Towards this end we have engaged in developing an immunoassay capable accurately measuring levels blood, specifically peripheral blood...
Objectives Survival Motor Neuron (SMN) protein levels may become key pharmacodynamic (PD) markers in spinal muscular atrophy (SMA) clinical trials. SMN peripheral blood mononuclear cells (PBMCs) can be quantified for trials using an enzyme-linked immunosorbent assay (ELISA). We developed protocols to collect, process, store and analyze these samples a standardized manner SMA studies, understand the impact of age intraindividual variability over time on PBMC signal. Methods Several variables...
Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disorder. SMA caused by homozygous loss of the SMN1 gene and retention SMN2 resulting in reduced levels full length SMN protein that are insufficient for function. Various treatments restore currently clinical trials biomarkers needed to determine response treatment. Here, we sought investigate mice a set plasma analytes, previously identified patients with correlate The goal was whether markers were altered SMNΔ7 mouse...
Summary The SARS-CoV-2 pandemic has affected more than 70 million people worldwide and resulted in over 1.5 deaths. A broad deployment of effective immunization campaigns to achieve population immunity at global scale will depend on the biological logistical attributes vaccine. Here, two adeno-associated viral (AAV)-based vaccine candidates demonstrate potent immunogenicity mouse nonhuman primates following a single injection. Peak neutralizing antibody titers remain sustained 5 months are...
Abstract Developing a comprehensive translational program for brain tumors is complex task that involves numerous challenges. These challenges include significant obstacles surrounding the delivery of pre-clinical studies, safety, clinical trial design, and routes to commercialization. Recognizing this journey difficult, in 2023 Tessa Jowell Brain Cancer Mission launched Tumor Research Novel Therapeutics Accelerator (BTR-NTA). The BTR-NTA new international accelerator provides independent...
Abstract BACKGROUND Developing a comprehensive translational programme for brain tumours involves navigating numerous challenges, including robustness of preclinical studies, safety, clinical trial design, regulatory issues, and commercialisation. Recognising this journey can be difficult, the Brain Tumour Research Novel Therapeutics Accelerator (BTR-NTA) was launched. The BTR-NTA is an accelerator that provides independent guidance to de-risk drug or device development through systematic...
Abstract BACKGROUND Developing a comprehensive translational programme for brain tumours involves navigating numerous challenges, including robustness of preclinical studies, clinical trial design, safety, understanding and addressing regulatory requirements, commercialisation. Recognising the difficulty this journey, Brain Tumour Research Novel Therapeutics Accelerator (BTR-NTA) was launched in 2023. The BTR-NTA is an accelerator providing independent expert guidance to de-risk drug or...