A5018154365- Biotin and Related Studies
- Lysosomal Storage Disorders Research
- Click Chemistry and Applications
- Glycogen Storage Diseases and Myoclonus
- Carbohydrate Chemistry and Synthesis
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- Radiomics and Machine Learning in Medical Imaging
- Cancer Immunotherapy and Biomarkers
- Biochemical and Molecular Research
- Prenatal Screening and Diagnostics
- Ferroptosis and cancer prognosis
- Molecular Junctions and Nanostructures
- Glycosylation and Glycoproteins Research
- Cancer Cells and Metastasis
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Myasthenia Gravis and Thymoma
- Muscle Physiology and Disorders
- Genetic Syndromes and Imprinting
- Cellular transport and secretion
- Phagocytosis and Immune Regulation
- Gestational Trophoblastic Disease Studies
- Pancreatic and Hepatic Oncology Research
- Cell death mechanisms and regulation
- Hereditary Neurological Disorders
Sanofi (United States)
2016-2024
Virginia Commonwealth University Medical Center
1996-2013
Virginia Commonwealth University
1995-2013
SynZyme Technologies (United States)
2009
Analysis Group (United States)
2006-2009
Clinical Science Institute
2008
Erasmus MC
2007
Brigham and Women's Hospital
1991-1993
Pompe disease (acid maltase deficiency, glycogen storage type II; OMIM 232300) is an autosomal recessive lysosomal disorder characterized by acid alpha-glucosidase deficiency due to mutations in the GAA gene. Progressive skeletal muscle weakness affects motor and respiratory functions typical for all forms of disease. Cardiac hypertrophy additional fatal symptom classic infantile subtype. c.-32-13T-->G most common mutation adults.To delineate variation among patients with this define...
Pompe disease was named after the Dutch pathologist Dr JC who reported about a deceased infant with idiopathic hypertrophy of heart. The clinical findings were failure to thrive, generalized muscle weakness and cardio-respiratory failure. key pathologic finding massive storage glycogen in heart, skeletal many other tissues. classified as type II decades later shown be lysosomal disorder caused by acid α-glucosidase deficiency. spectrum appeared much broader than originally recognized. Adults...
Abstract RIPK1 is a master regulator of inflammatory signaling and cell death increased activity observed in human diseases, including Alzheimer’s disease (AD) amyotrophic lateral sclerosis (ALS). inhibition has been shown to protect against range preclinical cellular animal models diseases. SAR443060 (previously DNL747) selective, orally bioavailable, central nervous system (CNS)–penetrant, small‐molecule, reversible inhibitor RIPK1. In three early‐stage clinical trials healthy subjects...
Abstract Background Targeting receptor-interacting serine/threonine protein kinase 1 could mitigate the devastating sequelae of hyperinflammatory state observed in severe cases COVID-19. This study explored immunomodulatory and clinical effects inhibitor SAR443122 (eclitasertib) patients with Methods In this Phase 1b, double-blinded, placebo-controlled (NCT04469621) a total 82 were screened, whom 68 eligible randomized (2:1) to receive eclitasertib 600 mg (300 twice daily) or placebo up 14...
Pompe disease is an autosomal recessive lysosomal glycogen storage disorder, characterized by progressive muscle weakness. Deficiency of acid α-glucosidase (EC; 3.2.1.20/3) can be caused numerous pathogenic variants in the GAA gene. The Disease Mutation Database at http://www.pompecenter.nl aims to list all and their effect. This update reports on 94 variants. We examined 35 novel 34 known mutations site-directed mutagenesis transient expression COS-7 cells or HEK293T cells. Each these was...
Abstract SAR443820 (DNL788) is a selective, orally bioavailable, brain penetrant inhibitor of receptor‐interacting serine/threonine protein kinase 1 (RIPK1). This phase I first‐in‐human healthy participant study (NCT05795907) was comprised three parts: randomized, double‐blind, placebo‐controlled single ascending dose (SAD; part 1a); 14‐day multiple (MAD; 2) parts that evaluated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics SAR443820; separate open‐label, single‐dose 1b...
Biotinidase deficiency is an autosomal-recessive disorder of biotin recycling. Children with profound biotinidase usually have neurological and cutaneous symptoms in early childhood, but they may not develop until adolescence. We now report on a man woman who are asymptomatic were diagnosed only because their biotinidase-deficient children identified by newborn screening. These adults never exhibited the homozygous for two different mutations resulting aberrant enzymes. There no evidence...
Abstract SAR439459, a ‘second‐generation’ human anti‐transforming growth factor‐beta (TGFβ) monoclonal antibody, inhibits all TGFβ isoforms and improves the antitumor activity of anti‐programmed cell death protein‐1 therapeutics. This study reports pharmacodynamics (PD) biomarker results from phase I/Ib first‐in‐human SAR439459 ± cemiplimab in patients with advanced solid tumors (NCT03192345). In dose‐escalation (Part 1), was administered intravenously at increasing doses either every 2...
Background: The cellular composition of the tumor immune microenvironment (TIME) is a key contributor to response immunotherapy. Transforming growth factor-beta (TGF-β) signaling known promote exclusion, where CD8+ T cells are in surrounding stromal tissue but not within itself. To better identify patients with an immune-excluded phenotype, we developed two machine learning (ML) models quantify cell positivity and classify immunophenotype histological cancer specimen.
Biotinidase deficiency is inherited as an autosomal recessive trait that, unless treated with pharmacologic doses of biotin, can result in neurologic and cutaneous symptoms. We have identified two new mutations exon D the biotinidase gene children profound ascertained by newborn screening. Transition 511G→A near 5′ end results a substitution threonine for alanine171 (A171T) transversion 1330G→C occurs close to 3′ causing histidine aspartic acid 444 (D444H). The D444H mutation was detected...