A5058559931- Lysosomal Storage Disorders Research
- Glycogen Storage Diseases and Myoclonus
- Virus-based gene therapy research
- Cellular transport and secretion
- Viral Infections and Vectors
- Viral Infectious Diseases and Gene Expression in Insects
- Herpesvirus Infections and Treatments
- Mosquito-borne diseases and control
- Vector-Borne Animal Diseases
- RNA Interference and Gene Delivery
- Calcium signaling and nucleotide metabolism
- Immune Cell Function and Interaction
- Biochemical and Molecular Research
- CRISPR and Genetic Engineering
- Trypanosoma species research and implications
- Immune Response and Inflammation
- Insect symbiosis and bacterial influences
- Biomedical and Chemical Research
- Advanced biosensing and bioanalysis techniques
- Ginkgo biloba and Cashew Applications
- Genomics and Rare Diseases
- Poxvirus research and outbreaks
- Plant Virus Research Studies
- Neonatal Respiratory Health Research
- Macrophage Migration Inhibitory Factor
BioMarin (United States)
2016-2020
Universität Hamburg
2017
University Medical Center Hamburg-Eppendorf
2017
Klinik für Frauenheilkunde
2011
Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
2011
University of Portland
2011
Oregon Health & Science University
2011
Ludwig-Maximilians-Universität München
2011
Harvard University
1995-2000
Massachusetts General Hospital
1995-2000
Recombinant human tripeptidyl peptidase 1 (cerliponase alfa) is an enzyme-replacement therapy that has been developed to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare lysosomal disorder causes progressive dementia in children.
Novel hybrid vectors, which incorporate critical elements of both herpes simplex virus type 1 (HSV-1) amplicon vectors and adeno-associated (AAV) are able to sustain transgene expression in dividing glioma cells for over 2 weeks. These combine the high infectibility large capacity HSV-1 with potential episomal amplification chromosomal integration AAV vectors. The contain origin DNA replication, oriS, cleavage/packaging signal, pac, allow replication packaging virions. lacZ reporter gene...
Rare or orphan diseases often are inherited and overwhelmingly affect children. Many of these have no treatments, incurable, a devastating impact on patients their families. Regulatory standards for drug approval rare must ensure that receive safe efficacious treatments. However, regulatory bodies shown flexibility in applying to development diseases, given the unique challenges hinder efficient effective traditional clinical trials, including low patient numbers, limited understanding...
Lymphocytes taken from the cord blood of newborns have active suppressor activity. Using in vitro PWM-stimulated cocultures, unfractionated T cells potently suppressed expected immunoglobulin G (IgG) synthesis their mothers' peripheral lymphocytes (PBL). positive and negative selection techniques, we characterized cell as expressing OKT4+T8- phenotype. This lymphocyte subset maternal IgG after depletion cells, implicating ability newborn to suppress directly rather than by inducing adult...
Neuronal ceroid lipofuscinosis type-2 (CLN2) disease is a rare, autosomal recessive, pediatric-onset, neurodegenerative lysosomal storage caused by mutations in the TPP1 gene. Cerliponase alfa (Brineura®), recombinant form of human tripeptidyl peptidase-1, was recently developed as treatment for CLN2 disease. In clinical trials, primary end point to evaluate effect aggregate score motor and language (ML) domains Clinical Rating Scale, an adaptation Hamburg scale's component items that...
SUMMARY Reassortant bunyaviruses derived from two members of the California serogroup (La Crosse/original and Tahyna/181-57) viruses were used to demonstrate that large M r viral protein (L) is encoded by L RNA segment. Radiolabelled proteins analysed discontinuous SDS–PAGE. The La Crosse virus was observed migrate ahead its Tahyna counterpart when electrophoresed through a 5% acrylamide resolving gel. Among reassortant viruses, phenotype segregated with After confirming genotype in this...
Abstract Objective Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare, progressive, fatal neurodegenerative pediatric disorder resulting from deficiencies of the lysosomal enzyme tripeptidyl peptidase 1 that are caused by mutations in TPP1 . Identifying biomarkers CLN2 disease progression will be important assessing efficacy therapeutic interventions for this disorder. Neurofilament light an intrinsic component healthy neurons; elevated circulating extracellular neurofilament...
Background: CLN2 disease is an autosomal recessively inherited storage disorder caused by deficient activity of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1). The late infantile phenotype characterized rapid psychomotor decline and epilepsy. Early diagnosis exact knowledge natural clinical course are important for evaluating experimental therapies.
To study the expression of La Crosse virus (LAC) glycaproteins, G1 and G2, we constructed a cDNA copy open reading frame (ORF) middle RNA segment expressed it in recombinant vaccinia (VV.ORF). Cells infected with W.ORF G2 at cell surface formed syncytia pH profile similar to that LAC. These experiments provide system studying biological functions LAC glycoproteins, including processing, targeting, fusion, receptor binding, antigenicity.
A number of virus vectors have been developed for gene delivery to the nervous system. Virus still provide most efficient means delivery, and this is critical as only a small volume inoculum can be used without damaging neurons. Each four types currently in use their advantages disadvantages. Highest titers achieved with herpes adenovirus vectors, retrovirus adeno-associated (AAV) yielding lower titers. The transgene capacity each from highest lowest is: (30 kb), (8-10 (7-8 kb) AAV (4.5 kb)....
Background: CLN2 disease, a rare, inherited, pediatric, neurodegenerative lysosomal storage disorder caused by TPP1 deficiency, is characterized seizures, language and motor function loss, blindness, early death. An open-label study demonstrated that intracerebroventricular (ICV) infusion of 300 mg cerliponase alfa, recombinant human enzyme, every other week for 48 weeks slowed deterioration in function. This extension (NCT02485899) assesses the long-term safety efficacy alfa up to 240 weeks.
Cerliponase alfa is recombinant human tripeptidyl peptidase 1 (TPP1) delivered by i.c.v. infusion for CLN2, a pediatric neurodegenerative disease caused deficiency in lysosomal enzyme TPP1. We report the pharmacokinetics (PK) and pharmacodynamics of cerliponase alfa, first replacement therapy, characterized phase I/II study. Escalating doses (30-300 mg Q2W) followed 300 Q2W ≥ 48 weeks were administered 24 patients aged 3 years. Concentrations peaked cerebrospinal fluid (CSF) at end ~ 4-hour...
Background: CLN2 disease, a rare, inherited, pediatric-onset, neurodegenerative lysosomal storage disorder caused by TPP1 enzyme deficiency, is characterized seizures, ataxia, rapid loss of language and motor functions, blindness, early death. Cerliponase alfa (BMN 190) recombinant human enzyme. This phase 1/2, multicenter, open-label, dose-escalation study evaluated the safety, tolerability, efficacy every other week intracerebroventricular (ICV) infusions cerliponase in children with aged...