A5028779483- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Glycogen Storage Diseases and Myoclonus
- Calcium signaling and nucleotide metabolism
- Retinal Development and Disorders
- Neuroscience and Neuropharmacology Research
- Carbohydrate Chemistry and Synthesis
- Trypanosoma species research and implications
- CRISPR and Genetic Engineering
- Protease and Inhibitor Mechanisms
- Bone and Dental Protein Studies
- Mosquito-borne diseases and control
- Lipid Membrane Structure and Behavior
- RNA regulation and disease
- Virus-based gene therapy research
- Neurogenetic and Muscular Disorders Research
- Connective tissue disorders research
- Ion channel regulation and function
- Adenosine and Purinergic Signaling
- Endoplasmic Reticulum Stress and Disease
- Child Nutrition and Feeding Issues
- Protein Kinase Regulation and GTPase Signaling
- Microtubule and mitosis dynamics
- Neonatal Health and Biochemistry
- Axon Guidance and Neuronal Signaling
Amicus Therapeutics (United States)
2021-2025
Amicus Therapeutics (United Kingdom)
2025
University of South Dakota
2015-2023
Sanford Research
2015-2023
CLN8 disease is a rare form of neuronal ceroid lipofuscinosis caused by biallelic mutations in the gene, which encodes transmembrane endoplasmic reticulum protein involved trafficking lysosomal enzymes. patients present with myoclonus, tonic-clonic seizures, and progressive declines cognitive motor function, many cases resulting premature death early life. There are currently no treatments that can cure or substantially slow progression. Using mouse model disease, we tested safety efficacy...
CLN3 disease, caused by biallelic mutations in the gene, is a rare pediatric neurodegenerative disease that has no cure or modifying treatment. The development of effective treatments been hindered lack etiological knowledge, but gene replacement emerged as promising therapeutic platform for such disorders. Here, we utilize mouse model to test safety and efficacy cerebrospinal fluid-delivered AAV9 therapy with study design optimized translatability. In this model, postnatal day one...
ABSTRACT Mouse models of CLN3 Batten disease, a rare lysosomal storage disorder with no cure, have improved our understanding biology and therapeutics through their ease use consistent display cellular pathology. However, the translatability murine is limited by disparities in anatomy, body size, life span inconsistent subtle behavior deficits that can be difficult to detect mutant mouse models, thereby limiting preclinical studies. Here, we present longitudinal characterization novel...
Batten disease is a family of rare, fatal, neuropediatric diseases presenting with memory/learning decline, blindness, and loss motor function. Recently, we reported the use an AAV9-mediated gene therapy that prevents progression in mouse model CLN6-Batten (Cln6nclf), restoring lifespans treated animals. Despite success our viral-mediated therapy, dosing strategy was optimized for delivery to brain parenchyma may limit therapeutic potential other disease-relevant tissues, such as eye. Here,...
Abstract SEC24 is mainly involved in cargo sorting during COPII vesicle assembly. There are four paralogs (A–D) vertebrates, which classified into two subgroups (SEC24A/B and SEC24C/D). Pathological mutations SEC24D cause osteogenesis imperfecta with craniofacial dysplasia humans. sec24d mutant fish also recapitulate the phenotypes. Consistent skeletal phenotypes, secretion of collagen was severely defective fish, emphasizing importance secretion. However, patient‐derived fibroblasts show...
CLN3 Batten disease is a rare pediatric neurodegenerative lysosomal disorder caused by biallelic disease-associated variants in CLN3. Despite decades of intense research, specific biofluid biomarkers status have not been reported, hindering clinical development therapies. Thus, we sought to determine whether individuals with elevated levels metabolites blood.We performed an exhaustive metabolomic screen using serum samples from novel minipig model and validated findings pig CSF Cln3 mouse...
Commonly known as Batten disease, the neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of rare pediatric lysosomal storage disorders characterized by intracellular accumulation autofluorescent material (known lipofuscin), progressive neurodegeneration, and neurological symptoms. In 2002, disease-causing NCL mutation in CLN6 gene was identified (c.214G > T) Costa Rican population, but frequency this among local disease patients remains incompletely characterized, do...
Abstract Through the process of neuronal differentiation, newly born neurons change from simple, spherical cells to complex, sprawling with many highly branched processes. One first stages in this is neurite initiation, wherein cytoskeletal modifications facilitate membrane protrusion and extension cell body. Hundreds actin modulators microtubule-binding proteins are known be involved process, but relatively little about how upstream regulators bring these complex networks together at...
Acid alpha-glucosidase (GAA) is a lysosomal glycogen-catabolizing enzyme, the deficiency of which leads to Pompe disease. disease can be treated with systemic recombinant human GAA (rhGAA) enzyme replacement therapy (ERT), but current standard care exhibits poor uptake in skeletal muscles, limiting its clinical efficacy. Furthermore, it unclear how specific cellular processing steps after delivery lysosomes impact undergoes both proteolytic cleavage and glycan trimming within endolysosomal...
Abstract Background CLN3 disease (also known as Batten or Juvenile Neuronal Ceroid Lipofuscinosis) is a rare pediatric neurodegenerative disorder caused by biallelic mutations in . While extensive efforts have been undertaken to understand etiology, pathology, and clinical progression, little about the impact of on parents caregivers. Here, we investigated care, family experiences using semi-structured interviews with 39 individuals disease. Analysis included response categorization...
Batten disease is unique among lysosomal storage disorders for the early and profound manifestation in central nervous system, but little known regarding potential neuron-specific roles disease-associated proteins. We demonstrate substantial overlap protein interactomes of three transmembrane proteins (CLN3, CLN6, CLN8), that their absence leads to synaptic depletion key partners (i.e., SNAREs tethers) altered SNARE complexing vivo , demonstrating a novel shared etiology.