A5015256793- Calcium signaling and nucleotide metabolism
- Cellular transport and secretion
- Adenosine and Purinergic Signaling
- Nuclear Receptors and Signaling
- Lysosomal Storage Disorders Research
- Neurological diseases and metabolism
- Glycosylation and Glycoproteins Research
- RNA regulation and disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Signaling Pathways in Disease
- Electrochemical sensors and biosensors
- Immune cells in cancer
- Retinal Development and Disorders
- Metabolism and Genetic Disorders
- Prion Diseases and Protein Misfolding
Massachusetts General Hospital
2020-2025
Harvard University
2020-2025
Children's Hospital of Philadelphia
2025
Mucolipidosis IV (MLIV) is a rare, autosomal recessive, lysosomal disease characterized by intellectual disability, motor deficits, and progressive vision loss. Using adeno-associated vector 9 (AAV9) AAV-PHP.B as delivery vectors, we previously demonstrated the feasibility of modifying course in mouse model MLIV human MCOLN1 gene transfer. Here, using primate-enabling capsid AAV.CPP.16 (CPP16), constructed new, clinic-oriented expression its efficacy preclinical MLIV. Systemic administration...
Beta-propeller protein-associated neurodegeneration (BPAN) is an ultra-rare, X-linked dominant, neurodevelopmental, and neurodegenerative disease caused by loss-of-function mutations in the WDR45 gene. It manifests neurodevelopmental delay seizures followed secondary neurological decline with dystonia/parkinsonism dementia adolescence early adulthood characterized progressive accumulation of iron basal ganglia. encodes β-propeller-shaped scaffold protein, or WD repeat domain...
Mucolipidosis IV (MLIV) is an orphan disease leading to debilitating psychomotor deficits and vision loss. It caused by loss-of-function mutations in the MCOLN1 gene that encodes lysosomal transient receptor potential channel mucolipin1, or TRPML1. With no existing therapy, unmet need this very high. Here, we showed AAV-mediated CNS-targeted transfer of human rescued motor function alleviated brain pathology MLIV mouse model. Using AAV-PHP.b vector symptomatic mice, long-term reversal...
Mucolipidosis IV (MLIV) is an ultra-rare, recessively inherited lysosomal disorder resulting from inactivating mutations in MCOLN1, the gene encoding cation channel TRPML1. The disease primarily affects central nervous system (CNS) and manifests first year with cognitive motor developmental delay, followed by a gradual decline neurological function across second decade of life, blindness, premature death third or fourth decades. Brain pathology manifestations MLIV are consistent...
Abstract Mucolipidosis IV (MLIV, OMIM 252650) is an orphan disease leading to debilitating psychomotor deficits and vision loss. It caused by loss-of-function mutations in the MCOLN1 gene that encodes thethe lysosomal transient receptor potential channel mucolipin 1 (TRPML1). With no existing therapy, unmet need this very high. Here we show AAV-mediated transfer of human rescues motor function alleviates brain pathology Mcoln1 −/− MLIV mouse model. Using AAV-PHP.b vector for initial...
Abstract Beta-propeller protein-associated neurodegeneration (BPAN) is an ultra-rare, X-linked dominant, neurodegenerative disease caused by loss-of-function mutations in the WDR45 gene. It manifests neurodevelopmental delay and seizures followed secondary neurologic decline with dystonia/parkinsonism dementia adolescence early adulthood characterized progressive accumulation of iron basal ganglia. encodes β-propeller-shaped scaffold protein, or WIPI4, which plays important role...
Abstract Mucolipidosis IV (MLIV) is an autosomal-recessive pediatric disease that leads to motor and cognitive deficits loss of vision. It caused by the function lysosomal channel transient receptor potential mucolipin-1, TRPML1, associated with early brain phenotype consisting glial reactivity, hypomyelination, abnormalities, increased cytokine expression. Although field approaching first translationally relevant therapy, we currently lack a molecular signature can be used detect...
Abstract 1 Mucolipidosis IV (MLIV) is an ultra-rare, recessively inherited lysosomal disorder resulting from inactivating mutations in MCOLN1 , the gene encoding cation channel TRPML1. The disease primarily affects central nervous system (CNS) and manifests first year with cognitive motor developmental delay, followed by a gradual decline neurological function across second decade of life, blindness, premature death third or fourth decades. Brain pathology manifestations MLIV are consistent...
Abstract Mucolipidosis IV (MLIV) is a rare, autosomal recessive, lysosomal disease characterized by intellectual disability, motor deficits and progressive vision loss. Using AAV9 AAV-PHP.B as delivery vectors, we previously demonstrated the feasibility of modifying course in mouse model MLIV human MCOLN1 gene transfer. Here, using primate-enabling capsid AAV.CPP.16 (CPP16), constructed new, clinic-oriented expression vector its efficacy preclinical MLIV. Systemic administration CPP16- adult...