A5029896435- Parkinson's Disease Mechanisms and Treatments
- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Adenosine and Purinergic Signaling
- Carbohydrate Chemistry and Synthesis
- Trypanosoma species research and implications
- Neurogenetic and Muscular Disorders Research
- Exercise and Physiological Responses
- RNA modifications and cancer
- Autophagy in Disease and Therapy
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- Genetic Neurodegenerative Diseases
- Complement system in diseases
- Muscle Physiology and Disorders
- Nuclear Receptors and Signaling
- Alzheimer's disease research and treatments
- Adipose Tissue and Metabolism
- Nerve injury and regeneration
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- RNA regulation and disease
Northwestern University
2017-2024
University of Minnesota
2015
Genome sequencing is often pivotal in the diagnosis of rare diseases, but many these conditions lack specific treatments. We describe how molecular a rare, fatal neurodegenerative condition led to rational design, testing, and manufacture milasen, splice-modulating antisense oligonucleotide drug tailored particular patient. Proof-of-concept experiments cell lines from patient served as basis for launching an "N-of-1" study milasen within 1 year after first contact with There were no serious...
Parkinson disease (PD) is a neurodegenerative disorder characterized by the abnormal intracellular accumulation of SNCA/α-synuclein. While exact mechanisms underlying SNCA pathology are not fully understood, increasing evidence suggests involvement autophagy as well lysosomal deficiencies. Because CTSD (cathepsin D) has been proposed to be major protease involved in degradation, its deficiency linked presence insoluble conformers brain mice and humans transcellular transmission aggregates....
Neuronal ceroid lipofuscinosis type 7 (CLN7) disease is a lysosomal storage caused by mutations in the facilitator superfamily domain containing 8 (MFSD8) gene, which encodes membrane-bound protein, MFSD8. To test effectiveness and safety of adeno-associated viral (AAV) gene therapy, an vitro study demonstrated that AAV2/MFSD8 dose dependently rescued function fibroblasts from CLN7 patient. An vivo efficacy using intrathecal administration AAV9/MFSD8 to Mfsd8– /– mice at P7–P10 or P120 with...
Abstract Disrupted glucose metabolism and protein misfolding are key characteristics of age-related neurodegenerative disorders including Parkinson’s disease, however their mechanistic linkage is largely unexplored. The hexosamine biosynthetic pathway utilizes uridine-5’-triphosphate to generate N-linked glycans required for folding in the endoplasmic reticulum. Here we find that patient midbrain cultures accumulate uridine-5’-triphosphate, while N-glycan synthesis rates reduced. Impaired...
Duchenne muscular dystrophy (DMD), the most common and severe type of dystrophinopathy, is an X-linked recessive genetic disease caused by absence dystrophin, which leads to fragility vulnerability sarcolemma mechanical stretching with increased membrane permeability. Currently, glucocorticoids such as prednisolone are only medication available for DMD. However, molecular pathways responsible this effect still unclear. In addition, it remains unclear whether sex-related factors, including...