A5069764549- Lysosomal Storage Disorders Research
- Glycogen Storage Diseases and Myoclonus
- Obsessive-Compulsive Spectrum Disorders
- Autism Spectrum Disorder Research
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Child and Adolescent Psychosocial and Emotional Development
- Eating Disorders and Behaviors
- Trypanosoma species research and implications
- Cellular transport and secretion
- Neurogenetic and Muscular Disorders Research
- Cystic Fibrosis Research Advances
- Attention Deficit Hyperactivity Disorder
- Adolescent and Pediatric Healthcare
- Health Systems, Economic Evaluations, Quality of Life
- Glycosylation and Glycoproteins Research
- Genetic Neurodegenerative Diseases
- Behavioral and Psychological Studies
- Chronic Lymphocytic Leukemia Research
- Autoimmune and Inflammatory Disorders Research
- CRISPR and Genetic Engineering
- Health and Medical Research Impacts
- Childhood Cancer Survivors' Quality of Life
Kennedy Krieger Institute
2021-2025
Johns Hopkins University
2022-2024
University of Rochester
2013-2024
McGill University
2024
Johns Hopkins Medicine
2023-2024
University of South Florida
2024
Pennsylvania State University
2024
University of Pennsylvania
2022-2024
University of Rochester Medical Center
2014-2023
Boston University
2022
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...
The neuronal ceroid lipofuscinoses constitute one of many groups rare childhood diseases for which disease-modifying treatments are nonexistent. Disease-specific barriers to therapeutic success include incomplete understanding disease pathophysiology and limitations that cannot adequately cross the blood-brain barrier access central nervous system. Therapeutic development in shares challenges with other diseases, such as natural history inform trial design, need alternatives randomized...
Introduction To improve our understanding of sex differences in the clinical characteristics Parkinson's Disease, we sought to examine features and disease severity men women with early treated Disease (PD) enrolled a large-scale trial. Methods Analysis was performed baseline data from National Institutes Health Exploratory Trials (NET-PD) Long-term Study-1, randomized, multi-center, double-blind, placebo-controlled study 10 grams oral creatine/day individuals early, PD. We compared mean age...
<h3>Objective:</h3> The primary objective of this research was to characterize the movement disorders associated with <i>FOXG1</i> mutations. <h3>Methods:</h3> We identified patients mutations who were referred either a tertiary disorder clinic or epilepsy service and retrospectively reviewed medical records, clinical investigations, neuroimaging, available video footage. administered telephone-based questionnaire regarding functional impact perceived efficacy treatment caregivers one cohort...
We interrogated auditory sensory memory capabilities in individuals with CLN3 disease (juvenile neuronal ceroid lipofuscinosis), specifically for the feature of "duration" processing. Given decrements processing abilities associated later-stage disease, we hypothesized that duration-evoked mismatch negativity (MMN) event related potential (ERP) would be a marker progressively atypical cortical this population, applicability as brain-based biomarker clinical trials. employed three stimulation...
Objective Despite evidence of elevated risk factors for suicidal thoughts and behavior in youth with Tourette syndrome chronic tic disorders (CTD), few studies have actually examined that relationship. This study documented the frequency clinical correlates behaviors a sample children adolescents CTD (N = 196, range 6–18 years old). The content is solely responsibility authors does not necessarily represent official views Centers Disease Control. Method Youth parents completed battery...
Abstract Genomic and gene‐targeted therapies hold great promise in addressing the global issue of rare diseases. To achieve this promise, however, it is critical twin goals equity access to testing diagnosis, therapy be considered early life cycle development implementation. Rare disease researchers clinicians must simultaneously recognize life‐altering potential diagnosis administration therapeutics while acknowledging that not everyone who experiences a needs these will able afford or...
To use the Unified Batten Disease Rating Scale (UBDRS) to measure rate of decline in physical and functional capability domains patients with juvenile neuronal ceroid lipofuscinosis (JNCL) or disease, a neurodegenerative lysosomal storage disorder. We have evaluated UBDRS subjects JNCL since 2002; during that time, scale has been refined improve reliability validity. Now therapies are being proposed prevent, slow, reverse course JNCL, will play an important role quantitatively assessing...
Abstract Mutations in CLN3 lead to photoreceptor cell loss disease, a lysosomal storage disorder characterized by childhood-onset vision loss, neurological impairment, and premature death. However, how mutations cause death is not known. Here, we show that required for phagocytosis of outer segment (POS) retinal pigment epithelium (RPE) cells, cellular process essential survival. Specifically, proportion human, mouse, iPSC-RPE cells localized RPE microvilli, the site POS phagocytosis....
Background: The neuronal ceroid lipofuscinoses (Batten disease) are rare neurodegenerative lysosomal storage diseases principally of childhood onset and an autosomal recessive inheritance pattern. Cognitive regression is a hallmark the disease, has been characterized as part University Rochester Batten Center's prospective longitudinal natural history. objective present study was to establish convergent validity two most recent versions Wechsler Intelligence Scale for Children in this...
Mycophenolate, an immunosuppressant, is commonly used off-label for autoimmune neurological conditions. In CLN3 disease, a neurodegenerative disorder of childhood, preclinical and clinical data suggest secondary autoimmunity inflammation throughout the central nervous system are key components pathogenesis. We tested short-term tolerability mycophenolate in individuals with preparation possible long-term efficacy trials this drug. conducted randomized, double-blind, placebo-controlled,...
Abstract Recent advancements in gene‐targeted therapies have highlighted the critical role data sharing plays successful translational drug development for people with rare diseases. To scale these efforts, we need to systematize principles, creating opportunities more rapid, efficient, and scalable discovery/testing including long‐term transparent assessment of clinical safety efficacy. A number challenges will be addressed, logistical difficulties studying diseases affecting individuals...
ABSTRACT Background The risk for malignant melanoma is higher than expected in Parkinson's disease (PD). National Institutes of Health (NIH) Exploratory Trials PD (NET‐PD) Long‐term Study 1 (LS‐1) trial a contemporary phase 3 study subjects with early, treated PD. objective this work was to assess the incidence cohort. Methods Incident cases were identified from adverse events log. number calculated, using rates and person‐years. Results A total 618 females 1119 males followed 6452...
Abstract Most rare diseases are caused by single‐gene mutations, and as such, lend themselves to a host of new gene‐targeted therapies technologies including antisense oligonucleotides, phosphomorpholinos, small interfering RNAs, variety gene delivery editing systems. Early successes encouraging, however, given the substantial number distinct diseases, ability scale these will be unsustainable without development efficiencies. Herein, we discuss need for genomic newborn screening match pace...
Remote technology provides an opportunity to extend the reach of clinical care and research for pediatric rare disease. This pilot study evaluated feasibility reliability neuropsychological evaluation, using remote audiovisual technology, in assessment children with juvenile Batten Three disease 1 healthy sibling completed a standardized cognitive assessment. Results indicated high agreement between in-person evaluator when comparing subjects’ test scores. initial suggests it is feasible...
Aim To evaluate seizure phenomenology, treatment, and course in individuals with juvenile neuronal ceroid lipofuscinosis (JNCL). Method Data from an ongoing natural history study of JNCL were analyzed using cross‐sectional longitudinal methods. Seizures evaluated the Unified Batten Disease Rating Scale, a disease‐specific quantitative assessment tool. Results Eighty‐six children (44 males, 42 females) assessed at average three annual visits (range 1–11). percent ( n =74) experienced least...
CLN1 disease (neuronal ceroid lipofuscinosis type 1) is a rare, genetic, neurodegenerative lysosomal storage disorder caused by palmitoyl-protein thioesterase 1 (PPT1) enzyme deficiency. Clinical features include developmental delay, psychomotor regression, seizures, ataxia, movement disorders, visual impairment, and early death. In general, the later age at symptom onset, more protracted course. We sought to evaluate current evidence develop expert practice consensus support clinicians who...
Tics and tic disorders can significantly impact children, but limited screening tools diagnostic challenges may delay access to care. The current study attempted address these gaps by evaluating sensitivity specificity of the Motor or Vocal Inventory (MOVeIT), a symptom screener, Description Tic Symptoms (DoTS), brief assessment for disorders. Children (n = 100, age 6–17 years old) with attending Tourette specialty clinic community-recruited sample without tics completed gold-standard...