A5048197676- Hereditary Neurological Disorders
- Genetic Neurodegenerative Diseases
- RNA Research and Splicing
- Cellular Mechanics and Interactions
- RNA regulation and disease
- Muscle Physiology and Disorders
- Congenital heart defects research
- Bone health and osteoporosis research
- COVID-19 and Mental Health
- Genomic variations and chromosomal abnormalities
- Neurogenetic and Muscular Disorders Research
- Thyroid Disorders and Treatments
- Parkinson's Disease Mechanisms and Treatments
- Genetics and Neurodevelopmental Disorders
- Cardiomyopathy and Myosin Studies
- Fungal and yeast genetics research
- Vitamin D Research Studies
- Signaling Pathways in Disease
- Long-Term Effects of COVID-19
- LGBTQ Health, Identity, and Policy
- Hormonal and reproductive studies
- Health and Lifestyle Studies
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Urban Planning and Valuation
Massachusetts General Hospital
2018-2024
Centro Neurolesi Bonino Pulejo
2020-2024
Harvard University
2018-2023
Istituti di Ricovero e Cura a Carattere Scientifico
2023
Arcadis (Czechia)
2021
University of Messina
2019
Center for Human Genetics
2016
University of Modena and Reggio Emilia
2008-2013
University of Massachusetts Chan Medical School
2013
Abstract Huntington’s disease (HD) is a dominant neurological disorder caused by an expanded HTT exon 1 CAG repeat that lengthens huntingtin’s polyglutamine tract. Lowering mutant huntingtin has been proposed for treating HD, but genetic modifiers implicate somatic expansion as the driver of onset. We find branaplam and risdiplam, small molecule splice modulators lower promoting pseudoexon inclusion, also decrease unstable in engineered cell model. Targeted CRISPR-Cas9 editing shows this...
Pre-mRNA splicing is a key controller of human gene expression. Disturbances in due to mutation lead dysregulated protein expression and contribute substantial fraction disease. Several classes modulator compounds (SMCs) have been recently identified establish that pre-mRNA represents target for therapy. We describe herein the identification BPN-15477, SMC restores correct ELP1 exon 20. Using transcriptome sequencing from treated fibroblast cells machine learning approach, we identify...
Familial dysautonomia (FD) is an autosomal recessive neurodegenerative disease that affects the development and survival of sensory autonomic neurons. FD caused by mRNA splicing mutation in intron 20 IKBKAP gene results a tissue-specific skipping exon corresponding reduction inhibitor kappaB kinase complex-associated protein (IKAP), also known as Elongator complex 1. To date, several promising therapeutic candidates for have been identified target underlying defect, increase functional IKAP...
Familial dysautonomia (FD) is a rare neurodegenerative disease caused by splicing mutation in elongator acetyltransferase complex subunit 1 (ELP1). This leads to the skipping of exon 20 and tissue-specific reduction ELP1, mainly central peripheral nervous systems. FD neurological disorder accompanied severe gait ataxia retinal degeneration. There currently no effective treatment restore ELP1 production individuals with FD, ultimately fatal. After identifying kinetin as small molecule able...
Abstract Background Osteoporosis is a common concern in the elderly that leads to fragile bones. Calcium supplementation plays crucial role improving bone health, reducing fracture risk, and supporting overall skeletal strength this vulnerable population. However, there conflicting evidence on safety of calcium supplements individuals. Aim The aim study was evaluate adherence, tolerability citrate osteopenic subjects. Methods In non-interventional, prospective, multicenter study, subjects...
Familial dysautonomia (FD) is an autonomic and sensory neuropathy caused by a mutation in the splice donor site of intron 20 ELP1 gene. Variable skipping exon leads to tissue-specific reduction level protein. We have shown that plant cytokinin kinetin able increase cellular protein levels vivo vitro through correction splicing. Studies FD patients determined not practical therapy due low potency rapid elimination. To identify molecules with improved efficacy, we developed cell-based...
Abstract Post-Stroke depression affects between 12% and 72% of patients who have suffered a stroke. The association low serum levels 25-hydroxyvitamin D (25(OH) D) increased risk is reported in both stroke non-stroke patients. Similarly, high 25(OH) might be associated with greater functional improvement during rehabilitation program. We wanted to investigate the effects an intensive on poststroke outcomes. wondered if daily motor cognitive functions could also effect mood abilities addition...
Facioscapulohumeral muscular dystrophy (FSHD), a common hereditary myopathy, is characterized by atrophy and weakness of selective muscle groups. FSHD considered an autosomal dominant disease with incomplete penetrance unpredictable variability clinical expression within families. Mice overexpressing FRG1 (FSHD region gene 1), candidate for this disease, develop progressive myopathy features the human disorder. Here, we show that in FRG1-overexpressing mice, fast muscles, which are most...
Background and Objectives: Osteoporosis is a metabolic skeletal disease resulting in low bone mass with increased fragility susceptibility to fractures. May lead rapid loss of mineral density (BMD) due physical inactivity reduced muscle contractions. Generally, the diagnosis osteoporosis made using dual X-ray absorptiometry (DXA), by measuring BMD trabecular score (TBS), which can be useful for detecting Therefore, aim this study was investigate, TBS, health status sample amyotrophic lateral...
Familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy, is caused by mutation in the Elongator complex protein 1 (ELP1) gene that leads to tissue-specific reduction of ELP1 protein. Our work generate phenotypic mouse model for FD headed discovery homozygous deletion Elp1 embryonic lethality prior mid-gestation. Given reduction, not loss, ELP1, we generated two new models introducing different copy numbers human transgene into knockout (Elp1−/−) observed expression rescues...
Background and Objectives: Normal human sexual functioning is a complex integration of an intact neuroanatomic substrate, vascular supply, balanced hormonal profile, predominance excitatory over inhibitory psychological mechanisms. However, in Parkinson’s disease (PD) often overlooked clinical practice, especially female patients. Materials Methods: In this cross-sectional study, we have investigated the frequency dysfunction possible correlation with psycho-endocrinological factors sample...
SUMMARY Recurrent deletion and duplication of ∼743 kilobases unique genomic sequence segmental duplications at chromosome 16p11.2 underlie a reciprocal disorder (RGD; OMIM 611913 614671) associated with neurodevelopmental psychiatric phenotypes, including intellectual disability, autism spectrum (ASD), schizophrenia (SCZ). To define molecular alterations the RGD, we performed transcriptome analyses mice copy number variants (CNVs) syntenic 7qF3 region human neuronal models derived from...
Abstract Pre-mRNA splicing is a key control point in human gene expression. Disturbances due to mutation or aberrant regulatory networks lead dysregulated protein expression and contribute substantial fraction of disease. Several classes active selective modulator compounds have been recently identified, thus proving that pre-mRNA viable target for therapy. We describe herein the identification BPN-15477, novel compound, restores correct exon 20 Elongator complex 1 (ELP1) carrying major...
Abstract Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder whose motor, cognitive, and behavioral manifestations are caused by an expanded, somatically unstable CAG repeat in the first exon of HTT that lengthens polyglutamine tract huntingtin. Genome-wide association studies (GWAS) have revealed DNA repair genes influence age-at-onset HD implicate somatic expansion as primary driver timing. To prevent consequent neuronal damage, small molecule splice modulators...
Abstract Familial dysautonomia (FD) is a fatal inherited congenital neuropathy characterized by both progressive neurological symptoms and systemic abnormalities, patients have reduced life expectancy. FD caused T-to-C mutation in intron 20 of the Elongator acetyltransferase complex subunit 1 ( ELP1 ) gene, which affects splicing process causing tissue-specific skipping exon 20. Here, we developed CRISPR base editor (BE) approach capable precisely correct this mutation. Using Cas9 variants...
In March 2020 the World Health Organization declared “pandemic state” due to COVID-19 imposing strict confinement of world population. People were forced spend more time at home, changing some daily routines, including social interactions, possibility perform sports, and diet habits. These changes could exert a greater impact on patients suffering from chronic diseases, such as endocrine patients. This study aimed assess effects Covid-19 induced quarantine habits in group...