A5034845140- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Lysosomal Storage Disorders Research
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- RNA regulation and disease
- Botulinum Toxin and Related Neurological Disorders
- Mitochondrial Function and Pathology
- Autism Spectrum Disorder Research
- Cellular transport and secretion
- Transcranial Magnetic Stimulation Studies
- Genetics and Neurodevelopmental Disorders
- Muscle activation and electromyography studies
- Genomic variations and chromosomal abnormalities
- DNA Repair Mechanisms
- Ginkgo biloba and Cashew Applications
- Balance, Gait, and Falls Prevention
- Cerebral Palsy and Movement Disorders
- EEG and Brain-Computer Interfaces
- Genomics and Rare Diseases
- Nuclear Receptors and Signaling
- Restless Legs Syndrome Research
- Dementia and Cognitive Impairment Research
- Multisensory perception and integration
- LGBTQ Health, Identity, and Policy
Sheba Medical Center
2016-2025
Tel Aviv University
2016-2025
Academic College of Tel Aviv-Yafo
2025
Genomics England
2021
University of Chicago
2020
Harvard University
2020
University of California, Los Angeles
2018-2020
The University of Melbourne
2020
Murdoch Children's Research Institute
2020
Brigham and Women's Hospital
2020
Parkinson's disease is a genetically complex disorder. Multiple genes have been shown to contribute the risk of disease, and currently 90 independent variants identified by genome-wide association studies. Thus far, number (including SNCA, LRRK2, GBA) contain variability across spectrum frequency effect, from rare, highly penetrant common alleles with small effect sizes. Variants in GBA, encoding enzyme glucocerebrosidase, are associated Lewy body diseases such as dementia. These variants,...
We conducted a double-blind, placebo-controlled study of 40 patients (aged 19 to 60 years) with clinical definite relapsing remitting (RR) MS and brain MRI confirmed. Patients were randomly assigned receive loading dose immunoglobulin IgG (0.4 g/kg/body weight per day for 5 consecutive days), followed by single booster doses weight) or placebo once every 2 months years. The primary outcome measures change in the yearly exacerbation rate (YER), proportion exacerbation-free patients, time...
Objective To present the long-term neurological outcome of Jewish Israeli patients with cerebrotendinous xanthomatosis (CTX) after several years chenodeoxycholic acid (CDCA) treatment. Methods A cross sectional observational study all a diagnosis CTX followed in referral outpatient clinic during 2003–2012. Results Eighteen (10 men) from 11 families were enrolled. Sixteen included analysis (2 had low compliance for treatment). The mean ± SD age at last evaluation was 35.0 9.2 (range, 16–45...
Abstract Background SMPD1 (acid‐sphingomyelinase) variants have been associated with Parkinson's disease in recent studies. The objective of this study was to further investigate the role mutations PD. Methods sequenced 3 cohorts (Israel Ashkenazi Jewish cohort, Montreal/Montpellier, and New York), including 1592 PD patients 975 controls. Additional data were available for 10,709 Acid‐sphingomyelinase activity measured by a mass spectrometry‐based assay York cohort. α‐Synuclein levels vitro...
The TMEM175/GAK/DGKQ locus is the 3rd strongest risk in genome-wide association studies of Parkinson disease (PD). We aimed to identify specific disease-associated variants this locus, and their potential implications.Full sequencing followed by genotyping associated was performed PD (n = 1,575) rapid eye movement sleep behavior disorder (RBD) patients 533) controls 1,583). Adjusted regression models a meta-analysis were performed. Association between glucocerebrosidase (GCase) activity...
Patients with Parkinson disease (PD) who harbor LRRK2 G2019S mutations may have increased risks of nonskin cancers. However, the results been inconsistent across studies.To analyze pooled data from 5 centers to further examine association between mutation and cancer among patients PD explore factors that could explain discrepancies.Clinical, demographic, genotyping as well outcomes were 1549 recruited movement disorders clinics located in Europe, Israel, United States. Associations examined...
<h3>Importance</h3> Pathogenic variants in<i>LRRK2</i>are a relatively common genetic cause of Parkinson disease (PD). Currently, the molecular mechanism underlying is unknown, and gain loss function (LOF) models pathogenesis have been postulated.<i>LRRK2</i>variants are reported to result in enhanced phosphorylation substrates increased cell death. However, double knockout of<i>Lrrk2</i>and its homologue<i>Lrrk1</i>results neurodegeneration mouse model, suggesting that may occur by LOF....
Genetic ataxias are associated with mutations in hundreds of genes high phenotypic overlap complicating the clinical diagnosis. Whole-exome sequencing (WES) has increased overall diagnostic rate considerably. However, upper limit this method remains ill-defined, hindering efforts to address remaining gap. To further assess role rare coding variation ataxic disorders, we reanalyzed our previously published exome cohort 76 predominantly adult and sporadic-onset patients, expanded total number...
Objective Creative thinking requires a combination of originality, flexibility, and usefulness. Several reports described enhanced artistic creativity in Parkinson disease (PD) patients treated with dopaminergic agents. We aimed to examine PD patients' ability perform tasks compared healthy controls verify whether is related an impulse control disorder (ICD) as complication therapy. Methods Right‐handed dopamine agonists and/or levodopa, age‐ education‐ matched neurologically were assessed...
Abstract Movement deterioration is the hallmark of Parkinson’s disease (PD), characterized by levodopa-induced motor-fluctuations (i.e., symptoms’ variability related to medication cycle) in advanced stages. However, motor symptoms are typically too sporadically and/or subjectively assessed, ultimately preventing effective monitoring their progression, and thus leading suboptimal treatment/therapeutic choices. Smartwatches (SW) enable a quantitative-oriented approach motor-symptoms...
In view of the fact that cancer patterns in patients with Parkinson disease (PD) differ from general population, we aimed to verify whether PD LRRK2 mutations have an increased risk for particular types.In this cross-sectional study, eligible consenting Jewish were genotyped predominant G2019S mutation. Oncologic data obtained by personal interview and reviewing patients' files. Stepwise logistic regression was applied model probability occurrence carriers vs noncarriers.Overall, 79/490...
Stimulation settings of deep brain stimulation (DBS) have evolved empirically within a limited parameter space dictated by first generation devices. There is need for controlled clinical studies, which evaluate efficacy and safety established programming practice against novel options provided modern neurostimulation devices.Here, we tested polarity reversal from conventional monopolar cathodic to anodic in an acute double-blind, randomized, cross-over study patients with PD implanted...
Friedreich ataxia is an inherited disorder characterized by degeneration of the peripheral and central nervous system hypertrophic cardiomyopathy. Homozygous mutations in frataxine (FXN) gene reduce expression frataxin cause accumulation iron mitochondria. Deferiprone, oral chelator, has been shown effective cell animal models ataxia. The results a 6-month randomized, double blind placebo-controlled study suggested that deferiprone 20 mg/kg/day may disease progression. authors present their...
We evaluated the prevalence of pathogenic repeat expansions in replication factor C subunit 1 (RFC1) and disabled adaptor protein (DAB1) an undiagnosed ataxia cohort from North America.A 596 predominantly adult-onset patients with familial or sporadic cerebellar was at a tertiary referral center excluded for common genetic causes ataxia. Patients were then screened presence RFC1 (AAGGG) DAB1 (ATTTC) using fluorescent repeat-primed PCR (RP-PCR). Two additional cohorts different centers,...
Biallelic PRKN mutation carriers with Parkinson's disease (PD) typically have an earlier onset, slow progression, and, often, different neuropathology compared to sporadic PD patients. However, the role of heterozygous variants in risk is controversial.Our aim was examine association between variants, including single-nucleotide and copy-number variations (CNVs), PD.We fully sequenced 2809 patients 3629 healthy controls, 1965 late-onset (63.97 ± 7.79 years, 63% men) 553 early-onset (43.33...
Genome-wide association studies (GWAS) have identified numerous loci associated with Parkinson's disease. The specific genes and variants that drive the associations within vast majority of these are unknown. We aimed to perform a comprehensive analysis selected determine potential role rare common genetic loci. fully sequenced 32 from 25 previously disease in 2657 patients 3647 controls three cohorts. Capture was done using molecular inversion probes targeting exons, exon-intron boundaries...
Freezing of gait (FoG) is a debilitating symptom advanced Parkinson's disease (PD) characterized by sudden, episodic stepping arrest despite the intention to continue walking. The etiology FoG still unknown, but accumulating evidence unraveled physiological signatures autonomic nervous system (ANS) around episodes. Here we aim investigate for first time whether detecting predisposition upcoming events from ANS activity measured at rest possible.We recorded heart-rate 1-min while standing in...
<b>Objectives: </b> To study the frequency of different gene mutations in patients with early-onset parkinsonism and bilateral subthalamic nucleus deep brain stimulation (STN-DBS) short- long-term surgical outcome mutation-positive (MUT+) -negative (MUT−) patients. <b>Methods: Eighty disease onset at age ≤ 45 years STN-DBS were screened for <i>Parkin</i> <i>PINK1</i> recurrent p.G2019S mutation <i>LRRK2</i> gene. The Unified Parkinson’s Disease Rating Scale (UPDRS) Hoehn Yahr (H-Y) scale...
Autosomal-recessive early-onset Parkinsonism (AREP) due to PINK1 mutations is characterized by an early-onset, slowly progressive disease, with a good response levodopa. Psychiatric and cognitive disturbances associated AREP have rarely been reported in the literature. We describe 2 brothers from Jewish-Iraqi consanguineous family homozygous nonsense mutation. Both patients presented anxiety dysphoria accompanied gait disturbance that developed subsequently into clinical depression. During...