13 Works

The STARS phase 2 study: a randomized controlled trial of gaboxadol in Angelman syndrome

Lynne Bird, Cesar Ochoa-Lubinoff, Wen-Hann Tan, Gali Heimer, Raun Melmed, Amit Rakhit, Jeannie Visootsak, Matthew During, Rebecca Burdine, Christina Holcroft, Alexander Kolevzon & Ronald Thibert
Objective: To evaluate safety and tolerability and exploratory efficacy endpoints for gaboxadol (OV101) compared with placebo in individuals with Angelman syndrome (AS). Methods: Gaboxadol is a highly selective orthosteric agonist that activates γ-subunit–containing extrasynaptic γ-aminobutyric acid type A (GABAA) receptors. In a multicenter, double-blind, placebo-controlled, parallel-group trial, adolescent and adult individuals with a molecular diagnosis of AS were randomized (1:1:1) to 1 of 3 dosing regimens for a duration of 12 weeks: placebo morning dose...

Cerebrovascular disease progression in patients with ACTA2 Arg179 pathogenic variants supplementary materials

Arne Lauer, Samantha Speroni, Jay Patel, Ellen Regalado, Myoung Choi, Edward Smith, Jayashree Kalpathy-Kramer, Paul Caruso, Dianna Milewicz & Patricia Musolino
Our study entitled “Cerebrovascular disease progression in patients with ACTA2 Arg179 Pathogenic Variants” examines progression of imaging biomarkers of stroke, arterial steno-occlusive disease and white matter injury in patients with smooth muscle dysfunction syndrome caused by mutations in the ACTA2 gene (ACTA2 Arg179 pathogenic variants). We found characteristic patterns of acute white matter ischemic injury and progressive internal carotid artery stenosis on MRI. Longitudinal analysis showed both stable and progressive lesion entities. The data was...

Data from: In vivo human whole-brain Connectom diffusion MRI dataset at 760 µm isotropic resolution (PART II)

Fuyixue Wang, Zijing Dong, Qiyuan Tian, Congyu Liao, Qiuyun Fan, W. Scott Hoge, Boris Keil, Jonathan R. Polimeni, Lawrence L. Wald, Susie Y. Huang & Kawin Setsompop
This whole-brain in vivo diffusion MRI dataset was acquired at 760 µm isotropic resolution and sampled at 1260 q-space points across 9 two-hour sessions on a single healthy subject. It was acquired using state-of-the-art acquisition hardware and advanced reconstruction to achieve high SNR at such resolution, including a high-gradient-strength Connectom scanner, a custom-built 64-channel phased-array coil, a personalized motion-robust head stabilizer, a recently developed SNR-efficient dMRI acquisition, and parallel imaging reconstruction with advanced ghost reduction...

Data from: Developmental loss of neurofibromin across distributed neuronal circuits drives excessive grooming in Drosophila

Seth Tomchik, Lanikea King, Tamara Boto, Valentina Botero, Ari Aviles, Breanna Jomsky, Chevara Joseph & James Walker
Neurofibromatosis type 1 is a monogenetic disorder that predisposes individuals to tumor formation and cognitive and behavioral symptoms. The neuronal circuitry and developmental events underlying these neurological symptoms are unknown. To better understand how mutations of the underlying gene (NF1) drive behavioral alterations, we have examined grooming in the Drosophila neurofibromatosis 1 model. Mutations of the fly NF1 ortholog drive excessive grooming, and increased grooming was observed in adults when Nf1 was knocked down during...

Association of caffeine and related analytes with resistance to Parkinson’s disease among LRRK2 mutation carriers: a metabolomic study

Grace F Crotty, Romeo Maciuca, Eric A Macklin, Junhua Wang, Manuel Montalban, Sonnet S. Davis, Jamal I Alkabsh, Rachit Bakshi, Xiqun Chen, Alberto Ascherio, Giuseppe Astarita, Sarah Huntwork-Rodriguez & Michael A Schwarzschild
Objective: To identify markers of resistance to developing Parkinson’s disease (PD) among LRRK2 mutation (LRRK2+) carriers, we carried out metabolomic profiling in individuals with PD and unaffected controls (UC), with and without the LRRK2 mutation. Methods: Plasma from 368 PD and UC subjects in the LRRK2 Cohort Consortium (LCC), comprising 118 LRRK2+/PD+, 115 LRRK2+/UC, 70 LRRK2-/PD+ and 65 LRRK2-/UC, and CSF available from 68 of them were analyzed by liquid chromatography with mass spectrometry. For...

Ligand-dependent effects of methionine-8 oxidation in parathyroid hormone peptide analogs

Thomas Gardella, Vsevolod Katritch, Saheem Zaidi, Eileen Daley, Ashok Khatri & Jean-Pierre Vilardaga
LA-PTH is a long-acting parathyroid hormone (PTH) peptide analog in pre-clinical development for hypoparathyroidism (HP). Like native PTH, LA-PTH contains a methionine at position 8 that is predicted to be critical for function. We assessed the impact of methionine oxidation on the functional properties of LA-PTH and control PTH ligands. Oxidation of PTH(1-34) resulted in marked (~20-fold) reductions in binding affinity on the PTH receptor-1 (PTHR1) in cell membranes, similarly diminished potency for cAMP signaling...

Thalamic encoding of lexical status is lateralized during reading aloud

Dengyu Wang, Witold J. Lipski, Alan Bush, Anna Chrabaszcz, Christina Dastolfo-Hromack, Michael W. Dickey, Julie A. Fiez & R. Mark Richardson
To explore whether the thalamus participates in lexical status encoding, local field potentials were recorded in patients undergoing deep brain stimulation lead implantation while they read aloud single-syllable words and nonwords. Bilateral decreases in thalamic beta (12-30Hz) activity were preferentially locked to stimulus presentation, and these decreases were greater when nonwords were read. Increased broadband gamma (70-150Hz) activity also was locked preferentially to speech onset bilaterally, but greater nonword-related increases in this activity were observed...

Fine particulate matter and neuroanatomic risk for Alzheimer’s disease in older women

Diana Younan, Xinhui Wang, Ramon Casanova, Ryan Barnard, Sarah Gaussoin, Santiago Saldana, Andrew Petkus, Daniel Beavers, Susan Resnick, JoAnn Manson, Marc Serre, William Vizuete, Victor Henderson, Bonnie Sachs, Joel Salinas, Margaret Gatz, Mark Espeland, Helena Chui, Sally Shumaker, Stephen Rapp & Jiu-Chiuan Chen
Objective: To examine whether late-life exposure to PM2.5 (particulate matter with aerodynamic diameters <2.5-µm) contributes to progressive brain atrophy predictive of Alzheimer’s disease (AD) using a community-dwelling cohort of women (aged 71-89) with up to two brain MRI scans (MRI-1: 2005-6; MRI-2: 2010-11). Methods: AD pattern similarity (AD-PS) scores, developed by supervised machine learning and validated with MRI data from the AD Neuroimaging Initiative, was used to capture high-dimensional gray matter atrophy in brain areas...

Data from: Distinct epileptiform abnormalities are associated with clinical seizures in Alzheimer’s disease

Alice Lam, Rani Sarkis, Kyle R Pellerin, Jin Jing, Barbara A Dworetzky, Daniel B Hoch, Claire S Jacobs, Jong Woo Lee, Daniel S Weisholtz, Rodrigo Zepeda, M. Brandon Westover, Andrew J. Cole & Sydney S Cash
Objective: Examine the relationship between scalp EEG biomarkers of hyperexcitability in Alzheimer’s disease (AD) and determine how these electrical biomarkers relate to the clinical expression of seizures in AD. Methods: In this cross-sectional study, we performed 24-hour ambulatory scalp EEGs on 43 cognitively normal elderly healthy controls (HC), 41 early-stage AD participants with no history or risk factors for epilepsy (AD-NoEp), and 15 early-stage AD participants with late-onset epilepsy related to AD (AD-Ep). Two epileptologists,...

Data from: In vivo human whole-brain Connectom diffusion MRI dataset at 760 µm isotropic resolution (PART I)

Fuyixue Wang, Zijing Dong, Qiyuan Tian, Congyu Liao, Qiuyun Fan, W. Scott Hoge, Boris Keil, Jonathan R. Polimeni, Lawrence L. Wald, Susie Y. Huang & Kawin Setsompop
This whole-brain in vivo diffusion MRI dataset was acquired at 760 µm isotropic resolution and sampled at 1260 q-space points across 9 two-hour sessions on a single healthy subject. It was acquired using state-of-the-art acquisition hardware and advanced reconstruction to achieve high SNR at such resolution, including a high-gradient-strength Connectom scanner, a custom-built 64-channel phased-array coil, a personalized motion-robust head stabilizer, a recently developed SNR-efficient dMRI acquisition, and parallel imaging reconstruction with advanced ghost reduction...

RNAseq data from: A novel TNFR2 agonist antibody expands highly potent regulatory T cells

Willem Kuhtreiber
Patients suffering from inflammatory diseases may benefit by enhancing the function of immunosuppressive regulatory T cells (Tregs). Tumor necrosis factor receptor 2 (TNFR2) has emerged as a central control switch on Tregs for maintaining and restoring the immune balance. Here, we characterized a new human TNFR2-directed antibody agonist. We found that the antibody agonist expands Tregs with a cellular phenotype and mechanistic properties of maximally suppressive Tregs. RNA-sequencing and metabolite data showed that the antibody...

Neural signatures of alpha2 adrenergic agonist-induced unconsciousness and awakening by antagonist

Jesus J. Ballesteros, Jessica Briscoe & Yumiko Ishizawa
The dataset provides all necessary raw data to replicate the main analisys and figures in the manuscript.

Data from: Nonlinearities between inhibition and T-type calcium channel activity bidirectionally regulate thalamic oscillations

Adam Lu, Christine Lee, Max Kleiman-Weiner, Brian Truong, Megan Wang, John Huguenard & Mark Beenhakker
Absence seizures result from 3-5 Hz generalized thalamocortical oscillations that depend on highly regulated inhibitory neurotransmission in the thalamus. Efficient reuptake of the inhibitory neurotransmitter GABA is essential, and reuptake failure worsens seizures. Here, we show that blocking GABA transporters (GATs) in acute brain slices containing key parts of the thalamocortical seizure network modulates epileptiform activity. As expected, we found that blocking either GAT1 or GAT3 prolonged oscillations. However, blocking both GATs unexpectedly suppressed oscillations....

Registration Year

  • 2020
    13

Resource Types

  • Dataset
    13

Affiliations

  • Massachusetts General Hospital
    13
  • Brigham and Women's Hospital
    4
  • Stanford University
    2
  • Princeton University
    2
  • University of Pittsburgh
    2
  • University of Southern California
    2
  • Harvard University
    2
  • Rady Children's Hospital-San Diego
    1
  • Boston Children's Hospital
    1
  • Denali Therapeutics (United States)
    1