Awarded Grants
Awarded Grants
Genetic models to progress treatments for IQSEC2 related pharmacoresistant epilepsy.
Cheryl Shoubridge
University of Adelaide
$30,000
Awardee: Cheryl Shoubridge
Institution: University of Adelaide
Grant Amount: $30,000
Funding Period: March 1, 2024 - February 28, 2025
Summary: This project aims to generate patient derived iPS cells modelling the loss of IQSEC2 to comprehensively evaluate anti-epileptic drugs in reducing seizure activity in a human relevant setting.
Establishment of a female model of IQSEC2-associated disorders and AAV-mediatedtreatment of the phenotypes.
Takuma Mori
Shinshu University School of Medicine
$15,000
Awardee: Takuma Mori
Institution: Shinshu University School of Medicine
Grant Amount: $15,000
Funding Period: March 1, 2024 - February 28, 2025
Summary: This proposal aims to establish a standard strategy to understand female-specific phenotypes of IQSEC2-associated disorder using rodent models. The objectives of this project are to first produce a humanized mouse with IQSEC2-associated disorders and to investigate the physiological properties of a single neuron. The other aim of this proposal is to examine the possibility of the AAV-mediated treatment of IQSEC2-associated disorder.
A Novel Approach for the Treatment of IQSEC2-mediated Disease.
Sahar Isa Da’a
Sidra Medicine, Qatar Cardiovascular Research Center
$20,000
Awardee: Sahar Isa Da’a
Institution: Sidra Medicine, Qatar Cardiovascular Research Center
Grant Amount: $20,000
Funding Period: March 1, 2024 - February 28, 2025
Summary: Our proposal is centered on implementing a precise and personalized medicine approach to evaluate AMPA receptor modulators tailored for therapy specific to IQSEC2 genetic variants. Employing the zebrafish model, we aim to decipher the molecular and cellular mechanisms influenced by IQSEC2 genetic variants and their impact on neurodevelopment and phenocopying the clinical presentations of patients. The established zebrafish models will serve as a valuable tool for testing potential therapeutic drugs, specifically AMPA receptor modulators, designed for the treatment of IQSEC2-related disorders. The range of AMPA modulators includes Perampanel, known for inhibiting recycling; Ritalin and Aniracetam, recognized for increasing recycling; and PAM (PF-4778574), designed to boost AMPAR activity.
Development of a validated and patient-specific GNAO1 model for screening and testing of therapeutics
Harald Mikkers
Leiden University Medical Center, Netherlands
$100,000
Awardee: Harald Mikkers
Institution: Leiden University Medical Center, Netherlands
Grant Amount: $100,000
Funding Period: September 15, 2023 - September 14, 2024
Summary: This project will advance and improve a state-of-the-art personalized medicine tool for GNAO1. He will use funding from the Bow Foundation to create a validated stem cell GNAO1 model that opens the doors to various drug screening efforts. The work will investigate how GNAO1 impacts neurons and evaluate the suitability of the iPSC-based model for testing of therapeutics and drug responses
Testing mechanisms and intervention strategies in GNAO1 dystonia
Kirill Martemyanov
University of Florida Scripps Institute for Biomedical Innovation and Technology
$100,000
Awardee: Kirill Martemyanov
Institution: University of Florida Scripps Institute for Biomedical Innovation and Technology
Grant Amount: $100,000
Funding Period: August 1, 2023 - July 31, 2024
Summary: This project will help advance scientific understanding about the mechanisms of dystonia. Many GNAO1 patients suffer from dystonia, commonly known as involuntary muscle movements. Bow Foundation funding will allow Dr. Martemyanov to use a mouse model to shine light on the impact of GNAO1 on dystonia and brain signals while also testing possible treatment strategies.
Personalized Anti-Sense Oligonucleotide Therapy in a Patient with GNAO1 Mutation
Jennifer Friedman
University of California San Diego and Rady Children’s Hospital
$100,000
Awardee: Jennifer Friedman
Institution: University of California San Diego and Rady Children’s Hospital
Grant Amount: $100,000
Funding Period: August 1, 2034 - July 31, 2024
Summary: Dr. Friedman partnered with the n-Lorem Foundation to support the administration of an experimental antisense oligonucleotide (ASO) medicine that targets the GNAO1 gene. Funding from the Bow Foundation will help Dr. Friedman collect and evaluate the clinical observations of this cutting-edge treatment, including changes in baseline over time and data from predetermined outcome measures. This preclinical work will allow the research team to determine if ASO treatments for other GNAO1 patients are a viable approach for other patients.
Clinical trial for antisense oligonucleotide therapy in a patient with ADLD
Margot Cousin
Mayo Clinic
$50,000
Awardee: Margot Cousin
Institution: Mayo Clinic
Grant Amount: $50,000
Funding Period: May 1, 2023 - April 30, 2024
Summary: The long-term research goal is to advance disruptive innovation to transform care for individuals with ADLD through the development of a translational therapeutics program using team science. We hypothesize that a gapmer ASO to knockdown LMNB1 expression will be safe and well tolerated and that it will ultimately improve clinical outcomes in patients with ADLD. The objectives in this application are to develop and execute a first-in-human clinical trial to determine safety, tolerability, and potential clinical benefit of an LMNB1-targeted ASO therapy in a single patient with ADLD.
Development of 3D ADLD microfiber and organoid models for studying biomarkers and drug testing
Stefano Ratti
University of Bologna
$50,000
Awardee: Stefano Ratti
Institution: University of Bologna
Grant Amount: $50,000
Funding Period: May 1, 2023 - April 30, 2024
Summary: The project aims at developing reliable ADLD microfiber and organoid models for investigating
biomarkers and for drug testing. The novel models to be developed with this substantial 1 -year funding include 3D microfiber co-cultures of astrocytes and oligodendrocyte precursors (OPCs) and brain organoids. These models will be created from the fibroblasts of patients with the LMNB1 gene duplication and deletion phenotypes and healthy donors.
Analyzing CNS cell type specific transcriptomics in ADLD
Quasar Padiath
University of Pittsburgh
$50,000
Awardee: Quasar Padiath
Institution: University of Pittsburgh
Grant Amount: $50,000
Funding Period: May 1, 2023 - April 30, 2024
Summary: In this proposal, ADLD brain tissue samples will be utilized to carry out both bulk and
CNS cell type specific transcriptomics (RNA Seq analysis). Such an analysis will identify pathways there are perturbed as a result of lamin B1 overexpression and interrogate lamin B1 overexpression across different CNS cell types. These studies will help identify pathways contributing to the demyelination phenotype that may serve as potential therapeutic targets. In addition, cell type specific analysis can identify cells that are targeted for lamin B1 overexpression and cell type specific pathways that are perturbed providing critical insights into which cell types are responsible for the disease process.
Model systems to study the Bloom Syndrome Helicase in Homologous Recombination
Roger Greenberg
University of Pennsylvania
$100,000
Awardee: Roger Greenberg
Institution: University of Pennsylvania
Awarded: $100,000
Funding Period: September 1, 2022 - August 31, 2024
Project Summary:
Bloom Syndrome arises due to inherited mutations in the gene that encodes the BLM helicase. Patient cells experience myriad alterations to their DNA due to deficiency in specific aspects of a DNA repair process known as homologous recombination. We have developed systems that allow us to identify the function of the BLM helicase in DNA repair at a defined region of the human genome. We have used these approaches to publish high impact papers during this funding period that describe the role of BLM in DNA repair. In year two of this project, we expect to gain a better understanding of how BLM helicase acts to direct DNA repair and strategies to bypass the need for BLM when mutations in the BLM gene arise.
Publications:
Zhang T, Rawal Y, Jiang H, Kwon Y, Sung P, and Greenberg RA. Break Induced Replication Orchestrates resection dependent template switch. Nature 619(7968):201-208, 2023.
Jiang H, Zhang T, Kaur H, Shi T, Krishnan A, Kwon Y, Sung P, and Greenberg RA. BLM helicase unwinds lagging strand substrates to assemble the ALT telomere damage response. Molecular Cell 84(9):1684-98, 2024.
Identification and characterization of factors that suppress Bloom syndrome genomic instability
Maria Jasin
Memorial Sloan Kettering Cancer Center
$100,000
Awardee: Maria Jasin
Institution: Memorial Sloan Kettering Cancer Center
Awarded: $100,000
Funding Period: September 1, 2022 - August 31, 2024
Development of Normal and Tumor Organoids from Bloom Syndrome to Evaluate Responses to Pharmacological and Genetic Perturbations
Nathan Ellis
University of Arizona
$150,000
Awardee: Nathan Ellis
Institution: University of Arizona
Awarded: $150,000
Funding Period: September 1, 2022 - August 31, 2024
Multi-organ Gene Therapy for Bloom Syndrome
Amy Wagers
Harvard University
$100,000
Awardee: Amy Wagers
Institution: Harvard University
Awarded: $100,000
Funding Period: September 1, 2022 - August 31, 2024
iPSCs for Fibrodysplasia Ossificans Progressiva
Danielle Kerkovich
International Fibrodysplasia Ossificans Progressiva Association
Awardee: Danielle Kerkovich
Association: International Fibrodysplasia Ossificans Progressiva Association
Funding Period: July 27, 2022
iPSCs for Bloom Syndrome
Mary Campbell
Bloom Syndrome Association
Awardee: Mary Campbell
Association: Bloom Syndrome Association
Funding Period: July 27, 2022
iPSCs for Shwachman-Diamond Syndrome
Eszter Hars
Shwachman-Diamond Syndrome Alliance
Awardee: Eszter Hars
Association: Shwachman-Diamond Syndrome Alliance
Funding Period: July 27, 2022
Mouse Model for CACNA1A gene mutations and related neurodevelopmental disorders
Lisa Manaster
CACNA1A Foundation
Awardee: Lisa Manaster
Foundation: CACNA1A Foundation
Funding Period: May 13, 2022
Mouse Model for Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS) (NR2F1 gene mutation)
Carlie Monnier
NR2F1 Foundation / COMBINEDBrain
Awardee: Carlie Monnier
Foundation: NR2F1 Foundation / COMBINEDBrain
Funding Period: May 13, 2022
Mouse Model for SLC13A5 Epilepsy (Citrate Transporter Disorder)
Tanya Brown
TESS Research Foundation
Awardee: Tanya Brown
Foundation: TESS Research Foundation
Funding Period: May 13, 2022
Mouse Model for SCN1A Gain of Function (ultra-early onset Dravet syndrome)
Ethan Goldberg
CHOP
Awardee: Ethan Goldberg
Insitution: CHOP
Funding Period: May 13, 2022