
Readthrough of premature termination codons for treatment of Rett Syndrome
Allan Jacobson, PhD / Jonathan Watts, PhD | UMASS
$323,000 AWARDED
This project lays the foundation for developing a therapeutic specific to mutations that cause a premature stop, otherwise known as nonsense mutations. These are mutations that end in X, for example, R168X, R270X, R255X, which tell the cell to stop reading the DNA instructions for MeCP2 too early.
What if there was a way for the cell to ignore that premature stop and just continue through it to the correct stopping point? Imagine a railroad track with a sign signaling that part of the track is out. We know that even a small piece of missing track would derail the train. Imagine that this same sign on the track also sends out a message that all incomplete tracks should be completely destroyed. Now imagine a drug that provides a quick fix to the problem by laying down a temporary piece of track to prevent track destruction and allow the train to reach its destination.
The applicants propose to develop a combination treatment that allows the cell to ignore and continue through the premature stop, thus allowing more trains to get to their normal stop destination and create full length functional MECP2.
A key advantage to this approach is that the path to drug development could be fast-tracked. One part of the treatment, called Ataluren, is already approved in 45 countries for Duchenne Muscular Dystrophy. The other molecule resembles a treatment FDA has recently approved, Spinraza. Together the combination treatment may provide a clearer path to FDA approval based on existing precedent.
We are providing 1 year of funding to generate proof of concept data that this approach in fact can generate full length functional MeCP2 in cultured cells. If the preliminary data are convincing the applicants will submit a follow up proposal to begin in vivo mouse work.
Current Projects
-
Rett Syndrome Microbiome Study for the Advancement… Beth McCormick
$481,774READ MORE -
Passive Monitoring of Rett Patients with the… Emerald Pilot and MC10 nPoint Development Study
$164,670READ MORE -
Rett Syndrome Biorepository Coriell Institute for Medical Research
$135,000READ MORE -
The generation and phenotypic assessment of mouse… Jackson Labs
$417,690READ MORE -
RNA editing for MECP2 mutations via RESTORE Thorsten Stafforst, PhD
$366,520READ MORE -
Correction of MECP2 Mutations with Engineered… Joseph Jacobson, PhD
$50,000READ MORE -
Development of a cDNA/mRNA Delivery System…
$68,000READ MORE -
Human In Vitro Models For X Chromosome… Joost Gribnau, PhD
$401,000READ MORE -
Development of siRNA-based compounds to potently… Anastasia Khvorova, PhD
$435,515READ MORE -
Interrogation of Genome Editing Strategies as a… Ronald Cohn, MD | The Hospital for Sick Children
$570,000READ MORE -
A Drug-Screening Platform for the MECP2… Alysson Renato Muotri, PhD | University of California San Diego
$792,000READ MORE -
A Study to Evaluate Ketamine for the Treatment of… Clinical Trial Consortium
$1,300,000READ MORE -
Triheptanoin (UX007) | Treatment of Mitochondrial… Daniel Tarquinio, DO, MS | Center for Rare Neurological Diseases
$51,600READ MORE -
Protein Replacement for Rett Syndrome Armagen
$125,000READ MORE -
Gene Therapy Approach to Treating MECP2… Kevin Foust, PhD | Ohio State University
$40,000READ MORE -
Optimizing Gene Therapy for Rett Syndrome Kathrin Meyer, PhD
$221,004READ MORE -
A System For Dosage-independent Control of Mecp2… Michael Elowitz, PhD | Caltech
$197,681READ MORE -
Developing a pre-clinical DNA base editing program… BEAM Therapeutics
$1,870,660READ MORE -
Exploration of the Impact of Cyclodextrin on… Stephen Turley, PhD & Adam Lopez, PhD | University of Texas Southwestern…
$156,180READ MORE -
Investigating the Potential of Antisense… Huda Zoghbi, MD | Baylor College of Medicine
$530,000READ MORE -
Identification of Gene Modifiers that Ameliorate… Monica Justice, PhD | Hospital for Sick Children (Toronto)
$2,300,000READ MORE -
Identifying Therapeutics for Treating Rett… Michael Greenberg | Harvard University
$110,000READ MORE -
Development of an In-Vitro Cell System For… Q-State BioSciences
$828,141READ MORE -
Modeling MECP2 Dosage in Human Cerebral Organoids Alysson Renato Muotri, PhD | University of California San Diego
$209,000READ MORE -
RNA and Genome editing for treatment of Rett… Jonathan Watts, PhD / Erik Sontheimer, PhD / Scot Wolfe, PhD / Anastasia…
$2,403,735READ MORE -
Discovery of Compounds Promoting MECP2… Andrew Napper, PhD | Nemours/A.I. duPont Hospital for Children
$268,452READ MORE -
Reversal of Rett Phenotype: A screen for compounds… Rudolf Jaenisch, MD | Whitehead Institute
$180,000READ MORE -
A Forward Genetic Screen to Identify Druggable… Huda Zoghbi, MD | Baylor College of Medicine
$1,485,949READ MORE -
Identification of Genetic Modifiers in Rett… Jeffrey Neul, MD, PhD | University of California San Diego
$315,000READ MORE -
RNA-editing as a gene therapy approach for Rett… Guoping Feng, PhD /Feng Zhang, PhD /Robert Desimone, PhD MIT/Broad/Harvard
$2,332,000READ MORE -
New Editing Enzymes for RNA Gail Mandel, PhD | John Sinnamon, PhD
$345,000READ MORE -
From Sensory-Perceptual Representations to… John Foxe, PhD., University of Rochester, Albert Einstein College of…
$533,607READ MORE -
Treatment of Rett Syndrome with Lovastatin Aleksandra Djukic, MD, PhD Albert Einstein College of Medicine,…
$403,000READ MORE -
Is MECP2 Duplication/Triplication Syndrome… Huda Zoghbi, MD | Baylor College of Medicine
$236,000READ MORE -
Screening for drugs that can rebalance long gene… Mark Zylka, PhD | University of North Carolina at Chapel Hill
$400,000READ MORE -
New Molecular Tools for Directed Editing of MeCP2… Peter Beal, PhD | UC Davis
$563,870READ MORE -
Outlining the Autonomic Signature of Rett Syndrome Debra Weese-Mayer, MD & Michael Carroll, PhD | Ann & Robert H. Lurie…
$157,000READ MORE -
Therapeutic Approaches to Reversing Forebrain and… David Katz, PhD | Case Western Reserve University
$500,000READ MORE -
Treatment of Rett Syndrome with Copaxone Aleksandra Djukic, MD, PhD Albert Einstein College of Medicine,…
$487,000READ MORE -
PNA Nanoparticles for Gene Editing of Rett… Peter Glazer, MD, PhD & Mark Saltzman, PhD | Yale University
$275,000READ MORE -
Clinical Development of NLX-101 in Rett Syndrome;… Mark Varney, PhD | Neurolixis
$585,000READ MORE -
Systems Genetics Approach toward Understanding… Terry Magnuson, PhD | University of North Carolina at Chapel Hill
$200,000READ MORE -
RNA trans-splicing therapy in Rett Syndrome Stuart Cobb, PhD and Chris Sibley, PhD | University of Edinburgh
$1,158,475READ MORE -
High-Content Phenotypic Screening of Existing… Christopher Gibson, PhD & Dean Li, MD, PhD | Recursion Pharmaceuticals
$50,000READ MORE -
Readthrough of premature termination codons for… Allan Jacobson, PhD / Jonathan Watts, PhD | UMASS
$323,000READ MORE -
Exploring the Link Between MeCP2 and Gut… Ali Khoshnan, PhD & Sarkis K. Mazmanian, PhD | California Institute of…
$200,000READ MORE -
Testing NR2A and NR2B NAMs in the mouse models of… Michela Fagiolini, PhD | Boston Children’s Hospital
$464,336READ MORE -
Reactivation of MECP2 and CDKL5 genes by… Andrea Cerase, PhD | Queen Mary University of London
$351,022READ MORE -
Testing Whether LM22A-4 Improves Hippocampal… Lucas Pozzo-Miller, PhD | University of Alabama Birmingham
$110,000READ MORE -
Reactivation of MECP2 by Artificial Transcription… Raf Schmid, PhD, MSCR | University of Pennsylvania
$141,912READ MORE -
Preclinical Studies of LM22A-4 in Mouse Models of… David Katz, PhD | Case Western Reserve University
$272,000READ MORE -
Reactivation of MECP2 with Epigenome Editing Tools… Rudolf Jaenisch, MD | Whitehead Institute
$600,000READ MORE -
Evaluating Cell-permeant Miniature Proteins… Alanna Schepartz, PhD | Yale University
$270,216READ MORE -
Outcome Measures and Biomarkers Development Timothy Benke, MD, PhD | Aleksandra Djukic, MD, PhD | Alan Percy, MD |…
$4,500,000READ MORE -
Gene Therapy Consortium 1.0 Gail Mandel, PhD | Stuart Cobb, PhD | Steven Grey, PhD
$1,600,000READ MORE -
Gene Therapy Consortium 2.0 Adrian Bird, PhD | Stuart Cobb, PhD | James Wilson, MD, PhD
$5,463,184READ MORE -
Outcome Measures and Biomarkers Development Timothy Benke, MD, PhD | Alan Percy, MD | Daniel Tarquinio, DO, MS
$4,500,000READ MORE -
MECP2 Consortium Adrian Bird, PhD | Michael Greenberg, PhD | Gail Mandel, PhD
$9,000,000READ MORE -
Clinical Trial Consortium David Lieberman & Mustafa Sahin | Eric Marsh | Jeff Neul | Alan Percy |…
$2,442,507READ MORE -
Reactivating MECP2 Consortium Ben Philpot, PhD & Bryan Roth, PhD | Antonio Bedalov, MD, PhD | Jeannie…
$6,416,072READ MORE