In partnership with MDF, the Wyck Foundation awarded a number of new DM research grants:
Nicholas Johnson, M.D.
University of Utah
Population-based U.S. Prevalence of Mutations for Myotonic Dystrophy Types DM1 & DM2; Phase II: Implementation of Population-Based U.S. Screen
Current understanding of the prevalence of myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) is based upon potentially biased/limited data. This is at least partly due to the wide variation in the age of onset and individuals with the disease who have not been diagnosed, both of which would not have been accounted for in prior prevalence studies, none of which were conducted in the U.S. In Phase I of this effort, to better understand the prevalence of DM1, Dr. Johnson developed and validated a cost-effective, molecular screen capable of estimating the prevalence of DM1 and DM2 mutations and pre-mutations in the general U.S. population. In Phase II, he will use a population sample of de-identified newborn blood spots to determine carriers of myotonic dystrophy (DM) mutations and pre-mutations and, thereby, assess the population-based prevalence of DM1 and DM2.
Anwesha Banerjee, Ph.D.
Postdoctoral Research Fellowship: Mechanism of CNS-Associated Behavioral Dysfunction in Novel Mouse Model of Myotonic Dystrophy Type 1
Dr. Banerjee proposes studies designed to provide new mechanistic insights into how RNA toxicity and perturbation of RNA splicing can lead to CNS-associated behavioral symptoms in DM, and provide proof of concept that antisense oligonucleotides (ASOs) can restore brain function in a neuron-specific mouse model of DM1. This mechanistic research, conducted in Dr. Gary Bassell’s lab, provides an important career development opportunity and is anticipated to advance disease mechanism-targeted therapeutic interventions in DM1 patients. A new mouse model will be developed and used to study brain dysfunction and provide new mechanistic insights into CNS-associated behavioral symptoms in myotonic dystrophy.
Kaalak Reddy, Ph.D.
University of Florida
Postdoctoral Research Fellowship: Pre-Clinical Investigations of Small Molecule Targeting of Toxic RNA Production in DM2
Dr. Reddy proposes to investigate a novel DM therapy development strategy by targeting transcription of the expanded repeats using small molecules to reduce or eliminate the production of the toxic RNAs. The specific aims are to: (1) determine the efficacy of small molecules to reduce downstream toxic effects of expanded repeat transcription in DM2 cell models and (2) test for small molecule-mediated rescue of DM2 disease phenotypes in mouse models. This translational project provides an important pathway to an independent research carrier and will be conducted in Dr. Andy Berglund’s lab. The study will help determine if recently identified lead compounds can be developed as treatments for DM.