Madhuri Hegde, associate professor in the department of human genetics at Emory University in Atlanta, was awarded an MDA research infrastructure grant totaling $300,000 over a period of three years to continue groundbreaking work to identify and characterize new gene defects that can cause limb-girdle muscular dystrophy (LGMD).
In the era of precision medicine, it is necessary that new therapies apply the right medication to the right patient at the right time, and it is an increasingly common requirement that a person’s clinical diagnosis be confirmed with a molecular diagnosis in order for him or her to participate in clinical trials.
MDA supports an LGMD testing program, in which more than 1,700 people have had their DNA sequenced, and a definitive molecular diagnosis of a particular LGMD subtype based on a known gene mutation has been found in 40 percent of cases. However, at least 30 to 40 percent of people diagnosed with LGMD still never get a molecular diagnosis, or get clinical reports noting “variants of unknown significance” in known genes.
Hegde aims to perform advanced genetic and functional assessments of these variants of unknown significance in an attempt to better understand how the variants might contribute to the cause of LGMD in these cases. This work will increase our understanding of the genes involved in neuromuscular disorders, and has the potential to point to better therapeutic approaches for a larger number of individuals with LGMD.
Please describe your current research.
Gene panels, exome and genome sequencing are now widely used in clinical diagnostics for neuromuscular disorders. These DNA-based assays result in detection of a large number of variants of unknown clinical significance (VOUS). According to the recent variant interpretation guidelines, several pieces of data, including functional evidence, are needed to classify these variants as being pathogenic (capable of causing disease) or not. Transcriptome analysis can be used for functional assessment of these variants to generate evidence for pathogenicity of a variant in known and newly identified cases of LGMD and therefore help patients participate in clinical trials and drive precision genomic medicine for neuromuscular disorders.
Is this your first MDA grant?
This is not my first MDA grant. MDA has been very supportive of my research work over the years. This support has led to major advances in diagnostics in LGMD.
What inspired you to study LGMD?
I have worked on muscular dystrophies for more than 15 years. The patients and their fight against these conditions are my true inspiration.
What is your area of focus within the neuromuscular disease field, and why is it important?
I work on Duchenne muscular dystrophy, congenital muscular dystrophy and limb-girdle muscular dystrophy.
As new therapeutic approaches are discovered, it is clear that we need to understand the genetics of these diseases in order to develop effective therapies.
What is the expected outcome of this research?
Our understanding of the genes and their functions will increase significantly and, most importantly, patients will benefit directly.
Does your work have any potential implications for other disease fields?
Yes. All genetic inherited disorders stand to benefit from this work.
To learn more about how MDA research is accelerating treatments and cures for LGMD, please visit mda.org.
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