LncRNA as Therapeutic Target for SMA

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Grant Year

ANF/MDA Co-Funded Grant

Grant Type

Constantin d'Ydewalle, PhD


Johns Hopkins School of Medicine, Baltimore, MD


Spinal muscular atrophy (SMA) is the leading inherited cause of infant mortality and is caused by mutation of the survival motor neuron-1 gene (SMN1), retention of a highly homologous SMN2 gene, and reduced levels of SMN protein. Hence, SMA treatments currently under development aim to increase SMN protein levels. Prior studies and our preliminary data show that SMN is highly expressed during early gestational stages, but decreases postnatally. This may indicate that specific levels of SMN are temporally required for normal motor neuronal development. It is unknown, however, how SMN expression is regulated over time. Approximately 90% of the human genome is transcribed while only 2% has protein-coding potential. Recently, long non-coding RNAs (lncRNAs) have been shown to be powerful regulators of gene expression. LncRNAs transcriptionally regulate many genes via interactions with the polycomb repressive complex-2 (PRC2). My work focuses on a SMN-associated lncRNA that regulates the expression of SMN during neuronal development and differentiation. The project proposed here aims to understand how this mechanism works in neurons both in mice and in a petri dish. A better understanding of the mechanisms that regulate SMN expression are crucial for SMA therapeutics development.
"I strongly believe that this collaborative effort will eventually pay off in a real cure for SMA."
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