Therapeutics & Vaccines
Compounds And Methods For Modulating Frataxin Expression
WARF: P160232US05
Inventors: Aseem Ansari, Graham Erwin, Matthew Grieshop
The Wisconsin Alumni Research Foundation (WARF) is working with University of Wisconsin–Madison researchers developing a potential therapeutic agent to restore frataxin levels to treat and/or prevent Friedreich’s ataxia, a rare disease with no cure or effective treatment to date.
The agent has been shown in vitro to increase frataxin gene expression in a Friedreich’s ataxia patient cell line.
Overview
Friedreich’s ataxia (also referred to as FA or FRDA) is a rare but fatal autosomal recessive neurodegenerative disease. With an estimated incidence of 1 in every 40,000 people, it causes progressive damage to the nervous system and muscles, resulting in loss of coordination as well as various neurological and cardiac complications.
There is presently no cure or specific therapy to prevent progression of Friedreich’s ataxia. Onset of symptoms is typically seen between the ages of 5 and 15, and the mean age of death is approximately 38 years.
The disease is caused by mutations in the frataxin (FXN) gene. Specifically, an abnormal number of GAA trinucleotide repeat sequences results in reduced frataxin expression. The severity of the disease correlates with the number of repeats. Therefore, restoring or partially restoring frataxin in affected cells may slow or prevent disease progression.
There is presently no cure or specific therapy to prevent progression of Friedreich’s ataxia. Onset of symptoms is typically seen between the ages of 5 and 15, and the mean age of death is approximately 38 years.
The disease is caused by mutations in the frataxin (FXN) gene. Specifically, an abnormal number of GAA trinucleotide repeat sequences results in reduced frataxin expression. The severity of the disease correlates with the number of repeats. Therefore, restoring or partially restoring frataxin in affected cells may slow or prevent disease progression.
The Invention
UW–Madison researchers have developed a chimeric synthetic molecule capable of inducing increases in FXN mRNA levels in Friedreich’s ataxia patient cell lines.
The complex has the formula A-L-B wherein A- is a bromodomain inhibitor, -L- is a linker, and -B is a polyamide that specifically binds to one or more repeats of a GAA oligonucleotide sequence. Mechanistically, when the complex binds to the repeat sequence, the bromodomain inhibitor (ex., Brd4) recruits the superelongation complex (SEC) to restart the paused transcription complex.
The complex has the formula A-L-B wherein A- is a bromodomain inhibitor, -L- is a linker, and -B is a polyamide that specifically binds to one or more repeats of a GAA oligonucleotide sequence. Mechanistically, when the complex binds to the repeat sequence, the bromodomain inhibitor (ex., Brd4) recruits the superelongation complex (SEC) to restart the paused transcription complex.
Applications
- Potential therapeutic to prevent, treat or delay the symptoms of Friedreich’s ataxia
Key Benefits
- Potent and specific activation of gene expression
Stage of Development
The patent application shows that agents of the present technology increase frataxin levels in various FRDA patient cells.
Additional Information
For More Information About the Inventors
For current licensing status, please contact Rafael Diaz at [javascript protected email address] or 608-960-9847