In Search for Treatments and a Cure, IRSF Invests $2.3M in Research
The IRSF worked with its scientific advisory board (SAB) to determine the studies to advance. To develop treatments for the rare neurodevelopmental disorder, the organization’s overarching focus is understanding the MECP2 gene and the protein it codes for — affected in most Rett cases — and developing new treatment targets.
In line with its scientific strategy, the foundation believes that its funded studies will expand the therapeutic pipeline and lead to successful clinical trials. Currently, there are no approved disease-modifying treatments for Rett syndrome, although some therapy candidates are being developed.
“Because Rett syndrome is a rare disorder, our Foundation’s investments strongly influence the direction and pace of Rett research as well as the potential treatment options that come out of it,” Melissa Kennedy, IRSF CEO, said in a press release. “We take this responsibility very seriously and choose our investment areas carefully.”
With the goal of developing therapies and enhancing its understanding of how changes in MECP2 affect different cell types as well as brain connections, the IRSF has backed projects that will:
- Survey brain connections affected by MECP2 mutations.
- Investigate a cell type in which MECP2 loss may determine the early connections formed in Rett patients’ brains. (This could lead to a new Rett treatment target.)
- Discover whether brain immune cells that contain the MeCP2 protein can restore functioning in Rett.
- Explore how the loss of MeCP2 alters the activity of other genes in the brain of every cell type.
In addition to gaining more knowledge of MeCP2, some researchers will use the grant funds to explore factors such as those involved in cellular stress and energy — focusing on mitochondria, the producers of energy within a cell — and their link to Rett. Specifically, investigators will set out to:
- Learn how Rett syndrome affects a key regulator of cellular stress and inflammation.
- Pinpoint how mitochondria affect cellular stress before and after Rett’s regression phase. (The disorder is characterized by a phase of normal cognitive and motor development until ages 6 to 18 months, followed by a regression of learned motor and verbal skills.)
- Define the cellular stress factors’ contribution to Rett syndrome processes.
- Analyze the contribution of so-called “jumping genes” to Rett. (In people who don’t have Rett, such genes — pieces of DNA that can move at will around the genome — are overwhelmingly forced to stay put. Rett syndrome, however, mobilizes such genes in the brain.)
Through the funded research, the IRSF also hopes to improve the processes used to evaluate potential therapies in clinical trials. This latest round of grants will help to facilitate this through continued work with pharmaceutical companies on their Rett syndrome treatment-development programs and by studying brain waves as a potentially better translatable outcome measure for clinical trials.
“IRSF has continued to provide funding for several exciting and critical areas of Rett Syndrome research,” said Kyle Fink, PhD, SAB member and neuroscientist at the University of California, Davis, MIND Institute. “The funding mechanisms set up by IRSF allow for research to occur at several key levels of treating this devastating disorder.”