Fragile X syndrome (FXS) is the most common monogenic cause of severe cognitive disability in boys. FXS is found in about 1 in 4,000 boys (girls also may be affected, but in a less severe manner). About 1,000 boys are born with FXS in the US and Europe each year, and there are more than 50,000 boys and men living with FXS in these regions. The most severely affected patients have little or limited use of language and often have significant behavioral problems, often related to profound social anxiety.
FXS arises because of a genetic mutation – the expansion of a triplet repeat in the FMR1 gene. This triplet repeat mutation leads to the silencing of an otherwise healthy gene. Because of this silencing, cells do not make the FMRP protein, which is important for proper neuronal function.
Fulcrum is developing a small molecule that counters the expansion to permit expression of the otherwise healthy FMR1 gene.
Currently there is no cure available for FXS, and current therapies do not target the fundamental cause of the disease nor slow progression.