February 28, 2007
For the first time, a drug being developed for the treatment of
Fragile X has received an Orphan Drug Designation from the Food and Drug Administration (FDA).
In collaboration with FRAXA, Neuropharm Group plc is developing fenobam for the treatment of Fragile X.
Neuropharm Limited, a subsidiary of Neuropharm Group plc, is a UK based speciality pharmaceutical
group focused on the development of products for the treatment of disorders of the central nervous
system. The FDA has granted Neuropharm Orphan Drug Designation for the use of fenobam in the treatment
of Fragile X.
The Orphan Drug Act was passed by Congress to accelerate the development of treatments for rare diseases,
defined as affecting 200,000 or fewer people in the U.S. Fragile X affects almost 100,000 US residents.
Fragile X, the most common inherited cause of mental retardation and the most common genetic cause of
autism, results from the lack of a protein called FMRP. As a result of a deficiency of FMRP,
brain cells don't communicate normally.
FRAXA-funded researchers have found a specific excess of metabotropic glutamate receptor (mGluR) signaling
in Fragile X brains, and studies indicate this may be a common mechanism underlying many autism spectrum
disorders. Follow-up research on animal models (also funded by FRAXA) shows it is possible to intervene
in this hyperactive brain mechanism with compounds which block mGluRs, reversing the core deficits of
Fragile X such as impaired cognition, anxiety, and autistic behaviors.
FRAXA has spent $3.8 million on funding research to build the case for using mGluR antagonists to treat
Fragile X, beginning with a grant awarded in 2000 to Dr. Mark Bear (now Director of the Picower Institute
at Massachusetts Institute of Technology) and Dr. Kimberly Huber (now a Professor at the University of
Texas Southwestern Medical Center). FRAXA has funded over $11 million in Fragile X research over the
past 13 years, and is continuing research on several other potential treatment strategies.
Fenobam was developed in the 1970s by scientists at McNeill Labs. It was studied in clinical trials
in patients with anxiety disorders, demonstrating a good safety profile and some effectiveness, but
precisely how it worked was unknown. Two decades later, researchers at Hoffmann LaRoche discovered
that it is an mGluR5 antagonist, making it a promising candidate treatment for Fragile X.
Says FRAXA co-founder Michael Tranfaglia, MD, "We are very hopeful that this drug could get normal brain development back on track in people with Fragile X - and possibly autism as well."
