Fragilex Canada Foundation

What is Fragile X ?

The term Fragile X refers to a group of conditions due to defects in a gene on the X chromosome:

  • Fragile X syndrome (FXS)
  • Fragile X-associated Tremor Ataxia Syndrome (FXTAS)
  • Fragile X-associated primary ovarian insufficiency (FXPOI)

Fragile X syndrome (FXS), first known as Martin-Bell syndrome, is the most common inherited form of mental impairment. FXS affects 1 in 4,000 boys and 1 in 6,000 girls of all races and ethnic groups. While Fragile X individuals have a normal life expectancy, most will need support and care for their entire lives.

A single gene in the brain cells shuts down, causing Fragile X syndrome. In 1991, scientists discovered the defect in a gene on the X chromosome (called FMR1) that causes FXS. In affected individuals, this gene is shut down and cannot manufacture the protein it normally makes – a protein vital for normal brain development and functioning.

Large-scale population studies of Fragile X still need to be done, but it is clear that this is one of the most common genetic diseases in humans. Most people with Fragile X are not yet correctly diagnosed.

Research is aimed at developing effective treatments. In addition, this research is leading to better understanding and treatments for other conditions, such as autism, and Alzheimer’s Disease.

Grant reports

FXRFC Awards Three Research Grants for 2009

The Fragile X Research Foundation of Canada continues its drive to increase the number of scientists working towards finding a treatment for Fragile X. The FXRFC awarded 3 new research grants in 2009, committing over $120,000.00 for research aimed at finding a treatment or cure for Fragile X. These grants were awarded in partnership with the Canadian Institutes of Health Research (CIHR), which will pay for half the cost. The new projects, at McGill University, will yield valuable information on the pathology of Fragile X, and should stimulate further research in this area.


Principal Investigator: Dr. Pejmun Haghighi, Ph.D., Physiology Department, McGill University, Montreal
Postdoctoral Fellow: Dr. Robin Ball, Ph.D.
Amount: $45,000.00/year awarded for a term of two years in partnership with the CIHR
Start Date: April 1, 2009

Fragile X Mental Retardation Protein interacts with Rac GTPase to control synaptic growth and function

Fragile X Syndrome is caused by a mutation in the FMR1 gene. FMR1 is present in Drosophila (fruit fly) and mutations in this gene lead to abnormal synaptic connections between neurons. This lab will study the Fragile X protein and how it functions during development of the Drosophila neuromuscular junction, where nerve cells connect with muscles. There is evidence that the activity of an enzyme called Rac1 GTPase is normally decreased  by the Fragile X protein and this lab will explore this interaction in more detail. They hope to get a better understanding of the function of the Fragile X protein and how this affects the formation of synaptic connections. The fruit fly has been well established as a model system suitable for studying human diseases, because it has many of the same genes and protein signaling pathways as humans. The benefit to using the Drosophila neuromuscular junction is that there are many genetic tools available, and the synapse is so easily accessible for imaging and electrophysiological studies. What we learn about Fragile X in Drosophila can easily be applied for studies in mammals and ultimately for medical intervention.

Principal Investigator: Dr. Derek Bowie, Ph.D., Department of Pharmacology & Therapeutics, McGill University, Montreal
Postdoctoral Fellow: Dr. Mabel Chong, Ph.D.
Amount: $45,000.00/year, awarded for a term of three years in partnership with the CIHR
Start Date: April 1, 2009

Can deficits in Fragile X syndrome be corrected early in development by targeting a novel AMPA receptor?

An important issue encountered in the study of neurological disorders is understanding the pathway between a genetic mutation and its resultant behavioural symptoms. In Fragile X patients, a major consequence of the Fmr1 gene mutation results in cognitive impairment.  In this context, the aim of this research proposal is to show that functional deficits in the Fragile X brain are caused by the loss of a mechanism that controls synaptic plasticity, and is regulated by a novel AMPA receptor on the brain cells at a very early stage in postnatal development.  This lab will also conduct experiments designed to reverse this functional loss by increasing the activity of an existing cell signaling pathway. The physiological and molecular implications of this project will introduce the possibility of designing a therapeutic strategy that eliminates the onset of cognitive impairments in children diagnosed with Fragile X syndrome.

Principal Investigator: Dr. Barbara E. Jones, Ph.D, Department of Neurology & Neurosurgery, McGill University, Montreal Neurological Institute, Montreal
Postdoctoral Fellow: Dr. Anne-Marie L, Fay Ph.D.
Amount: $45,000.00/year, awarded for a term of three years in partnership with the CIHR
Start Date: September 1, 2009

Does atypical sleep architecture underlie neuronal disruption in the Fragile-X brain?

This lab will test the mGluR5 theory of Fragile X on the regulation and balance of synaptic connections between brain cells. This lab will take a unique approach to this by looking at the role of sleep in this debilitating condition. In fact a growing body of evidence suggests that people with autism and/or cognitive dysfunction frequently display atypical sleep patterns. Although, long-term sleep disruption most likely contributes to the pathology of FXS, it has yet to be studied systematically. This lab proposes to do this by examining the relationship between sleep patterns with changes in synaptic transmission.

Sleep is thought to decrease synaptic strength to a lower level, thus compensating for the net increase in synaptic strength that occurs during wakefulness. Consequently, sleep is a necessary step in restoring the set-point of synaptic plasticity. Moreover, sleep plays an important role in memory creation and consolidation, as well as directing synapse maturation. In contrast the FXS brain exhibits an immature structure  with defects in connectivity and synapse stabilization, which are thought to underlie the cognitive problems in FXS. To examine this, this lab will look at the effect of the mGluR5 blocker, MPEP, on sleep pattern and synaptic regulation using electrical measurements of brain activity as well as video for behaviour testing of the FXS mouse model compared to control littermates. Since the FXS brain shows immature brain development, correcting an imbalance in sleep pattern may provide a novel therapeutic approach in reversing brain disruptions that are the hallmark of Fragile X syndrome.