Dr. Berry-Kravis is working on several major fragile X research projects at Rush University Medical Center in Chicago. These include the studies described below. For information on participating in any research study under way at Rush, see the clinical trials database on the Rush Web site.

Neurological Symptoms in Older Fragile X Premutation Carriers
This is an NIH-funded consortium project with Paul Hagerman, MD, and Randi Hagerman, MD, at the University of California in Davis, and with Maureen Leehey, MD, at the University of Colorado in Denver. Scientists involved in the study are investigating neurological symptoms in male and female carriers of the FXS premutation, and comparing these symptoms to other carriers and noncarriers of the same age. Eligible participants must be related to someone with FXS, and must be over the age of 50. Carrier status need not be known prior to entering, as we offer free DNA testing as part of the study. Carriers and noncarriers of both sexes are needed. The study requires that participants come to Rush one time for approximately two hours to complete a videotape protocol and to answer questions on standardized forms about any symptoms they may have. Each participant is videotaped while completing a series of movements and answering questions; these videos are then reviewed by Christopher Goetz, MD, a movement disorders specialist at Rush. Please call for more information or with questions regarding this study.

Add-On Trial of Lithium in Fragile X Syndrome
In individuals with fragile X syndrome (FXS), the fragile X gene (FMR1) is turned off, so the fragile X protein (FMRP) is not made. Absence of FMRP in the brain produces the learning and behavior problems seen in individuals with FXS. One of the pathways that is regulated incorrectly and is overactive in fragile X is called the mGluR pathway. Too much activity in this pathway (due to missing FMRP) leads to immature and weaker connections between brain cells. The overactivity of the mGluR pathway is believed to cause many symptoms of fragile X, including hyperactivity and anxiety. In other research, lithium has been shown to inhibit (partially block) the mGluR pathway.

The purpose of this study is to assess the short-term and long-term effects of treatment with lithium for people with fragile X syndrome.

The study will be conducted at both Rush University Medical Center and the Brain-Body Center at the University of Illinois at Chicago and is funded by FRAXA. Each participant will complete a battery of cognitive and psychophysiological tests. In addition, caregivers will fill out behavioral questionnaires several times during enrollment in the study. Measures will be administered at baseline, after two months of treatment and, if the participant agrees to continue, after a year of treatment.

Effects of FMRP Expression in Cultured Neural Cells
This basic research project is examining neural cell properties, signal transduction and regulation of cAMP signaling in neural cells that over-express and under-express FMRP. This project is being funded by the Illinois-Eastern Iowa District of Kiwanis International, Spastic Paralysis and Allied Diseases of the Central Nervous System Research Foundation.

Development of Outcome Measures for Future Clinical Trials in Fragile X Syndrome
New information is becoming available regarding the neurobiological mechanism of mental retardation in fragile X syndrome, FXS. This has resulted in proposal for syndrome-specific treatments to compensate the neural mechanisms made abnormal by the absence of the fragile X protein, FMRP. Some of these treatments are being developed but there is a critical need for well-validated outcome measures to demonstrate drug effect in the fragile X population. This pilot project for outcome measure development will test the validity, in an FXS population, of a number of cognitive tasks designed to assess specific areas of weakness in FXS that might be expected to show rapid improvement during the timeframe of a phase II clinical trial lasting several weeks to several months. The project will also assess the usefulness and reproducibility of a new biomarker for a pathway shown to be abnormal in the absence of FMRP, for determining biological effectiveness of treatment in future clinical trials.