Publications

We conducted a randomized, double-blind, placebo-controlled crossover study of folinic acid therapy (dl-Leucovorin, 15 mg/day) or placebo for males with Fragile X (fra(x)) syndrome. Twenty-one patients were enrolled in the study. The treatment periods were 3 months in length. Patients were followed with chemistry panels and complete blood counts. No differences between placebo and treatment phases were noted in any laboratory parameter. Instruments to measure functioning were the Vineland Adaptive Behavioral Scales, Peabody Picture Vocabulary Test-Revised, Conners Parent and Teaching Rating Scales, the ADD-H: Comprehensive Teacher's Rating Scales (ACTeRS), and a questionnaire designed by the investigators. At the crossover point, 2 parents requested to withdraw from the study because they felt their children had made dramatic gains during the first half of the study and had lost those gains after the crossover point. Both parents had accurately predicted that their sons were receiving folinic acid during the first half of the study. However, no statistically significant differences could be demonstrated between the treatment and placebo phases of the study with any instrument when the results were averaged over the entire cohort. After the conclusion of the study, approximately one-half of the parents believed that their children had benefitted from the folinic acid therapy and elected to continue treatment. Thus far, no significant side effects have been noted from long-term folinic acid therapy so we are offering all Fragile X patients a 3-month trial of medication.

The extracellular matrix, comprising the glomerular basement membrane and the mesangial matrix, plays a crucial role in glomerular structure and function. The glomerular extracellular matrix is composed of collagens, proteoglycans and glycoproteins. The distorted balance between synthesis and degradation of extracellular matrix proteins is a hallmark of many forms of glomerulonephritis, such as glomerulosclerosis. The degradation of the matrix occurs through the action of a group of extracellularly active metalloproteinases. Within the glomerulus these enzymes are synthesized by the epithelial and the mesangial cells. The molecular structure of the mesangial metalloproteinases, including their in vitro regulation, was analyzed and the in vivo synthesis of these proteinases was documented for cases of idiopathic rapid progressive glomerulonephritis and anti-Thy 1.1 nephritis. The therapeutic change in the activity and expression of the glomerular metalloproteinases, resulting in the restoration of physiologic matrix metabolic balance, opens up a new perspective for the therapy of glomerular inflammatory processes.