Lex H. T. Van der Ploeg
My research is focused on mechanism-based drug development in human health. Programs under investigation include: resolution of the neuro-endocrine pathways involved in growth hormone (GH) release by non-peptidyl growth hormone secretagogues and growth hormone releasing peptide (i.e., GHRP-6), development of a murine model for Alzheimer's disease, and obesity research.
A growing body of pharmacological evidence has provided evidence for the notion that growth hormone releasing hormone and GHRPs exert their effects on GH release via separate, though synergistic pathways. A medicinal chemical approach has resulted in the design of several classes of non-peptidyl growth hormone secretagogues (GHSs) which mimic GHRP, resulting in release of GH in humans and other animals. These orally active GHSs may represent a significant advance in the treatment of growth hormone defeciency in children and adults and they may provide substantial benefit under circumstances where the anabolic effects of GH might be exploited clinically (e.G., post-hip fracture rehabilitation, the frail elderly). The mechanisms through which the GHSs mediate GH release are being elucidated.
In several pedigrees of early onset familial Alzheimer's disease (FAD), point mutations in the beta-amyloid precursor protein (APP) and presinilin genes are genetically linked to the disease. This finding implicates APP and the presinilins in the pathogenesis of Alzheimer's disease in these individuals. Our work is aimed at identifying appropriate targets that may benefit the treatment of Alzheimer's disease. The generation of murine models for the disease represents an important aspect of the work.
Genetic evidence has placed the leptin (ob) gene and the OB-R directly in the pathways that control satiety in humans. Our research is aimed at the development of compounds that affects satiety.