RESEARCH ACTIVITIES

Dr. van Home's research is currently focused on the surgical treatment of neurodegenerative diseases. Much of this work has involved two movement disorders that are pathologically located in the basal ganglia.

Parkinson's Disease (PD) results from a loss of dopaminergic neurons within the substantia nigra (SN), and Huntington's Disease (HD) which results from a loss of GABAergic neurons within the striatum. Although medical management has proven to be effective in the treatment of symptoms in the majority of cases early in the course of PD, no treatments have been shown to halt or slow the neurodegeneration. As the disease progresses, drug treatments become less effective and are often complicated by debilitating side effects. There are currently no effective medical treatments for the choreoathetosis or mental deterioration observed in patients with HD. Thus, there is clearly a role for the investigation of alternative treatment strategies, especially those aimed at preventing cell loss or the restoration of degenerated cell populations.

Fortunately, experimental treatment strategies can be tested on animal models of these diseases. Stereotatic application of specific neurotoxins produce a pattern of cell loss that effectively parallels the neurodegenerative patterns found in patients. The animals can then be tested behaviorally, electrophysiologically, neurochemically, and histologically for changes in their physiological and functional deficits. Current areas of focus include the role of growth factors and their ability to restore function to damaged dopamine neurons and / or to promote the survival and outgrowth of processes from transplanted dopaminergic cells. Issues concerning transplantation relate to a) the best source of donor tissue, human fetal tissue, non-human xenografts, or genetically modified cell lines, b) the specific host target sites, and c) the ability of co-transplanted tissues to enhance primary graft and host function. Taken together, the basic investigations provide potential directions of future patient trials.

At the clinical level, there have been several studies investigating the ability of transplanted tissues and growth factors to improve the clinical outcome of both PD and HD.  Although there have been reports of overall limited success, there is currently no protocol which can either claim to cure these diseases or be proposed to become more (than experimental therapy. While many of the issues concerning the clinical implementation of these strategies parallel those being investigated at the basic animal model level, one important difference strongly supports the continued ,effort of clinical trials. The limited success of the clinical studies, compared to that observed in the animal studies suggests the presence of unique inherent differences between patient pathophysiology and the functional changes found in our animal models.

Thus, only through the direct application of experimental strategies at the patient level will we be able to determine the necessary factors for improved therapeutic outcomes. The overall goals of Dr. van Home's research are to improve our understanding of the role of basal ganglia in normal movement and movement disorders, to develop new treatment strategies and specifically evaluate their effectiveness at the cellular and systems levels, and, based on these principles design and refine future clinical trials. Using this paradigm, it may be possible to establish techniques that will allow us to augment and repair damaged neural circuitries within the brain.

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