What is an autograft?
Ease of tissue collection without ethical and immunological problems inherent in allogenic and xenogenic tissue
What did much of the early work focus on?
Much of the early work focused on autologous cellular sources of dopamine
Initial attempts used tissue from where?
Adrenal Medulla (AM)
Why is AM tissue used?
Secretes dopamine and other catecholamines
Early studes in animal studies are variable, but who provided some evidence for survival and functional benefits experimentally?
Freed et al. 1981; Freed et al. 1986
Uncertainties about what and limited what?
Uncertainties about mode of action of AM grafts, limited functional benefits experimentally
Small open label clincial trials strated when? What did they find?
Backlund et al. (1985) --> no placebo, but still some slight improvement
When do other studies show modest improvements for?
Other studies showed modest improvements for limited 18-month period
Post-mortem studies showed what?
Hurtig et al. (1989) --> Post-mortem studies showed poor survival of grafted tissue
Neuopathological study done 16 years after an autologous adrenal medullary transplantation showed what?
o Neuopathological study done 16 years after an autologous adrenal medullary transplantation showed few chromogranin A positive cells and complete absence of cells staining for tyrosine hydroxylase (key enzyme in dopamine synthesis) at the graft site. The patient had dervied some clinical benefit from the graft for ~4 years post transplantation. (Kompoliti et al. 2007)
In order to improve graft survival of AM transplants, what was investigated?
In order to improve graft survival of AM transplants, co-grafts of tissue secreting Nerve Growth Factor (NGF) were investigated
Animal studies used the technique of co-grafting AM with pre-transected peripheral nerve (NGF source) and showed what?
Animal studies used the technique of co-grafting AM with pre-transected peripheral nerve (NGF source) and showed improvement in graft survival and functional recovery
Lopez-Lozano et al. (1999) reported that clinical studies report only modest improvement on Unified Parkinson’s Disease Rating Scale (UPDRS) scores in ‘on’ and ‘off’ phases with increased proportion when?
Clinical studies report only modest improvement on Unified Parkinson’s Disease Rating Scale (UPDRS) scores in ‘on’ and ‘off’ phases with increased proportion of time when dopaminergic medication is working, namely the ‘on; phase, with a corresponding reduction in the ‘off’ phase (Lopez-Lozano et al. 1999)
Clinical trials of direct NGF infusion to support AM autografts show what?
Clinical trials of direct NGF infusion to support AM autografts also show some benefit
What is the negative of AM tissue grafts?
High level of morbidity and mortality associated with the techniques involved in the obtainment and transplantation of AM tissue though
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