Subject(s)
Data Collection/methods , Huntington Disease , International Cooperation , Registries , Europe , HumansABSTRACT
The lack of disease-modifying treatments currently available for not just some but most neurodegenerative diseases, including Parkinson's disease, Huntington's disease, and even stroke, helps explain increasing interest in cell-based therapies. One key aim of such treatment is to replace neurons or glia lost as a result of the disease, with a view to the cells integrating functionally within the host tissue in order to reconstruct neural circuitry. Clinical trials using primary human fetal tissue as a cell source commenced in Parkinson's disease (PD) in the 1980s; currently, comparable neural transplantation trials in Huntington's disease are underway. Disappointing results of later controlled trials in PD illustrated not least the vital importance of methodological issues relating to the structure and implementation of clinical trials, and these issues will be considered here in more depth.
Subject(s)
Clinical Trials as Topic , Neurodegenerative Diseases/therapy , Stem Cell Transplantation , Cell- and Tissue-Based Therapy/ethics , Cell- and Tissue-Based Therapy/methods , Cell- and Tissue-Based Therapy/standards , Clinical Trials as Topic/ethics , Clinical Trials as Topic/methods , Clinical Trials as Topic/standards , European Union , Humans , Neurodegenerative Diseases/pathology , Stem Cell Transplantation/methods , Stem Cells/physiology , Treatment OutcomeABSTRACT
Huntington's disease is one of a group of hereditary neurodegenerative diseases characterized by a glutamine expansion (polyQ) in proteins which are expressed in various cell populations. In agreement with this widespread distribution, we have previously shown that A(2A) receptor signaling is affected in mouse brain as well as in peripheral blood cells from a small cohort of HD patients. Here we analyzed a total of 252 subjects, including 126 HD gene-positive individuals, from different clinical sites. Consistent with our previous data we show that A(2A) receptor B(max) values are robustly increased at all HD stages as well as in 32 pre-symptomatic subjects. We report that the same abnormality is present also in other polyQ but not in non-polyQ inherited neurological disorders. Finally, we demonstrate that the same peripheral cells exhibit an altered membrane fluidity, a finding that may explain the observed change in receptor density. We argue that the observed alteration in lymphocytes reflects the presence of the mutant protein, and we suggest that the measure of the A(2A) receptor binding activity might be of potential interest for a peripheral assessment of chemicals capable of interfering with the immediate toxic effects of the mutation.
