Study Rationale:
CNM-Au8 is a new type of nanomedicine that consists of tiny crystals made of pure gold. The multifaceted surface of these gold nanocrystals provides a platform for metabolic reactions that can protect diseased nerve cells from death. Treatment with CNM-Au8 benefits many types of nerve cells, including the dopamine-producing neurons that are selectively eliminated in Parkinson’s disease (PD). To assess this protective activity, we exposed dopamine-producing neurons isolated from pre-clinical models to neurotoxins, and used neurotoxins to destroy the same neurons in the brains of pre-clinical models. In both cases, we found that treatment with CNM-Au8 increased the survival and function of these neurons. Now, we will determine whether the gold nanoparticles protect neurons by preventing the toxic accumulation of alpha-synuclein, a protein that contributes to neurodegeneration in PD.
Hypothesis:
We will test the hypothesis that CNM-Au8 prevents alpha-synuclein aggregation in the dopamine-producing nerve cells of people with Parkinson’s and in a pre-clinical model of PD.
Study Design:
Using genome engineering technology, we have generated neurons derived from cells isolated from people with Parkinson’s. We will expose these patient-derived neurons to toxic levels of alpha-synuclein to determine whether CNM-Au8 treatment can protect them from dying and enhance their energy-generating metabolic reactions. Next, we will determine whether CNM-Au8 can rescue motor function and protect dopamine-producing neurons in pre-clinical models that produce toxic levels of alpha-synuclein in their brains. These pre-clinical models will receive oral doses of CNM-Au8 or a placebo, and we will then monitor and compare their behavior, metabolite levels, and the survival of dopamine-producing neurons to determine the disease-modifying effects of the gold nanoparticles.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
By targeting metabolic reactions in neurons, CNM-Au8 provides a novel approach to treating PD. Positive results from these studies will reinforce the idea that improving the metabolic and bioenergetic capacity of the brain is a promising new strategy for the treatment of Parkinson’s disease, and will strongly support the clinical development of CNM-Au8 as a disease-modifying treatment.
Next Steps for Development:
These studies will support the rapid advancement of CNM-Au8 into a Phase II, randomized, placebo-controlled clinical trial for the assessment of its safety and efficacy at treating Parkinson’s disease.