Diagnostic and drug screening for molecular signatures of early onset sporadic parkinson's disease

A method of screening one or more test compounds for treating early onset sporadic Parkinson's Disease, the method comprising:

• contacting a quantity of midbrain dopaminergic neurons differentiated from early onset sporadic Parkinson's Disease patient blood cell-derived induced pluripotent stem cells (iPSCs) with the one or more test compounds;
• measuring a-synuclein protein levels and PKCα phosphorylation levels in the contacted midbrain dopaminergic neurons;
• and
• selecting one or more of the test compounds as a compound or compounds for treatment of early onset sporadic Parkinson's Disease based on the measured a-synuclein protein levels and PKCα phosphorylation levels, the selected one or more compounds being able to reduce α-synuclein protein levels and PKCα phosphorylation levels in the midbrain dopaminergic neurons, compared to α-synuclein protein levels and PKCα phosphorylation levels in the dopaminergic neurons not contacted with the selected one or more compounds,
• wherein the iPSCs are produced from early onset sporadic Parkinson's Disease patients who are younger than 50 years old with no reported family history of Parkinson's Disease,
• wherein the midbrain dopaminergic neurons express higher levels of α-synuclein and phosphorylated PKC-α compared to controls derived from healthy subjects.