We have collected preliminary data from people who were recently diagnosed with Parkinson's disease (PD), which show that an enzyme called phosphodiesterase 10A (PDE-10A) is markedly decreased in brain areas related to movement. PDE-10A is involved in control of movement by protecting the survival of neurons in relevant brain areas and by adjusting the action of dopamine. Moreover, the PDE-10A enzyme also could be important in PD because the gene that controls PDE-10A expression is located very close to one of the genes responsible for genetic forms of PD (called PARK2).
In this study we will explore the hypothesis that loss of PDE-10A expression in brain areas related to movement is a very early phenomenon in the clinical course of PD.
We will assess PDE-10A in people with early, untreated PD using a brain scan called positron emission tomography (PET). We are also planning to compare the activity of PDE-10A with known deficits in PD such as the loss of dopamine transporter.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
We think that PDE-10A is affected very early in the process of the disease, possibly before the appearance of motor symptoms. If our study is successful, PDE-10A is an enzyme that could be targeted with drug therapy. If indeed there is a marked loss of PDE-10A enzyme early in the course of PD, then new treatments altering its function may be able to protect neurons that die because of the disease and, therefore, avoid problems with movement.
Next Steps for Development:
If our study is successful, we aim to carry these experiments also to people who are at risk for developing PD, and to symptomatic and asymptomatic carriers of the genes responsible for PD. We are also aiming to take steps toward testing new treatments targeting the PDE-10A enzyme.