Promising Outcomes of Original Grant:
In preliminary development work, we demonstrated the capacity of the protein progranulin to protect against disease development in several pre-clinical model systems of human neurodegenerative diseases, namely, motor neuron disease, Alzheimer’s disease and PD. In recently completed MJFF supported work, we extended our original observations and have demonstrated compelling evidence of neuroprotection afforded by progranulin pretreatment in a sub-acute pre-clinical model of PD. In this work, both behavioral and neuropathological indices of CNS health were maintained in progranulin pretreated models when they were exposed to the Parkinsonism inducing agent MPTP.
Objectives for Supplemental Investigation:
Here we propose to test the more clinically relevant treatment scenario of intervening with progranulin therapy after disease has been established, in a progressive pre-clinical model of Parkinson’s disease, a so called ‘delayed start’ intervention. We will again assess both behavioral and neuropathological indices of CNS health in pre-clinical models in which we will induce a PD-like disease over a period of 5 weeks. Once disease has been established we will treat the mode with progranulin and determine whether disease progression can be halted or blunted by the treatment
Importance of This Research for the Development of a New PD Therapy
The assessment of disease outcome using this more clinically relevant time of intervention is the critical next step in the development path of progranulin as a therapy for PD. A successful outcome here will give us greater confidence of progranulin’s potential utility in the clinical setting of PD.
This grant was selected by The Michael J. Fox Foundation staff to be highlighted via the Foundation’s Partnering Program.