Objective/Rationale:
Inflammation in the brain is one of the causes of Parkinson’s disease. XPro1595 is a selective inhibitor of soluble TNF that “turns off” inflammation to stop the loss of dopaminergic neurons and the prevent disease progression. Previous studies with XPro1595 have delivered the drug directly to the brain with a catheter. This study will determine of XPro1595 can be effective when given as a subcutaneous injection. If the subcutaneous delivery is effective, patients can be treated without needing surgery.
Project Description:
The 6-OHDA pre-clinical model remains the “gold standard” pre-clinical model for testing drug candidates which may afford therapeutic benefit in Parkinson’s disease. In this model, a neurotoxin is injected into the part of the brain where the dopamine-producing are located. When the dopamine-producing cells die, the model develops PD-like symptoms. When the models are treated withXpro1595 to determine if the PD-like symptoms go away.
In this study, models will be treated with XPro1595 twice a week with subcutaneous injections early or late after the lesion (3 or 14 days). Two drug doses will be tested (10mg/kg and 50mg/kg). A control group will get no treatment. For about a month, the models get behavioral testing to determine if XPro1595 is preventing locomotor deficits resulting from the 6-OHDA lesion. After the study period, biochemical, histologic and immunologic studies are performed to determine the effects of the XPro1595 on neuroinflammation,dopaminergic cells in the substantia nigra and the immune system.
These studies will be performed by Malu Tansey’s team at Emory University in Atlanta, Geogia.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The design of the study is simple, but the information will be important. We know that XPro1595 prevents disease progression when delivered directly to the substantia nigra via a catheter. This type of drug delivery requires surgery. If the experiment demonstrates that peripheral delivery of XPro1595 (by subcutaneous delivery) is effective, patients will be able to avoid the surgery associated with placement of the catheter.
Anticipated Outcome:
The results of this study will dictate how XPro1595 is used to treat patients with Parkinson’s disease. If peripheral administration shows the drug to be effective in preventing PD-like symptoms in the models, this is the drug delivery strategy that will be used in the clinical trials. If the peripheral administration is not effective, then the clinical trials will be performed with direct infusion of XPro1595 into the substantia nigra.
PARTNERING PROGRAM
This grant was selected by The Michael J. Fox Foundation staff to be highlighted via the Foundation’s Partnering Program.
