Properly scaled and targeted AAV2-NRTN (neurturin) to the substantia nigra is safe, effective and causes no weight loss: Support for nigral targeting in Parkinson's disease

► Very high doses of AAV2-NRTN can be safely administered to the substantia nigra (SN), causing no toxicity. ► For translational purposes, a wide 'therapeutic index' exists, for very low doses provide neuroprotection. ► The effect on body weight reported by others as 'dangerous' requires a very high dose of vector. ► The high vector dose that affects body weight does so via significant mistargeted (non-SN) protein. ► Data support targeting the substantia nigra with AAV-NRTN in Parkinson's patients to maximize neurotrophic response.