New Insights From Parkinson’s Research - Inhibition of Shh Signal Transduction as a Possible Early Treatment Approach

In addition, Parkinson's disease develops insidiously and often goes unnoticed for decades. When the tremors and muscle stiffness typical of the disease begin, a large number of nerve cells have already been destroyed. The failure to date of disease-modifying interventions in Parkinson's disease may be due in part to the fact that the pathology in established Parkinson's disease is too advanced for the appropriate treatments to be effective, or that the early "unnoticed" pathology is different from the advanced one.

In an interdisciplinary approach, Helmholtz Munich researchers with SyNergy members Fabian Theis and Wolfgang Wurst, in cooperation with other Parkinson's researchers, have used human cells obtained from Parkinson's patients to establish a cellular model of early Parkinson's disease. The analysis of this cellular model through single-cell RNA sequencing and the subsequent validation revealed astonishing results. Already in this early model of idiopathic Parkinson's disease, there is a malfunction of the mitochondria. In addition, there is the abnormal expression of primary cilia, a cell organelle responsible for the interaction of the cell with its environment. Both disease-associated phenotypes can be normalized by inhibiting SHH signal transduction.