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

Parkinson's disease, formerly known as shaking palsy, is the second most common neurodegenerative disease in Germany after Alzheimer's disease. It affects about 400,000 people in Germany alone and can neither be cured nor can its progression be slowed down. Approximately 90% of patients suffer from the idiopathic form of the disease, the molecular causes of which are poorly understood. This is probably one reason why there is still no causal therapy for this disease, only a symptomatic one.

17.08.2022

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.

Press release HZM

 


Neue Erkenntnisse aus der Parkinsonforschung: Hemmung der SHH-Signaltransduktion als möglicher früher Behandlungsansatz

In einem interdisziplinären Ansatz haben Helmholtz Munich Forschende mit SyNergy-Mitgliedern Fabian Theis und Wolfgang Wurst in Kooperation mit weiteren Parkinsonforschern menschliche Zellen, die aus Parkinson Patient:innen gewonnen wurden, dazu genutzt, ein zelluläres Modell des frühen Parkinson zu etablieren. Die Analyse dieses zellulären Modells mittels Einzelzell-RNA-Sequenzierung und der anschließenden Validierung ergab Erstaunliches...

Bereits in diesem frühen Modell des idiopathischen Parkinsons liegt eine Fehlfunktion der Mitochondrien vor. Hinzu kommt die abnorme Ausprägung von primären Zilien, einem Zellorganell, das für die Interaktion der Zelle mit seiner Umgebung verantwortlich ist. Beide krankheitsassoziierten Phänotypen können durch die Inhibition der SHH-Signaltransduktion normalisiert werden.

Pressemitteilung HZM