A specific hereditary form of Parkinson’s disease has long been regarded as a completely different condition from the most widespread type, which accounts for 85–90% of all Parkinson’s cases. This genetic variant is caused by mutations in a specific gene known as PARK2 and typically manifests unusually early, often before the age of 40. The progression of the disease is also different: it generally develops more slowly and is not characterised by the typical symptoms, such as constipation, sleep disturbances, and early signs of dementia, which are commonly associated with Parkinson’s disease.

Danish study finds signs of crucial protein
Until now, it has been assumed that this form of Parkinson’s does not involve the characteristic protein accumulations – known as Lewy bodies – which are otherwise observed in the classic form of the disease. This has made it difficult to understand the mechanisms behind the illness, and therefore also to develop targeted treatments for this specific patient group.

However, a new Danish study is now challenging that view.

A collaboration between Professor Poul Henning Jensen’s group at DANDRITE and Department of Biomedicine and Professor Morten Meyer’s group at the University of Southern Denmark (SDU) has found indications that the protein alpha-synuclein – the primary cause of Lewy body formation – also plays an active role in PARK2-related Parkinson’s. This finding could have direct implications for both diagnosis and treatment.

“Our results suggest that the genetic form of Parkinson’s is not as different from the classic type as we previously believed,” explains Professor Poul Henning Jensen. “This opens up the possibility that this group of patients may benefit from treatments targeting the accumulation of alpha-synuclein, which is thought to damage nerve cells.”

Hope for targeted diagnosis and treatment
Today, a number of drugs and therapies are being developed specifically to prevent damage caused by alpha-synuclein, but patients with PARK2 mutations have often been excluded from these trials, as it was not believed that the protein was involved in their condition.

The study thus contributes to breaking down the divide between genetic and so-called sporadic forms of Parkinson’s – and offers hope for better and more targeted treatment for patients who have previously been overlooked.

“If our findings can be confirmed in human brain tissue, it would suggest that Parkinson’s patients with a PARK2 gene mutation may benefit from the new treatments targeting alpha-synuclein, which are currently being tested in clinical trials,” says Poul Henning Jensen.

The study has recently been published in NPJ Parkinson’s disease.

Behind the study:

• The studies were conducted in prof Morten Meyers group by PhD student Sissel Ida Schmidt from Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
• PhD Emil Gregersen, Postdoc Hjalte Gram and Professor Poul Henning Jensen contributed to the analyses of alpha-synuclein.

External funding:

• The Jensen groups contribution to the study was supported by the Lundbeck foundation grants to Dandrite and the Collaborative project ERDYS

Impartiality issues

• No impartiality issues

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