Redefining Parkinson’s disease

Science, technology, and passion are converging to alter the future of neurodegenerative disease

Neurodegenerative diseases have traditionally been defined by their clinical manifestation. For example, the diagnosis of Alzheimer’s disease was based on memory loss and Parkinson’s disease on slowness of movements. But in recent years, a significant evolution in our biomarker tools has allowed us to investigate the causes of these diseases and diagnose better, classify, and even treat patients with these disorders. “We’re on the verge of a revolution in neurodegenerative disease,” says Gennaro Pagano, Group Leader and Expert Medical Director within Roche Pharma Research and Early Development (pRED) Neuroscience & Rare Diseases.

Scientists now understand that amyloid plaques - clumps of aggregated beta-amyloid protein - play an important detrimental role in Alzheimer’s disease. Today, it is possible to measure these plaques in patients’ brains while they are still alive. In a similar way, the formation of clusters of misfolded alpha-synuclein - a presynaptic neuronal protein - appears to be a key driver of Parkinson’s disease progression. However, it is also involved in other diseases such as Lewy body dementia and in people suffering from Alzheimer’s disease. This new understanding, coupled with the recent ability to monitor aggregates of this disease-related protein in patients, has led the field, including scientists at Roche, to call for a novel definition of these disorders for research purposes: as a unified Neuronal Synuclein Disease (NSD). 

By identifying this common feature across diseases that traditionally have been treated separately, the number of patients who stand to potentially gain from this discovery expands by about fivefold. Ultimately, it will be a way to identify the individuals who will benefit the most from these therapies.

Rethinking Parkinson’s disease in this way is just one way that Roche is taking the lead on envisioning a new future for people living with this disease. Although alpha-synuclein is an important driver of disease onset and progression, and has long been an area of interest for Roche, it’s not the only one. Other factors such as inflammation are also involved in the progression of the disease, impacting the worsening symptoms and merit their own therapeutic approaches. “We believe there won’t be a single silver bullet for this disease,” says Patrik Brundin, Therapeutic Area Leader for Movement Disorders within pRED Neuroscience & Rare Diseases. “Each patient will likely require a different mix of medicines at different stages of their disease, and with more options available, this precision medicine becomes possible.” For example, medicines that now work for controlling already manifested movement symptoms, such as the symptomatic drug L-DOPA, could be combined with medicines that aim to slow or halt disease progression.

By exploring different targets and different kinds of medicines to address those targets, Roche seeks to develop a suite of treatments for patients. “We are targeting Parkinson’s disease from many different angles, with a unique combination of strategy, science, and vision,” says Gennaro. “I’m proud to be at Roche because we have the right tools, the right people, and the right commitment to stop this disease.”

In the long term, Patrik, Gennaro, and their Roche colleagues are excited about an even bigger opportunity beyond managing symptoms and slowing or stopping disease progression: the potential of preventing Parkinson’s disease from starting in the first place. Scientists now know that abnormal alpha-synuclein is present in millions of people without any symptoms — and only roughly a third of these people are estimated to develop symptoms in their lifetime. What if disease progression could be stopped in these people before death of neurons even started?

It may sound like science fiction, but this approach is already being taken in cardiovascular disease, where people are treated with cholesterol-lowering medicines like statins to prevent heart attacks and strokes, Gennaro and Patrik pointed out. As Roche scientists and their collaborators across industry, academia, philanthropy, and regulatory bodies continue to advance the science, Gennaro thinks that one day, future generations might be able to say, “there used to be a disease called Parkinson’s.”

Overall, the outlook for patients and their families is much more optimistic than when Patrik’s own father was diagnosed with Parkinson’s disease 50 years ago, says Patrik. “Gennaro likes to say he’ll stop when Parkinson’s stops,” he added. “I think that will be possible in his lifetime.”

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