老司机直播

'Not all disease is the same': 老司机直播 study highlights protein variability in neurodegenerative diseases

Portrait of Joel Watts
鈥淚f you鈥檙e developing therapies for Parkinson鈥檚 disease, and you鈥檙e targeting this alpha-synuclein aggregate pathology, it鈥檚 likely that one therapy may not fit all,鈥 says 老司机直播 Assistant Professor Joel Watts (photo by Gabrielle Giroday)

A new University of Toronto study sheds light on how protein strains vary in the brains of those affected by progressive neurodegenerative diseases like Parkinson鈥檚, suggesting the need for patient-specific medicines.

Their research findings, have important implications for people who are affected by progressive neurodegenerative diseases, and those trying to develop drugs to help them.

鈥淚t鈥檚 very evident in these diseases that there鈥檚 patient-to-patient variability. This provides a potential explanation of why,鈥 says Joel Watts, an assistant professor in the Faculty of Medicine鈥檚 department of biochemistry and a principal investigator at the Tanz Centre for Research in Neurodegenerative Diseases.

鈥淚 think it also really gets to the concept of patient-specific medicine that might be necessary. This research also suggests a way of how that could be done.鈥 

The research looked at the behaviour of different strains of the protein known as alpha-synuclein in the brains of mice. Alpha-synuclein is the principal pathological hallmark of Parkinson鈥檚 disease, and the research looked at whether different strains of the protein could lead to the manifestation of different diseases.

For the research, Watts and his team created two different strains of alpha-synuclein that were structurally different in test tubes. They then introduced them into mice and watched what happened.

The differing structures of the artificial strains led to different results, he says.

鈥淲hat we found was that they caused two completely different types of diseases,鈥 he says. 鈥淭he mice took different amounts of time to show symptoms of diseases [and] the symptoms of the disease were different for the two. The pathological markers of disease 鈥 these protein aggregates 鈥 were found in different brain regions. That鈥檚 exactly what you see in human disease.鈥

Watts says the findings illuminate the complexity of the disease.

They also demonstrate the need for patient-specific medicine, he says.

鈥淭he lesson from the research is that if you鈥檙e developing therapies for Parkinson鈥檚 disease, and you鈥檙e targeting this alpha-synuclein aggregate pathology, it鈥檚 likely that one therapy may not fit all. If there are differences, you may need to have patient-specific therapies,鈥 he says.

Watts has a background looking at prion diseases like mad cow disease.

He used his experience to inform his latest research, though he notes that, unlike prion diseases, neurodegenerative diseases such as Parkinson鈥檚 or Alzheimer鈥檚 are not infectious.

鈥淧rion diseases are not all the same. They are sometimes transmissible from animals to humans and, in rare cases, humans to humans. There are different varieties and they鈥檙e caused by different strains of prions,鈥 says Watts.

He also points to the flu, which requires people to get new flu shots every year due to varying strains.

鈥淭he same thing happens in neurodegenerative diseases. Instead of having changes in the viral DNA, you have changes in structure of these protein aggregates 鈥 these clumps of proteins that are pathological and found in the brains of people with diseases like Parkinson鈥檚 and Alzheimer鈥檚,鈥 he says.

Ultimately, the goal of Watts鈥檚 research is to develop testing paradigms for drugs that better reflect the complexity and variability of humans.

鈥淣ot all disease is the same and there is variability 鈥 and this could be explained by having different strains of alpha-synuclein,鈥 says Watts. 鈥淲e may need to consider patient-specific medicine when designing therapies or clinical trials to better classify patients into groups based on the type of strain they have.鈥

The study received support from the Canadian Institutes of Health Research, the Royal Society and European Research Council, among others. 

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