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Progressive supranuclear palsy (PSP) is a rare brain disorder with no known cure. As it worsens, the disease can cause serious problems with walking, balance, eye movements, swallowing, as well as changes in mood and thinking.
A recent large-scale international study led by Krembil Senior Scientist Dr.
Gabor Kovacs identified the underlying stages of disease, which are key to better managing symptoms and developing targets for therapy.
"This is the first study that attempts to define stages of PSP," says Dr. Kovacs. "By knowing where to look, we can better monitor patients and better predict prognoses."
The research project included international collaborators, including Dr. John Trojanowski from the University of Pennsylvania and Dr. Günter Höglinger from the German Centre for Neurodegenerative Disease. Together, the research team evaluated more than 200 brains affected by PSP and defined six stages of disease progression.
An abnormal protein, known as the pathological tau protein, is seen in the brains of individuals with PSP. The researchers traced how this protein spreads through the brain in distinct paths for each clinical sub-type. The findings showed that irrespective of the disease's clinical sub-type the first stage of PSP develops in the same brain region.
"Knowing where the pathological accumulation of the tau protein starts in the brain, means that we can now focus on researching this area specifically," says Dr. Kovacs. "Because this region comprises unique cell populations with different receptors or metabolic activity — we will get a better idea of which brain cells to target with therapy in the early stages of PSP."
The study was also able to show that the major difference between clinical sub-types of PSP relates not only to the involvement of nerve cells but also to the supporting cells called astroglia and oligodendroglia.
"We've provided a conceptual framework for the spread of tau to understand the mechanisms of how pathological tau jumps from one neuron to the next neuron and how the supporting tissue plays a role," says Dr. Kovacs. "With this understanding, we hope to provide a foundation for basic research to develop blocking agents or therapies to stop the spread of the tau protein."
Dr. Kovacs is Co-Director of the Rossy Program for PSP research, which is led by Dr. Anthony Lang, Director of the Movement Disorders Clinic at Toronto Western Hospital. Funding for the study was obtained by Dr. Lang. Under the directorship of Dr. Lang and a team of world-leading researchers in movement disorders, it is the only program in Canada dedicated to PSP research and care. The research was also supported by Open Access funding from Projekt DEAL, the National Institutes of Health, the Penn Institute on Aging, Fundació Marató de TV3, the Rossy Foundation, the Edmond J. Safra Foundation, the Bishop Dr. Karl Golser Foundation, the German Research Foundation (DFG), the German Federal Ministry of Education and Research (BMBF), the NOMIS Foundation and the Toronto General & Western Hospital Foundation.