Iron and oxygen in PSP

Linking iron homeostasis to vulnerability patterns in Progressive Supranuclear Palsy

Gabor Kovacs
Tanz Centre for Research in Neurodegenerative Disease & Rossy Progressive Supranuclear Palsy Centre, University of Toronto
Pilot Project Grant
$50,000 over 1 year

About 10-15 percent of people who seek treatment at a Parkinson’s disease clinic have a rarer but more deadly disease – Progressive Supranuclear Palsy, or PSP.

Like Parkinson’s, PSP is a brain disorder that results in difficulties with walking and balance. People with PSP also experience problems with eye movements, swallowing, and with mood and thinking. Their life expectancy is usually shorter than that of people with Parkinson’s, and therapies to treat Parkinson’s are less effective with PSP.

Unlike Parkinson’s, in PSP researchers believe a protein called tau goes awry and accumulates in brain cells, ultimately killing them. In Parkinson’s, the suspect protein is alpha-synuclein.

“We really want to catch this disease even before the clinical symptoms start.”

At the University of Toronto, Dr. Gabor Kovacs, a neurologist and researcher, has joined a team of researchers focused on PSP. He’s investigating the accumulation of iron in cells in the region of the brain where PSP originates. Kovacs is studying the way these cells metabolize iron and oxygen, and their relationship to the tau protein and other iron-transporting proteins.

“Our aim is to find the first steps leading to disease, because then we have a strategy to prevent or develop a therapy target,” Kovacs says.

Kovacs and his colleagues are studying two forms of iron found in the cells of people who have donated their brains for research after their death. They are also evaluating a cluster of proteins, including the tau protein, to see how they regulate iron and interact with oxygen.

If Kovacs can determine which form of iron leads to the death of specific brain cells implicated in PSP, that knowledge could lead to a new drug or therapy to block the process early in the disease.

“We really want to catch this disease even before the clinical symptoms start,” Kovacs says.

Kovacs left his home in Vienna to work with Dr. Anthony Lang at the Rossy Progressive Supranuclear Palsy Centre because of its unique focus on PSP. The son and grandson of doctors, he grew up in Hungary and was drawn to neurology because of his interest in the human brain.

PSP is a particularly challenging disease for people and their families because of the swiftness with which it progresses, Kovacs says. In addition to opening an avenue for a new drug target, his research might also lead to a diagnostic tool.

Kovacs hopes his work will ultimately help people with PSP stay healthier longer.

“If we could expand the time when they were in a good condition, that would also mean a lot for families,” he says.

How your support made this research project possible

The development of multiple vaccines for COVID-19 has demonstrated the importance of building up a critical mass of researchers focused on a common goal. That’s Dr. Gabor Kovacs’s wish for Parkinson’s disease and PSP – and it’s the reason he says funding for research into these progressive brain disorders is so crucial.

“If we can collect and build up a critical mass of researchers with enough funding, then everything can be much faster and more effective,” he says.
Researchers need a collaborative and harmonized way to work,” says Kovacs.

Building up these well-funded research collectives could result in advances in Parkinson’s disease and PSP that would take months or years, rather than decades.

But at the moment, “we still don’t have the bulk of funding and researchers who could make results that could dramatically improve patients’ life expectancy or symptom-free phases,” he says.

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