Progressive supranuclear palsy (PSP) is a mysterious and deadly neurological disorder that is usually not diagnosed until the patient dies and an autopsy is performed. However, researchers at the University of California, San Francisco, have now found a way to identify this condition while patients are still alive.

A study published in the journal Neurology on July 3rd revealed a pattern in the cerebrospinal fluid of patients with PSP, using new high-throughput technology that can measure thousands of proteins in a small drop of fluid.

Researchers hope that protein biomarkers will lead to the development of a diagnostic test and targeted therapies that could halt the deadly course of the disease.

The disorder became known to the public 25 years ago when Dudley Moore, star of the movies "10" and "Arthur," shared his diagnosis of PSP. It is often mistaken for Parkinson's disease, but PSP progresses faster, and patients do not respond to Parkinson's disease treatments. Most patients with PSP die within seven years of the onset of symptoms.

Diagnosis is crucial because treatments work best in the early stages
PSP is believed to be caused by the accumulation of tau proteins that cause the weakening and death of cells. It is a type of frontotemporal dementia (FTD) that affects cognition, movement, and behavior. Its characteristic symptoms include poor balance with frequent backward falls and difficulty moving the eyes up and down.

“Unlike Alzheimer's disease, there are no tau scans, blood tests, or MRIs that provide a definitive diagnosis of PSP. For many patients, the disease goes unnoticed,” said Julio Rojas, MD, PhD, from the Department of Neurology, the Memory and Aging Center, and the Weill Institute for Neurosciences at UCSF.

“When new drugs are approved for PSP, the best chance for patients will be to receive treatment in the earliest stage of the disease when it is most likely to be effective,” he said.

The inability to identify PSP has hindered the development of new treatments, according to the study's co-authors Adam Boxer, MD, PhD, professor of memory and aging in the Department of Neurology at UCSF and director of the Alzheimer's Disease and Frontotemporal Dementia Clinical Trials Program.

Proteins associated with neurodegeneration
Researchers measured protein biomarkers using high-throughput technology for protein analysis, which is based on molecules that bind to proteins with high selectivity and specificity.

The study included 136 participants, with an average age of 70 years, and involved patients from UCSF and other institutions with symptoms consistent with PSP, as well as autopsy-confirmed cases of PSP. Scientists compared biomarkers from these cases with living patients, as well as with healthy participants and patients with other forms of FTD.

Researchers found lower levels of most proteins in those with confirmed or suspected PSP compared to healthy participants in the study. The protein signature of confirmed cases of PSP also differed from cases of other forms of FTD, as well as from living patients.

All those with confirmed or suspected PSP had higher levels of proteins associated with neurodegeneration. Researchers also found some inflammatory proteins that correlated with disease severity and reduced proteins relevant to several critical brain cell functions that could be manipulated by future therapies.

“This work aims to create a framework for using these newly discovered proteins in future clinical trials,” said Amy Wise, the study's first author, formerly from the Department of Neurology at UCSF and the Memory and Aging Center, and currently a medical student at UC Davis. “We hope to reach a point where a single biomarker, or a panel of biomarkers from a blood test or lumbar puncture, can provide definitive diagnostic and prognostic results for PSP.”

Source: University of California