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In a significant medical breakthrough, researchers at UC San Francisco have discovered a method to diagnose Progressive Supranuclear Palsy (PSP), a rare and fatal neurological disorder, while patients are still alive. Previously, PSP was typically diagnosed only posthumously through autopsy. This advancement could pave the way for earlier treatment interventions and improved patient outcomes.
The findings, published in the journal Neurology on July 3, reveal a distinct pattern of protein biomarkers in the spinal fluid of PSP patients. Using cutting-edge high-throughput technology, scientists measured thousands of proteins from a minuscule drop of fluid, identifying biomarkers that may lead to the development of a definitive diagnostic test and targeted therapies to slow the disease’s progression.
PSP first garnered widespread attention 25 years ago when actor Dudley Moore revealed his diagnosis. Often mistaken for Parkinson’s disease due to similar symptoms, PSP is distinct in its rapid progression and lack of response to Parkinson’s treatments. Most patients with PSP succumb to the disease within seven years of symptom onset.
Diagnosis and Early Treatment: A Crucial Link
PSP, a type of frontotemporal dementia (FTD), is thought to be triggered by the accumulation of tau proteins, which result in cellular weakening and death. This disorder impacts cognition, movement, and behavior, with hallmark symptoms including 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 Dr. Julio Rojas, co-senior author of the study, from the UCSF Department of Neurology, Memory and Aging Center, and the Weill Institute for Neurosciences.
Early diagnosis is critical as treatments are most effective during the initial stages of the disease. The inability to identify PSP has been a significant barrier to developing new treatments, according to Dr. Adam Boxer, co-senior author and director of the Alzheimer’s Disease and Frontotemporal Dementia Clinical Trials Program at UCSF.
“Previous research highlighted the potential of several non-specific neurodegeneration biomarkers for PSP, but they lacked sensitivity and specificity, especially during the early stages of the disease,” Dr. Boxer explained.
A New Diagnostic Approach
The study involved 136 participants with an average age of 70, including patients with symptoms consistent with PSP, autopsy-confirmed PSP cases, and healthy participants. By comparing protein biomarkers across these groups, researchers found lower levels of most proteins in those with confirmed or suspected PSP compared to healthy participants. Additionally, the protein signature in autopsy-confirmed PSP cases differed from those with other forms of FTD.
All participants with confirmed or suspected PSP exhibited higher levels of proteins associated with neurodegeneration. Researchers also identified inflammatory proteins correlating with disease severity and reduced proteins vital for brain cell function, which could be targeted in future therapies.
“This work aims to create a framework for using these newly identified proteins in future clinical trials,” said Amy Wise, the study’s first author and 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.”
Future Implications
The discovery of these protein biomarkers represents a monumental step toward developing diagnostic tests and treatments for PSP. Researchers are optimistic that these findings will lead to new clinical trials and, eventually, therapies that could significantly improve the quality of life for PSP patients.
The study received funding from various sources, including the NIH, the Rainwater Charitable Foundation, and the Alzheimer’s Drug Discovery Foundation, highlighting the broad support for advancing research in this area.
As the scientific community continues to explore the potential of these biomarkers, the hope is that PSP, once an elusive and deadly disorder, will become a condition that can be effectively managed and treated from its earliest stages.
