Progressive Supranuclear Palsy: Diagnostic Considerations and Emerging Treatment Approaches

Summary

This video discusses Progressive Supranuclear Palsy (PSP), a neurodegenerative disorder characterized by motor, cognitive, and behavioral symptoms. The classic form, Richardson syndrome, involves eye movement difficulties and gait instability. Though no FDA-approved treatments exist, symptomatic therapies such as levodopa, botulinum toxin injections, and intensive rehabilitation can help manage symptoms. Research is focused on tau-related therapies, including monoclonal antibodies and gene expression modulation, to slow disease progression. Despite the challenges, ongoing clinical trials and a deeper understanding of tau pathology offer hope for future disease-modifying treatments and a potential cure for PSP.

Takeaways

• 😀 PSP (Progressive Supranuclear Palsy) is a neurodegenerative disorder with no FDA-approved treatments, and it often leads to death, particularly in Richardson syndrome patients.
• 😀 Levodopa, commonly used in Parkinson's disease, may help some PSP patients, though the response is less pronounced than in Parkinson's disease.
• 😀 Some PSP patients with severe eyelid apraxia may benefit from botulinum toxin injections in the pre-tarsal muscles to assist with eye opening.
• 😀 Intensive physical, occupational, and speech therapy is considered the most beneficial symptomatic treatment for PSP, with significant improvements in the PSP rating scale shown in trials.
• 😀 Coenzyme Q-10 supplementation has shown some promise in small trials, but its benefits are inconclusive, and it's not FDA-approved for PSP.
• 😀 Experimental strategies are focused on modifying tau gene expression or preventing its toxic accumulation and spread in the brain.
• 😀 Tau accumulation in PSP may lead to a toxic gain-of-function, contributing to neurodegeneration and possibly spreading through prion-like mechanisms.
• 😀 Previous trials using drugs like Davina tide and TPI 287, which aimed to stabilize microtubules and compensate for loss of tau function, were not successful in slowing disease progression.
• 😀 Monoclonal antibodies targeting tau protein (e.g., viv 92 and ABBV-80-12) are undergoing Phase 2 clinical trials, with hopes to reduce tau toxicity and slow PSP progression.
• 😀 Current research focuses on reducing toxic tau forms and preventing their spread to neighboring neurons as a potential way to slow or stop PSP progression.
• 😀 The 2017 Movement Disorder Society's PSP diagnostic criteria expanded the clinical spectrum of PSP, recognizing various phenotypes, including nonfluent variant primary progressive aphasia and corticobasal syndrome.

Q & A

What is Progressive Supranuclear Palsy (PSP)?

Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder that affects motor control, cognition, and behavior. It is caused by the accumulation of abnormal tau protein in the brain, leading to issues such as eye movement difficulties, gait instability, and falls.

What is the main cause of neurodegeneration in PSP?

The current understanding is that neurodegeneration in PSP is primarily caused by toxic gain-of-function due to tau protein aggregation. This results in tau forming insoluble deposits that spread throughout the brain, potentially via a prion-like mechanism.

Are there any FDA-approved treatments for PSP?

Currently, there are no FDA-approved treatments for PSP. While there are symptomatic treatments, such as levodopa and botulinum toxin injections, these do not address the underlying disease progression.

What treatments are available to help manage PSP symptoms?

Some symptomatic treatments include levodopa (though less effective than in Parkinson's disease), botulinum toxin injections for eyelid apraxia, and intensive physical, occupational, and speech therapy. These therapies can help improve the quality of life, especially when provided in a structured and intensive manner.

How effective is physical therapy for PSP patients?

Intensive physical, occupational, and speech therapy has shown significant benefits for PSP patients. Clinical trials, such as the one in Italy, demonstrated improvements in the PSP rating scale, particularly with a month of intensive rehabilitation.

What is the role of Coenzyme Q10 in PSP treatment?

Coenzyme Q10 supplementation has been tested as a treatment for PSP, with a small trial showing modest benefits. However, larger trials, including a one-year study, did not replicate these benefits, indicating that Coenzyme Q10 may not be an effective disease-modifying treatment for PSP.

What are the major challenges in developing treatments for PSP?

The main challenge is the lack of understanding about the precise mechanisms underlying tau's toxic gain-of-function in PSP. Additionally, therapies targeting tau have shown mixed results in clinical trials, and no current treatment can slow disease progression.

What are monoclonal antibodies, and how are they being tested for PSP?

Monoclonal antibodies are laboratory-made molecules designed to bind to specific proteins. In PSP, monoclonal antibodies targeting tau proteins, such as viv 92 and ABBV 80 12, are being tested in Phase 2 clinical trials to assess whether they can reduce tau aggregation and slow disease progression.

What are the variant presentations of PSP according to the 2017 Movement Disorder Society diagnostic criteria?

The 2017 diagnostic criteria expanded the clinical spectrum of PSP to include variant presentations, such as nonfluent variant primary progressive aphasia and corticobasal syndrome, in addition to the classic Richardson syndrome.

What is the prognosis for patients diagnosed with Richardson syndrome?

Patients with Richardson syndrome, a severe form of PSP, typically experience significant disability, including eye movement problems and severe gait instability. Unfortunately, most patients with PSP, particularly Richardson syndrome, will die from the disease over time due to its progressive nature.