Progressive Supranuclear Palsy

What Causes Progressive Supranuclear Palsy?

PSP is caused by deterioration of the parts of the brain that control movement and thought processes, most often the brain stem. Damage in one of these areas, the substantia nigra, is also associated with Parkinson’s disease, which may explain the similarities between the two disorders.

Scientists don’t know what causes brain degeneration in PSP, but research has shown that people with PSP have an accumulation of proteins called tau in their brains. Accumulations of tau protein have also been associated with Alzheimer’s disease and other degenerative brain diseases.

Is Progressive Supranuclear Palsy Hereditary?

In most cases, PSP does not seem to be inherited. Most people with PSP have no family history of the disorder. However, scientists have found an association between some PSP cases and abnormal changes (mutations) in the MAPT gene. This gene carries instructions for making tau protein. Mutations in the STX6, EIF2AK3, and MOBP genes have also been associated with PSP.

The link between these gene mutations and the disorder suggests a genetic component to PSP risk, even if it is not directly inherited. Scientists believe that an interplay of genetic predispositions and environmental factors likely cause PSP.

How Is Progressive Supranuclear Palsy Detected?

Early diagnosis of PSP is challenging because its symptoms so closely resemble those of Parkinson’s and several other neurological diseases. Both Parkinson’s and PSP most often occur after the age of 40 and exhibit many of the same movement-related symptoms. Therefore, PSP is often misdiagnosed as Parkinson’s in its early stages. However, the two disorders differ in some ways:

• Speech and swallowing problems are often more severe and occur earlier in PSP.
• Problems with eye control are less common in Parkinson’s.
• People with PSP usually have a rigid, upright stance, while people with Parkinson’s often lean forward.
• People with PSP typically don’t respond to medications that are effective at treating Parkinson’s.

How Is Progressive Supranuclear Palsy Diagnosed?

No test or exam can definitively detect PSP. A doctor may diagnose PSP after assessing the patient’s medical history and ruling out other potential causes of the symptoms. The diagnostic process may include:

• Physical exams and neurological exams to rule out other possible causes of the symptoms
• Magnetic resonance imaging (MRI) or positron emission tomography (PET) scans to look for brain degeneration in the parts of the brain associated with PSP

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Progressive Supranuclear Palsy Treated?

No treatment will stop the progression of PSP or reverse the effects of its symptoms. Most treatments aim to reduce the impact of symptoms, improve quality of life, and prevent life-threatening complications. Possible treatment options include:

• Some drugs used to treat Parkinson’s, such as levodopa, may minimally and temporarily ease movement symptoms in some cases.
• Botulinum toxin may help control involuntary eyelid movements.
• Antidepressants may relieve mood symptoms and may also help alleviate pain.

Other treatments and therapies include:

• Physical therapy
• Occupational therapy
• Corrective devices for vision impairment
• Mobility aids
• Deep brain stimulation (DBS)

How Does Progressive Supranuclear Palsy Progress?

PSP symptoms worsen rapidly, and most people with the disorder will suffer from severe impairments within 3-5 years after symptoms first appear. Long-term complications can include:

• Head injuries or bone fractures from falls
• Disrupted sleep
• Difficulty swallowing
• Respiratory infections such as pneumonia

Most people with PSP will not survive more than 6-9 years after the onset of symptoms. Pneumonia, often caused by inhaling food or liquids (aspiration), is the most common cause of death. However, more prolonged survival is possible if the risk of aspiration and choking is carefully managed.

How Is Progressive Supranuclear Palsy Prevented?

There is no known way to prevent PSP.

Progressive Supranuclear Palsy Caregiver Tips

• Educate yourself about the disease, its effects, and the side effects of medications used to treat it. People with PSP are also at higher risk of developing depression and anxiety. Be on the lookout for the warning signs of these conditions.
• Encourage a healthy lifestyle. There is no cure for PSP, but there are ways to manage symptoms and maintain a good quality of life for as long as possible. Facilitate your healthy eating habits and get as much exercise as possible.
• Join a support group for caregivers. Caregivers are at risk of developing physical and mental health issues, too. So take time for yourself, and get the help you need when you feel overwhelmed.

Many people with PSP also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with PSP:

• Some people with PSP also suffer from mild depression.
• Some people with PSP have a co-existing anxiety disorder.
• The majority of people with PSP exhibit symptoms of dementia.

Progressive Supranuclear Palsy Brain Science

Tau protein is normally present in brain cells, and it plays an essential role in the health and function of the cells. However, in PSP, tau takes on an abnormal form and destroys protein filaments in the cells. Scientists believe that the destruction of these filaments causes the cells to die.

Researchers don’t yet know what causes the accumulation of abnormal tau protein in the brains of people with PSP. Some theories include:

• An infectious agent causes an alteration of the protein, such as in prion diseases like Creutzfeldt-Jakob disease.
• Random genetic mutations cause the production of abnormal tau in specific cells.
• Exposure to an environmental toxin triggers the tau abnormality.
• Free radicals, molecules generated during normal metabolic processes, damage cells and set the tau accumulation process in motion.

Progressive Supranuclear Palsy Research

Title: Remote Monitoring in Progressive Supranuclear Palsy (PSP)

Stage: Not Yet Recruiting

Principal investigator: Anne-Marie A Wills, MD MPH

Massachusetts General Hospital

Boston, MA

This is a single-arm, longitudinal, observational study on the use of wearable sensors and digital health technology to measure fall frequency and motor, speech, and cognitive function in patients with PSP over approximately one year. Participants will perform supervised remote assessments monthly and in-person assessments every six months.

The primary objective of this study is to determine the feasibility of using wearable sensors and digital health technology to monitor patients with possible or probable PSP remotely.

Secondary objectives are to measure PSP progression using sensor-derived motor and tablet-derived speech and cognitive measures.

In brief, 40-50 individuals with possible or probable PSP will be enrolled at 4-5 sites in the U.S. and followed for one year. During the monitoring period (1 year), a wearable pendant sensor (PAMSys, BioSensics) will be used to monitor falls and physical activity (step counts) of all participants during activities of daily living (ADL). Each month, participants will have tele-video conferences with the sites to perform supervised gait and balance tasks while wearing 3 LEGSys (BioSensics) sensors. Participants will also perform cognitive tests using a study-supplied tablet, including fluency, color trails, and go-no-go tapping tests. In addition, participants will undergo more extensive testing every three months, including the PSPRS, MoCA, quality of life questionnaires, and functional rating scales performed remotely (virtually). Finally, at approximately six months, participants will undergo an in-person PSPRS (to coincide with their clinic appointments).

Title: A Phase 2a Study of TPN-101 in Patients With Progressive Supranuclear Palsy (PSP)

Stage: Not Yet Recruiting

Transposon Therapeutics

Westport, CT

This is a Phase 2a multi-center, randomized, double-blind, placebo-controlled parallel-group, 4-arm study with an open-label treatment phase in patients with PSP. This study includes a 6-week Screening Period, a 24-week Double-blind Treatment Period, a 24-week Open-label Treatment Period, and a Follow-up Visit 4 weeks post-treatment.

Title: Image Characteristic and Longitudinal Follow up of 18F-PMPBB3 (APN-1607) PET for Progressive Supranuclear Palsy

Stage: Not Yet Recruiting

Contact: Kun-Ju Lin

Chang Gung Memorial Hospital

Taoyuan City, Taiwan

The study will enroll 20 PSP and eight normal subjects with complete neurological examination, 18F-PMPBB3 (APN-1607) PET, and MRI assessment. To explore: (1) whether 18F-PMPBB3 (APN-1607) can detect the 4R tau protein in the brain of PSP patients; (2) whether 18F-PMPBB3 (APN-1607) can distinguish the clinical characteristics of PSP; (3) Whether the distribution of tau deposition is related to disease severity, progression, and prognosis.

Progressive supranuclear palsy (PSP), also known as Steele-Richardson-Olszewski syndrome, has a similar incidence in men and women. The pathophysiology of PSP remains unclear, but it is related to the abnormal accumulation of 4R tau protein in the brain. Recently, a new generation of novel radiotracer 18F-PMPBB3 (APN-1607), which can be labeled with 4R PHF-tau without significant off-target binding, has been successfully developed. The study will enroll 20 PSP and eight normal subjects with complete neurological examination, 18F-PMPBB3 (APN-1607) PET, and MRI assessment. To explore: (1) whether 18F-PMPBB3 (APN-1607) can detect the 4R tau protein in the brain of PSP patients; (2) whether 18F-PMPBB3 (APN-1607) can distinguish the clinical characteristics of PSP; (3) Whether the distribution of tau deposition is related to disease severity, progression, and prognosis. The research results will help us understand the potential of 18F-PMPBB3 (APN-1607) as a biomarker for diagnosis and therapeutic assessment tool for progressive nuclear paralysis and other tau proteinopathies.