A primer on progressive supranuclear palsy

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Progressive supranuclear palsy (PSP) is a brain disease similar to Parkinson’s disease in its outward appearance but to Alzheimer’s disease under the microscope. It has no known effective treatment or cure. PSP affects brain cells that control walking, balance, mobility, vision, speech, swallowing, thinking and behavior. Symptoms begin, on average, at age 63 but in a few cases as early as the 40s. It is slightly more common in men than women and slightly more common in those with lesser education.

Five to six people per 100,000 have PSP, similar to the figure for Lou Gehrig’s disease but only about three per cent of the figure for Parkinson’s disease. Only a third of those with PSP have received the correct diagnosis.

The most common first symptom, occurring on average in the 60’s, is loss of balance while walking, usually with unexplained falls. A sizable minority will start with a milder gait problem that resembles the stiff, slow walk of Parkinson’s. Sometimes the falls are described as attacks of “dizziness,” prompting testing for problems of the inner ear, the heart or the blood vessels of the brain.

Other common early symptoms are forgetfulness and changes in personality. The latter can take the form of a loss of interest in ordinary pleasurable activities or increased irritability. Less common early symptoms are general slowing, trouble with eyesight, slurring of speech, and mild shaking of the hands. Difficulty driving a car is common early in the course of PSP.

The term “progressive” was included in the name of the disease because, unfortunately, the early symptoms worsen and new ones develop sooner or later. After five to six years, on average, the imbalance and stiffness make walking very difficult or impossible. The difficulty with organizing thoughts and speech makes communication difficult. If trouble with eyesight was not present early on, it eventually develops in almost all cases and can sometimes be as disabling as the movement difficulty.

Difficulty with swallowing develops eventually in most patients. Usually, trouble with thin liquids precedes difficulty with solid food. This is because in PSP, the swallowing muscles have difficulty creating a watertight seal separating the path to the stomach from the path to the lungs. Repeated subtle aspiration can cause pneumonia and ‘aspiration pneumonia,’ in fact, is the most common cause of death in PSP.

Neurologists manage the symptoms of PSP in a superficial way with drugs for Parkinson’s disease and other PSP symptoms such as insomnia, impaired memory, depression and bladder urgency. Physical therapy for gait and swallowing therapy are also useful. Sometimes special glasses called prisms can help the eye movement problem to a degree and botulinum toxin (“Botox”) injections can help the abnormal eyelid closure that affects a few PSP sufferers.

A real prevention or halting of the progression of PSP will require more knowledge about its real cause. The degenerating brain cells have an abnormal accumulation of a normal protein called “tau.” These clumps of tau are called “neurofibrillary tangles.” We don’t know whether the problem is that the tau is defective from the time of its manufacture, or if it is damaged later, or if it is merely produced in excess. It is increasingly likely that at least one important part of the cause of the misbehaviour of the tau protein is some combination of genetic defects that alter the manufacture of tau or control its degradation by the brain cell’s “garbage disposal” machinery.  Another important factor is the unfortunate ability of damaged tau protein to produce identical damage in previously normal copies of the tau protein in a chain reaction spreading the tau abnormality through the brain.

All of these abnormal processes in the brain cells in PSP offer opportunities to scientists to develop drugs or other therapies that can act as a “monkey wrench” to disrupt one of the many vulnerable points in this complicated disease process. In fact, several such treatments have been tested recently and several others are near the stage of human trials. CurePSP’s research program is aimed at developing such treatments. Fortunately, the similarity of the tau protein problem in PSP to that in Alzheimer’s disease means that the huge worldwide research effort to eradicate AD could provide the same benefit to people with PSP.  This is what we’re hoping for – as CurePSP’s motto says, “Because Hope Matters.”