ICBI UPDATE ON THE ROAD TO THE CURE - What is progressive supranuclear palsy?

What is progressive supranuclear palsy? Progressive supranuclear palsy (PSP) is a rare brain disorder that affects movement, control of balance, speech, swallowing, vision, mood and behavior, and thinking. The most common first symptom of PSP is a loss of balance while walking. Individuals may have unexplained falls or stiffness and awkwardness in gait. As the disease progresses, most people will begin to develop a blurring of vision and problems controlling eye movement. In fact, eye problems, in particular slowness of eye movements, usually offer the first definitive clue that PSP is the proper diagnosis. Individuals affected by PSP especially have trouble voluntarily shifting their gaze vertically (i.e., downward and upward) and also can have trouble controlling their eyelids, leading to a need to move the head to look in different directions, involuntary closing of the eyes, prolonged or infrequent blinking, or difficulty in opening the eyes. Another common visual problem is an inability to maintain eye contact during a conversation which can give the mistaken impression that the person is hostile or uninterested.

Estimates vary, but only about three to six in every 100,000 people worldwide, or approximately 20,000 Americans, have PSP, making it much less common than Parkinson’s disease (a movement disorder estimated to have 55,000 Americans diagnosed each year). Symptoms of PSP begin on average after age 60 but may occur earlier. Men are affected more often than women. First described as a distinct disorder in 1964 three scientists published a paper that distinguished the condition from Parkinson’s disease. It was sometimes referred to as Steele-Richardson-Olszewski syndrome, reflecting the combined names of the scientists who defined the disorder.

PSP results from damage to nerve cells in the brain. The disorder’s long name indicates that the disease worsens (progressive) and causes weakness (palsy) by damaging certain parts of the brain above nerve cell clusters called nuclei (supranuclear). These nuclei particularly control eye movements. One of the classic signs of the disease is an inability to aim and move the eyes properly, which individuals may experience as blurring of vision. 

How is PSP different from Parkinson’s disease? Both PSP and Parkinson’s disease cause stiffness, movement difficulties, and clumsiness, but PSP is more rapidly progressive as compared to Parkinson’s disease. People with PSP usually stand exceptionally straight or occasionally even tilt their heads backward (and tend to fall backward), termed “axial rigidity.” Those with Parkinson’s disease usually bend forward. Problems with speech and swallowing are much more common and severe in PSP than in Parkinson’s disease and tend to show up earlier in the course of the disease. Eye movements are abnormal in PSP but close to normal in Parkinson’s disease. Both diseases share other features: onset in late middle age, bradykinesia (slow movement), and rigidity of muscles. Tremor, very common in individuals with Parkinson’s disease, is rare in PSP. Parkinson’s patients benefit markedly from the drug levodopa, while PSP patients respond minimally and only briefly to this drug.

Clinically, PSP results from the accumulation of the protein tau in affected brain cells, while Parkinson’s disease results from the accumulation of a protein called alpha-synuclein.

What causes PSP? The exact cause of PSP is unknown. The hallmark of the disease is the accumulation of abnormal deposits of the protein tau in nerve cells in the brain so that the cells do not work properly and die. The protein tau is associated with microtubules – structures that support a nerve cell’s long processes, or axons, that transmit information to other nerve cells. The accumulation of tau puts PSP in the group of disorders called the tauopathies, which also includes other disorders such as Alzheimer’s disease, corticobasal degeneration, and some forms of frontotemporal degeneration.

PSP is caused by a gradual deterioration of brain cells in a few specific areas of the brain, mainly in the region called the brain stem. One of these areas, the substantia nigra, is also affected in Parkinson’s disease, and damage to this region of the brain accounts in part for the motor symptoms that PSP and Parkinson’s have in common. PSP is usually sporadic, meaning that it occurs infrequently and without known cause; in very few cases the disease results from mutations in the MAPT gene, which then provides faulty instructions for making tau to the nerve cell. Genetic factors have not been implicated in most individuals.

There are several theories about PSP’s cause. A central hypothesis in many neurodegenerative diseases is that once the abnormal aggregates of proteins like tau form in a cell, they can affect a connected cell to also form the protein clumps. In this way the toxic protein aggregates spreads through the nervous system. How this process is triggered remains unknown. Some theories are:  1) That an unconventional infectious agent takes years or decades to start producing visible effects (as is seen in disorders like Creutzfeldt-Jakob Disease); 2) That random genetic mutations happen to occur in particular cells or certain genes in just the right combination to injure these cells; 3) That there is exposure to some unknown chemical in the food, air, or water which slowly damages certain vulnerable areas of the brain. This theory stems from a clue found on the Pacific island of Guam, where a common neurological disease occurring only there and on a few neighboring islands shares some of the characteristics of PSP, Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Its cause is thought to be a dietary factor or toxic substance found only in that area; 4) Another possible cause of PSP is cellular damage caused by free radicals, which are reactive molecules produced continuously by all cells during normal metabolism. Although the body has built-in mechanisms for clearing free radicals from the system, scientists suspect that, under certain circumstances, free radicals can react with and damage other molecules. A great deal of research is directed at understanding the role of free radical damage in human diseases.

What is the prognosis? The disease gets progressively worse, with people becoming severely disabled within three to five years of onset. Affected individuals are predisposed to serious complications such as pneumonia, choking, head injury, and fractures. The most common cause of death is pneumonia. With good attention to medical and nutritional needs, it is possible for individuals with PSP to live a decade or more after the first symptoms of the disease

Is there any treatment? There is currently no curative treatment for PSP. One of the main reasons for lack of curative therapies for PSP and other neurodegenerative diseases is that most of the potentially disease altering drugs do not reach the CNS due to the presence of a physical barrier in the brain known as the blood-brain barrier (BBB). The good news is that ICB International has demonstrated that its SMART Molecules overcome the challenges of the BBB. The Company is now working on developing a BBB permeable SMART Molecule for pathogenic tau protein.

How you can help?The satisfaction of being a part of this historical event can be accomplished by investing in, or finding investors for, ICBII to bring these trials to fruition. Neurodegenerative diseases are on the rise. The good news is that ICBII has developed technology that can potentially halt the disease progression and ameliorate the sufferings of patients afflicted with brain diseases, which was impossible until now. We urge you to join PRO in this humanitarian mission to fight the epidemics of neurodegeneration. Feel free to contact Jo Rosen at Parkinson’s Resource Organization, 760-773-5628 or jorosen@Parkinsonsresource.org.

IMAGINE the world without Parkinson’s, MSA or Alzheimer’s disease. JUST IMAGINE!