PSP: SOME ANSWERS( continued)
Insights into the other PSP-related variant in the tau gene were published in 2011 by a group of scientists working in the Charles D. Peebler Jr. Genetics Program, sponsored by CurePSP. The approximate location of this defect in the tau gene is known, but its relationship to the brain cell loss of PSP is not yet understood. This has been the subject of intense research since 2010. CurePSP’ s Peebler Genetics Program has also discovered several other genetic variants that are more common in people with PSP than in those without PSP. One, called EIF2AK3, makes an enzyme that helps control the brain’ s system for disposing of misfolded proteins. This could explain why the clumps of tau protein form. Another gene newly implicated in PSP, called STX6, helps direct the movement of packets of important chemicals within brain cells. Transporting such packets is one of the functions of the microtubules, the internal skeleton or monorail system that the tau protein maintains. A third, MOBP, is the blueprint for the manufacture of a protein in brain cells’ myelin sheath, which serves as a layer of electrical insulation on the wires connecting brain cells together. Still other PSP-associated genes help control the body’ s immune system, although their exact relation to PSP remains unknown.
In 2016, CurePSP, in conjunction with the Tau Consortium, formed the PSP Genetics Consortium, an international team of investigators. Unlike the 2010 study, which was only able to find the approximate location of genes, this effort will work out the genetic code of all genes that make proteins in a group of people with PSP and in a similar group without PSP. This will not only discover additional genes but will also show exactly what those“ typos” in the genetic code are.
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The next step will be to figure out how those errors damage the normal function of brain cells. Those insights, in turn, will provide new ideas for drug targets. In other words, once scientists work out which steps in the brain cells’ normal function become disordered as a result of these PSP-related gene variations, they will know where new drugs could be directed to prevent the process from proceeding further. Coupled with a test to detect PSP in its earliest stages, before it actually causes any disability, such a drug treatment would amount to a PSP prevention. This multistep process is the basis of CurePSP’ s Research Roadmap to a cure.
Could PSP be caused by toxins?
There is evidence that chemicals in the environment or diet may contribute to the cause of PSP. Surveys of PSP patients have shown, on average, lesser educational attainment in people with PSP. This suggests that part of the cause of PSP may be certain occupational factors exposing people to different chemicals than are encountered by people with more sedentary or office-bound occupations. Another possibility is that people with less education tend to live in areas closer to industrial sites, some of which may generate toxins.
One important clue to a possible dietary factor in the cause of PSP comes from the island of Guadeloupe in the Caribbean. People there are far more likely to develop PSP and other atypical parkinsonisms than people elsewhere. A questionnaire survey on Guadeloupe revealed that people there with PSP-like illnesses were more likely than others to have consumed two native fruits called sweetsop and soursop. These fruits have since been shown to harbor toxins that, when given to laboratory rats, cause damage to the brain very similar to human PSP. We don’ t yet know what foods in the Western diet, if any, may contain similar toxins. Research on that question is underway.