I don’t know if you all caught what Janet Edmunson (of CurePSP) said at last week’s webinar…
We had heard from Dr. Schellenberg, the lead investigator on the PSP and CBD Genetics Program, back in November that four new genes were found that are implicated in PSP and CBD. These four new genes were discovered by conducting genome wide analyses of 1380 donated brains. (See my earlier November 2009 post on this topic.)
We have at least four local support group members whose loved one’s brains are included in that 1380 pool!
As Dr. Schellenberg indicates in the CurePSP Magazine article copied below, a replication study was to be done with 1000 more PSP cases. This was to be a combination of brain tissue from those with autopsy-confirmed PSP and blood from some still alive who were given PSP diagnoses by a few expert MDs (such as Irene Litvan or Larry Golbe). The replication study was completed a couple of months ago.
We have at least four local support group members whose loved one’s brains were included in that 1000 pool! Three local support group members donated loved one’s brains to local medical institutions not participating in this research.
When Dr. Schellenberg and colleagues did the replication study, they actually came up with six to eight new genes! It depends on the significance threshold. During the webinar, Janet reported that six new genes had been found.
This is wonderful! With this info, hopefully we are on our way to finding some new treatments and some biomarkers (to enable diagnosis while someone is alive) as well as understanding the cause of PSP and CBD and, eventually, prevention of these diseases.
I’ve copied below an article from the most recent CurePSP Magazine about the genetics program. This article mentions the four areas announced back in November 2009.
Thanks to everyone who has donated a loved one’s brain — whether your loved ones were included in this research or not, you may this research possible!
Robin
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Update on the CurePSP Genetics Program
by Richard G. Zyne, President/CEO of CurePSP
Winter 2010 CurePSP Magazine
(which I received in mid-April 2010)
2009 was a most successful year. Not only did CurePSP raise over $4.5 million in gifts for research and education, but the CurePSP Genetics Consortium made some new and preliminary discoveries which could open doors to possible treatment opportunities.
The Charles D. Peebler, Jr. PSP and CBD Genetics Program, funded by CurePSP, has obtained preliminary, unpublished results in its whole-genome analysis for genetic variants contributing to the causation of PSP and CBD. The two-year project has incriminated four areas of the genome not previously suspected of a relationship to PSP or CBD. Each area includes only one or two genes that could explain the findings. The Genetics Consortium is now embarking on a two-month project to replicate those results in a new set of DNA samples. If confirmed, this work will provide new understanding of the cause of PSP and CBD and allow the development of new targets for disease prevention. It could also permit diagnostic testing to identify candidates for future neuroprotective treatment.
The Charles D. Peebler Jr. PSP and CBD Genetics Program comprises 15 scientists (Genetics Consortium), tasked with the job of finding genes that contribute to the cause of PSP and CBD. The group is chaired by Dr. Gerard Schellenberg, a leading neurogeneticist. On September 1, 2009, Dr. Schellenberg convened a meeting of the Consortium in Philadelphia to review its accomplishments to date and to plan its next moves.
The whole-genome analysis, or WGA, started by collecting DNA samples from brain tissue of 1200 people with PSP whose brains had been donated to brain banks and other research collections in North America and Europe and whose autopsies confirmed the diagnosis. 180 DNA samples from brains with CBD were also collected. As these are both rare diseases, accumulating the required number of samples from autopsy-derived brain tissue required a massive effort. Dr. Schellenberg and his European co-chairman, Dr. Gunter Hoglinger of the University of Marburg, in Germany, convinced 20 colleagues in seven countries to donate DNA samples from their labs’ research collections.
For the next step in the project, another Consortium member, Dr. Hakon Hakonarson of the Children’s Hospital of Philadelphia, a specialist in high-tech, high-volume genetic analytical methods, used a recently available “gene chip” to analyze the DNA samples. Each of the chips’ 555,000 compartments carries the chemicals necessary to tell which version of the gene that varies among healthy humans is carried by each sample. Each of those genes is called a “marker” because they are not themselves harmful, but serve only as flags marking locations evenly spaced over all 23 chromosomes. Each marker takes the form of a single “letter” substituted in the genetic code and is called a “single-nucleotide polymorphism” or SNP, pronounced “snip.” The SNP results for the 1380 PSP/CBD patients are compared with results from a population without neurological disorders that was already in Dr. Hakonarson’s database. A SNP whose variants are found to occur in different proportions between persons with PSP/CBD and those without is considered a “hit.”
The result, eagerly awaited for the two years since the project’s conception, was four very clear hits, none of which had been previously suspected of a connection with PSP/CBD. The statistical strength of the four hits was very high, making it unlikely that the findings occurred purely by chance. Three of the four regions included two adjacent genes, only one of which would [likely] be the true culprit on more detailed analysis that the Consortium plans.
The final results of the replication of this work will be conducted in the winter of 2010 with publication to follow in the spring. We all look forward to the completed project and the publication of the findings in a professional journal. But this may only be the beginning of our understanding of the genetic underpinnings of PSP and CBD that may lead us closer to an eventual prevention or cure.
2010 marks the twentieth anniversary of CurePSP and perhaps we will take a major leap forward to achieving our vision of a world free from PSP and CBD.