Thursday, January 3, 2013

Alan Trounson discusses improved way of studying Fragile X syndrome

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

The full report this month includes two projects that created new cell lines. One could provide a much more efficient way to reprogram one adult cell type into another cell type. This new method looks like it can generate new cells in sufficient numbers to be useful for therapies, something that has been difficult with prior techniques.

I want to focus this blog on the second new cell line paper. It created the first validated laboratory model for Fragile X syndrome, the most common form of intellectual disability. Although scientists have tried to create animal models of Fragile X, the results have always fallen short of mimicking the real condition. They have also tried to create a “disease-in-a-dish” model using cells from Fragile X patients that have been reprogrammed to be stem cells. But that model also failed to mimic the real syndrome.

Part of the problem is the nature of the mutation that causes Fragile X. It results in the loss of a particular protein but only at certain stages of development. Looking at fetal tissue at various stages of development researchers have found this key protein is produced in the embryo and in early stages of nerve development, but the protein disappears as the nerves mature. But in the reprogrammed iPS cells from Fragile X patients, the protein is missing at all stages of development. This was an early indication that iPS cells seem to remember certain aspects of their prior state as adult cells and are indeed different from embryonic stem cells.

The Israeli team that conducted the current project used embryonic stem cells that they created from early stage embryos that had been screened for genetic abnormalities at an in vitro fertilization (IVF) clinic. This so called Pre-implant Genetic Diagnosis (PGD) is increasingly common for couples using IVF services for family planning. It is also an increasingly common way for scientists to create cell lines that can fully mimic genetic conditions. During December, nine of 12 new embryonic stem cell lines registered at the National Institutes of Health were from PGD sorted embryos.

The end result is tools that can yield a much more detailed understanding of these difficult genetic diseases. The Fragile X stem cells created in Israel did produce the key protein during early stages of development and only lost it as the researchers guided the cells to become mature nerves. This model will let us probe the cellular changes that occur as the protein starts to disappear, and also could provide targets for therapy.

Since federal law still prohibits creating any new cell lines with federal funding, this work underscores the importance of funding from private organizations and unrestricted state funding such as CIRM’s.

My full report is available online, along with links to my reports from previous months.

A.T.

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