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Dispatches from ARVO: Day 4 - Valproic Acid revisited

May 5, 2011

by Jennifer Phillips, Ph.D.

Last month, I blogged on some peer reviewed research describing a clinical observation of the effects of Valproic Acid in patients with a particular form of retinitis pigmentosa (not Usher). Today at the ARVO meeting I saw a nice poster presentation that may add a bit more data to that story. The authors, from the same research group at U Mass that produced the original patient study published in the British Journal of Ophthalmology, now report the results of dosing mice with a severe form of RP with Valproic Acid.

This particular mouse model has a mutation that affects the Retinal Pigmented Epithelium (RPE), the cell layer that lies adjacent to the photoreceptor outer segments. The RPE is important for keeping the outer segments-and, by extension, the entire photoreceptor-healthy, and defects in the molecular pathway responsible for the RPE-Photoreceptor relationship often lead to retinal degeneration (the RPE65 gene, which causes Leber's Congenital Amaurosis when mutated, is another example of an RPE gene crucial for retinal cell health).

This mouse strain, with a mutation in a gene called Mertk, has an RPE defect that causes RD very early on in life, with the standard flattening of the ERG and thinning of the neural retina as cells die in large numbers. Unlike the human patients reported in the study by Clemson et al., this form of RP is autosomal recessive in both mice and humans. These researchers gave daily doses of Valproic Acid to Mertk mice over a period of four weeks, beginning when the mice were about 1 month old. ERG amplitudes and retinal thickness were recorded from a group of about 20 control and experimental Mertk mice at the beginning of the period, and again after the four week treatment ceased.

At the end of the trial, the retinal thickness in the Valproic Acid treated mice was significantly greater than that of the control group, indicating that fewer cells had died during the four week treatment period. There also appeared to be some benefit to the ERG response, although not as dramatic as the retinal thickness differences.

So, although there are one or two more controls I would like to see in this particular data set, I can't find too much fault with it, and it does seem to lend more credence to the clinical trial of Valproic Acid treatmemt for Autosomal Dominant RP that is currently recruiting participants, in that it provides another situation in which Valproic Acid appeared to slow the rate of photoreceptor death in a progressive retinal degenerative disease. I'll pass on further developments in this story as they are reported.

Tomorrow is the final day of the ARVO meeing-a shorter day to accommodate everyone's travel plans, but a number of interesting presentations on the program nonetheless. Tune in Friday for one last dispatch from this wonderful meeting.


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