PRA Research
How I Began My Research
Being a Libra, it's my fate to endlessly ponder the philosophical nuances of every situation.
If you're one of the rare people who finds out that your dog has prcd-PRA before he has any symptoms, you're in a very small club. In breeds where PRA is a known problem, breeding pairs are typically screened to prevent PRA puppies. Otherwise, you find out your dog has PRA when his vision problems are advanced enough to be detectable--either by a CERF exam, or through his own behavior. But dogs are experts at compensating for vision loss, so it's common for people to only realize that there's a problem after the dog has become completely blind.
In Trevor's case, the test for Goldens became available when he was a young dog. And thus I was handed a crystal ball that told me my dog was destined to go blind.
What this means in practical terms is that there is no body of information on how to deal with a young dog that has prcd-PRA. If you do an internet search for PRA, there is nothing to give you much hope. The disease is universally characterized as an inevitable process for which no treatment exists. The dog's photoreceptor cells are pre-programmed to die. The solution for PRA, according to every website, is to eliminate it through careful breeding. It all made sense, but what about Trevor?
I quickly realized that there was nothing in canine medical literature that could help me. But then I discovered a silver lining: PRA is genetically similar to a human disease called retinitis pigmentosa. Or as one study put it: "Identical mutation in a novel retinal gene causes progressive rod-cone degeneration (prcd) in dogs, and retinitis pigmentosa in man."
Because of this genetic connection, dogs are being used as proxies to study human retinal degeneration, and to test possible therapies. So that is the ultimate irony--whereas "no one cares about treating PRA" since the best way to eliminate it is through selective breeding, finding an effective treatment for retinitis pigmentosa is huge. And dogs are right in the middle of it.
As soon as I understood the connection, I knew that I should be searching on retinitis pigmentosa (RP). I described the beginning of this process in my blog post How I Spent New Years Eve.
My research about RP convinced me that even though PRA and RP are diseases of programmed cell death (also known as apoptosis), there were ways to delay the onset (update 8-19-09: see the conclusion in this article for a discussion of how photoreceptor cell death is different from classic apoptosis). But as always, the devil is in the details. Vitamin A palmitate has been shown to delay RP progression in some percentage of human patients. But this is where it gets tricky, because you can't generalize across species. This especially seems to be true when you're talking about Vitamin A, Vitamin E, and DHA (fish oil), which are powerful agents that often seem to confound researchers by not having the expected results in trials.
Should dog owners mimic what human RP patients do to delay onset? The answer turns out to be no, not necessarily. Contact me personally if you want more background on this.
A Tip on Gathering Medical Information
I joined the retinitis pigmentosa Yahoo! group as a way of learning more about RP. One of the members shared a great technique for following the latest research: set up a Google Alert to send you regular email on news stories containing your keywords.To set up a Google Alert:
- Go to http://www.google.com/alerts.
- Enter the search terms for which you want to receive alerts. I created separate alerts for "progressive retinal atrophy" and "retinitis pigmentosa".
- Specify the type (news, blog, etc.) and frequency of the alert. By default, the settings are comprehensive (i.e., send me results from all available sources) and daily.
- Enter the email address you want the alerts sent to.
- Click Create Alert.
This was an interesting exercise for me to go through, because I immediately realized the following:
- There is a tremendous amount of research going on for RP--everything from diet/supplements to implants to stem cell therapy. Not a week goes by without at least a few exciting new developments.
- The story never changes on the PRA side. All you get is the echo chamber of the internet, repeating the same warmed over cliches on thousands of websites.
Moral of the story: if you think outside the box even a little, there's a whole other reality out there.
RP Treatment: General Topics
2010
2008
This is a good synopsis of treatments for retinal degeneration. It's a presentation that was given by Dr. Gerald J. Chader at the 2008 VisionQuest conference:
Present and Future Treatments for Retinal Degenerative Diseases
This is where I learned about RetinaComplex, which is currently being tested in an RP clinical trial. I've started giving this to Trevor. According to this VisionQuest synopsis from October 2008, "Results from this trial are not yet available but after one year of progress, the unofficial reports are favorable." (page 8)
Here is the original rodent study that led to the human trial.
PRA and RP Research Links
Here are some links for more information:
Researchers
- Leading RP/PRA researcher: Dr. Gustavo Aguirre
- His associate Dr. Barbara Zangerl
- RP: CNTF: William A. Beltran
- RP: Researcher behind original RetinaComplex rodent study: Dr. Theo van Veen
- RP: Researcher behind human RetinaComplex clinical trial (ongoing) -- Francisco Javier Romero
Research Based on Diet/Supplements
- Some RP Patients May Benefit from Beta Carotene (Oct. 18, 2010) -- The AAO-MEACO meeting -- the world's largest, most comprehensive ophthalmic education conference--issued a report on beta carotene's ability to improve vision in people with certain incurable retinal diseases. Another link.
- Seeing is Believing When Nutrition Saves Sight (7-1-10) -- Regularly consuming a combination of the protective nutrients and a low glycemic index diet provided an AMD-protective effect. A food’s glycemic index is an indicator of how fast the carbohydrate it contains will spike blood sugar levels. The nutrients that were found to be most protective in combination were vitamins C and E, zinc, lutein, zeaxanthin, and the omega-3 fatty acids known as “DHA” and “EPA.”
- Lutein, Vitamin A Combo Fights Retinitis Pigmentosa (here's another article) (April 2010). Remember that while Vitamin A may benefit humans, it is NOT recommended for dogs. Excerpt from second article cited:
Those given lutein had a slower loss of vision in the mid-peripheral visual field. Peripheral vision is the area of sight that occurs outside of the very center of vision. In RP, sight is generally lost in this region first as symptoms progress. The researchers estimated that visual sensitivity could be preserved for an additional three to ten years with lutein supplementation.
- Saffron May Stop Vision Loss.
- Followup: positive results from clinical trial using saffron to treat AMD (Jan. 2010). Here is another article about the clinical trial, and an interview.
- New! Followup: One-Year Follow-Up of Saffron Supplementation in Early AMD: Stable Improvements in Retinal Flicker Sensitivity and Visual Acuity. Presented at ARVO 2011(May 2011)
Purpose:
In a previous controlled clinical trial,1 it was shown that short-term saffron supplementation improves retinal flicker sensitivity in early age-related macular degeneration (AMD). The aim of this longitudinal, open-label study was to evaluate whether the observed functional benefits from saffron supplementation may extend over a follow-up of one year.
Methods:
Twenty-nine early AMD patients (age range: 55-85 years) with a baseline visual acuity > 0.5 participated in the study. They underwent clinical examination and a Focal ERG (F-ERG)-derived macular (18°) flicker sensitivity estimate1 every three months over a 12 month period of treatment (saffron 20 mg/day) and follow-up. Visual acuity and F-ERG sensitivity, derived from the estimated response amplitude thresholds, were the main outcome measures.
Results:
After three months of supplementation, mean visual acuity improved by two Snellen lines compared to baseline values (0.75 to 0.9, p < 0.01). Mean FERG sensitivity improved by 0.3 log units compared to baseline values ( p < 0.01). These changes remained stable over the follow-up period.
Conclusions:
These results indicate that in early AMD saffron supplementation induces macular function improvements that remain stable at least for one year after starting the treatment.
- Positive results after first year of RetinaComplex clinical trial for RP (Sept. 2009). Excerpt:
In the placebo group the Multi focal ERG readings taken at the beginning of the study showed a statistically significant difference to those taken at the end of the 12 month period. Patients receiving Retina Complex showed no statistically significant difference between the two sets of data. This confirms that there is a SLOWER progression of disease in the treated subjects compared with those getting only placebo.
- Green Tea Catechins and Their Oxidative Protection in the Rat Eye (Feb. 2010). Hong Kong researchers discover that green tea protects the eye. Here's another link describing the same study: Green Tea May Fight Eye Diseases. Excerpt:
The effects of green tea catechins in reducing harmful oxidative stress in the eye lasted for up to 20 hours, the study says.
- Antioxidants reduce cone cell death in a model of RP
- Taurine keeps immune system strong (mentions RP)
- Fish oil may help protect against retinal degeneration
- Researchers develop new treatment for RP (note that Vitamin A is not recommended for dogs, but I am feeding Trevor canned salmon, mackerel, and sardines. You should NEVER feed dogs raw salmon).
Research NOT Based on Diet/Supplements
- QLT091001 granted orphan drug designation for treatment of RP. QLT Inc. announced that QLT091001, the Company’s oral synthetic retinoid, has been granted orphan drug designation for the treatment of Retinitis Pigmentosa (RP) from the U.S. Food and Drug Administration (FDA) (Dec. 9, 2010)
- Nilvadipine slows progression of central visual field defects in RP (October, 2010) -- Nilvadipine is a calcium channel blocker (CCB) that's used to treat hypertension. In a 30-month clinical trial, Nilvadipine was found to slow the progression of central visual field defects. Additional links:
- Study of drug effects of nilvadipine on retinitis pigmentosa patients. Conclusion: Based upon these results, it is suggested that nilvadipine may beneficially affect retinal degeneration in retinitis pigmentosa patients.
- Potential RP Treatment Based on Ancient Chinese Medicine (October 12, 2010) -- Foundation Fighting Blindness is hoping to sponsor a clinical trial in 2011 to test a vision-preserving agent known as TUDCA (Tauroursodeoxycholic Acid). Based on a traditional Chinese medicine, TUDCA is a synthetically manufactured bile acid that has demonstrated safety and efficacy in animal models of retinal degeneration. Additional links:
- 2005 study that used TUDCA to slow retinal degeneration in mice.
- 2008 study that used TUDCA to slow retinal degeneration in mice.
- 2009 study that used TUDCA to slow retinal degeneration in mice.
- Valproic Acid Shown To Halt Vision Loss In Patients With Retinitis Pigmentosa (July 2010) -- The epilepsy drug valproic acid has shown such promise in initial tests with RP patients that it's now being studied in a 3-year clinical trial. This trial is funded in part by Foundation Fighting Blindness. Additional links:
- Epilepsy drug valproic acid could help in retinitis pigmentosa, study finds
- Valproic acid shows therapeutic benefit in patients with retinitis pigmentosa
- Doctor's Guide: Valproic Acid Shown to Halt Vision Loss in Patients With Retinitis Pigmentosa
- Valproic Acid at Half Normal Dose Shows Benefits for RP Patients
- Microbial Protein Restores Vision (7-23-10) -- Scientists from the Friedrich Miescher Institute for Biomedical Research (FMI) were able to restore vision to a mouse model of retinitis pigmentosa using an archaebacterial protein.
- French Researchers Planning Clinical Study of Vision-Preserving Protein (6-25-10)
- Sight Restored to Mice Afflicted with RP -- Swiss researchers able to reactivate cones (6-24-10)
- Cell Transplants for Macular Degeneration -- Using human stem cells to preserve sight in mice; both AMD and RP (6-24-10)
- Ocuseva (UF-021) eye drops show positive results in Phase II RP clinical trial -- Ocuseva is another name for Rescula (6-3-10)
- New! Followup: Phase 2 Clinical Trial Data of UF-021 in Retinitis Pigmentosa Patients Presented at ARVO 2011 (May 2011) "...the high dose group showed improvement as early as 4 weeks, which continued over time."
- Gene Therapy Restores Vision in Mice -- Scientists used synthetic nanoparticle carrier instead of a modified virus (3-31-10)
- Stem Cells Restore Sight in Mouse Model of Retinal Degeneration (2-24-10)
- Using an implant to seed the eyes with progenitor cells (Jan. 2010)
- Nanoparticles Explored for Preventing Cell Damage
- The 'Holy Grail' of Ophthalmic Devices (artificial retina, or "bionic eye")
- CNTF -- ciliary neurotrophic factor, a neuroprotective agent.
- RP clinical trial for Rescula eye drops (expected to conclude in spring 2010). Rescula has also been suggested as a potential treatment for canine glaucoma.
- Photoreceptor Cell Death Mechanisms in Inherited Retinal Degeneration -- excerpt:
Cell death in inherited retinal photoreceptor degeneration has
often been understood as apoptosis. However,
there are considerable differences between classical apoptosis
and photoreceptor cell death, suggesting the action of
non-apoptotic cell death mechanisms. Based on evidence
collected in recent years, we propose an alternative
molecular pathway as a cause of photoreceptor cell death.
Importantly, this pathway shares none of the major
characteristics of classical apoptosis... This
may have far-reaching implications for the design of
therapies for diseases that, like RP, affect photoreceptors.
While therapeutic approaches aimed at classical apoptosis
have so far been only moderately successful at best, the
recognition that non-apoptotic processes are involved may
open up new avenues and provide a number of new
therapeutic targets.
New! Here is another link that talks about how cell death in RP is not classical apoptosis: Retinitis pigmentosa: a new form of cell death (June 14, 2011).