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Researchers Identify Canine Model of LCA (NPHP5) — Pursue Gene Therapy

Photo of William Beltran, Artur Cideciyan, Gustavo Aguirre and Samuel Jacobson. Photo by John Donges/Penn Vet

William Beltran, Artur Cideciyan, Gustavo Aguirre and Samuel Jacobson. Photo by John Donges/Penn Vet

When scientists embark on developing a treatment for an inherited retinal disease, one of their first tasks is to identify or create a model of the condition. Disease models can be cells in a Petri dish, a genetically engineered mouse or rat, or larger animal such as a pig. Each type of model has its pros and cons, including cost and similarity of disease characteristics to those in humans.

The investigators then use the model to study how vision is lost — that is, they figure out which types of retinal cells degenerate, what is causing the degeneration, and how quickly the cells stop working. After they gain an understanding of the disease, researchers evaluate potential therapeutic approaches using the model as a testing platform.

The goal: Move a therapy into a human study.

University of Pennsylvania researchers funded by the Foundation recently identified a canine model of Leber congenital amaurosis (LCA) caused by mutations in the gene NPHP5. In humans, the condition causes early and severe vision loss from LCA, and in some cases, kidney dysfunction. The investigators found that in canines, the retinal degeneration is remarkably similar to that in humans with NPHP5 mutations, though dogs don’t have the renal dysfunction. The investigative team included: Gus Aguirre, V.M.D., Ph.D., and William Beltran, V.M.D., Ph.D., at the School of Veterinary Medicine (Penn Vet), as well as Samuel Jacobson, M.D., Ph.D., and Artur Cideciyan, Ph.D., at Scheie Eye Institute.

Using the model, Dr. Aguirre and his colleagues are now testing potential gene therapy approaches to eventually slow or halt vision loss, or possibly improve vision, in humans. They’ve already had some success in canines.

“In both humans and dogs with NPHP5 mutations, there is early loss of rods. Cones survive, but have severely impaired function,” says Dr. Aguirre. “In our initial NPHP5 gene therapy studies in canines, we were able to preserve vision and retinal structure at an early stage of disease.”

(Cones are the photoreceptors that provide central vision, and the ability to perceive details and colors. Rods provide peripheral vision, and the ability to see in dim and dark settings.)

Over the last two decades, Penn Vet has made major contributions to the advancement of therapies for inherited retinal diseases having established more than two dozen canine models, including those for: X-linked retinitis pigmentosa, Best disease, cone-rod dystrophy, and achromatopsia. It was Dr. Aguirre and his colleagues who identified a dog breed with RPE65 mutations — including the world-famous canine Lancelot — which helped launch RPE65 gene-therapy clinical trials. Thanks to the success of one of those studies, Spark Therapeutics is now seeking regulatory approval for its RPE65 gene therapy.

Dr. Aguirre notes that LCA caused by NPHP5 mutations is a ciliopathy, a form of disease that is seen in some other inherited retinal degenerations. Specifically, what Penn Vet is learning from the NPHP5-mutant canines may have implications for understanding and treating LCA caused by CEP290 mutations, which is similar in its manifestation to LCA caused by NPHP5 defects.


17 Responses to 'Researchers Identify Canine Model of LCA (NPHP5) — Pursue Gene Therapy'

  1. Lois J Simon says:

    Where can I find a Doctor Who will test me for gene therapy in the Phoenix Arizona area . I am interested in knowing what type of gene mutation I have. Would be much appreciated :-)

    • EyeOnTheCure says:

      Dear Lois, Regarding your interest in obtaining genetic testing to try and identify your disease mutation, please see the following web link to download a PDF document:
      http://www.blindness.org/sites/default/files/genetic_testing_booklet_201311rev.pdf

      Whether your disease gene is identified or not, you should definitely consider enrolling in FFB’s “My Retina Tracker”, a free registry that monitors clinical trials that are recruiting for various retinal diseases. For more information on “My Retina Tracker” please see the following web link:
      https://www.myretinatracker.org/

    • Alieu Kamara says:

      This sounds like a very good news. I hope that the findings become a reality. We’ve been seeing encouraging news like this for over three decades now but with no positive effect on the blind community. RP and other retinal diseases continue to disable people in the United States and around the world. From all indications, “Gene Therapy” may end up taking care of the issue. We pray that it work out soon so that we too can enjoy the gift of sight. May God Bless the researchers!

  2. Muhammad Akbar says:

    I wanted to know when this genes therapy will be available for purblic?

  3. Lois J Simon says:

    Need a gene counselor

  4. Lois J Simon says:

    Yes

  5. Inam Naqvi says:

    My two daughters are having Bardet-Biedl-syndrome. I want to treat their eyes. Please let me know it is is possible by now?

    • EyeOnTheCure says:

      Dear Inam, Bardet-Biedl syndrome is a complex disorder that affects many parts of the body including the retina. Individuals with this syndrome have a retinal degeneration similar to retinitis pigmentosa (RP). Unfortunately, there are no FDA-approved treatments at the present time. However, there are several clinical trials that are currently recruiting people affected by Bardet-Biedl syndrome. For more information on these clinical trials, please see the following web link: https://clinicaltrials.gov/ct2/results?term=bardet+biedl&recr=Open&no_unk=Y

  6. Pasha Hzrat says:

    Dear sir!

    Since 10 years I have eye best’s disease, but no treatment. If you can help me, It would be please to meet you.

    Thank you for your attention.

    Best regards
    Pasha Hazrat

    • EyeOnTheCure says:

      Dear Pasha, You will be happy to know that the Foundation Fighting Blindness is currently funding research efforts at the University of Pennsylvania and University of Wisconsin to develop a gene therapy treatment for Best disease. Already, preliminary data has been published showing that gene therapy can stop disease progression in a dog model. Here is the link: http://www.blindness.org/foundation-news/progress-reported-gene-therapy-development-best-disease. If successful, these research studies will be moved under the jurisdiction of FFB’s Clinical Research Institute which is focused on the development of human clinical trials. There is however, a lot of work to be done before a trial can start. Toxicity and dosing studies in large animals, additional safety studies, generation of a GMP viral vector that can be used in humans and the filing of regulatory paperwork with the FDA are just a few of the things that need to be done before the trial can start. Thank you for your support that is helping to accelerate the development of new safe and effective treatments for inherited retinal disease.

  7. Aisha says:

    Aisha
    Hey I want to know
    address for trement where I can go?
    Please give me .
    I have come rod distrophy ..

    • EyeOnTheCure says:

      Dear Aisha, Approximately 50% of all cone-rod dystrophy is caused by mutations in the ABCA4 gene, the same gene that is involved in Stargardt’s disease. If you have this gene mutation, then you qualify for the ABCA4 gene therapy trial that is currently recruiting patients. Here is the web link for information on the gene therapy trial:
      http://clinicaltrials.gov/ct2/show/NCT01367444?term=stargardt&recr=Open&no_unk=Y&rank=2

      To participate in any gene therapy trial, you must first obtain a genetic diagnosis. For information on genetic testing, please see the following web link to download a PDF document:
      http://www.blindness.org/sites/default/files/genetic_testing_booklet_201311rev.pdf

      Whether your disease gene is identified or not, you should consider participating in FFB’s “My Retina Tracker”, a free registry that monitors clinical trials that are recruiting for various retinal diseases. For more information on “My Retina Tracker” please see the following web link:
      https://www.myretinatracker.org/
      You may also find it helpful to periodically check the website: http://WWW.CLINICALTRIALS.GOV which is maintained by the National Institutes of Health and contains a searchable list of clinical trials for most known diseases. Each clinical trial listing will provide you with information on what the study is about, the requirements for participating and contact information. Thank you for your support that is helping to accelerate the development of new safe and effective treatments for inherited retinal disease.

  8. Ranu Miah says:

    Hi,

    Could I speak to someone more about this. Just recently I have been told I have ROD and I have not come to term of agreeing I have ROD. Can you please help me as its all I have been thinking about. :'(

    Please reply to my email address

  9. Alieu Kamara says:

    Is there an on going clinical trier? If yes how can a patient become a participant?

    • EyeOnTheCure says:

      Dear Alieu,

      There are quite a few clinical trials that are currently recruiting patients. The website: http://WWW.CLINICALTRIALS.GOV is maintained by the National Institutes of Health and contains a searchable list of clinical trials for most known diseases. Each clinical trial listing will provide you with information on what the study is about, the requirements for participating and contact information.

      If you have not done so already, you should consider genetic testing to try and identify the mutant gene responsible for causing the disease. If the gene is identified, medical databases such as PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) can be searched to identify any research that is being conducted. A genetic diagnosis is mandatory for participation in any of the gene therapy trials that are taking place. For information on genetic testing, please see the following web link to download a PDF document:
      http://www.blindness.org/sites/default/files/pages/pdfs/Genetic-Testing-Booklet-V5.2-20151023.pdf
      You should also consider participating in FFB’s “My Retina Tracker”, a free registry that monitors clinical trials that are recruiting for various retinal diseases. For more information on “My Retina Tracker” please see the following web link: https://www.myretinatracker.org/
      Thank you for your support that is helping to accelerate the development of new safe and effective treatments for inherited retinal disease.

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