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Inspired by Progress in Usher Syndrome Research

Dr. Mark PennesiWhen I first heard about Usher syndrome, the leading cause of combined blindness and deafness, I was 19, fresh out of high school and very privileged for the opportunity to work as a summer student at the Retina Foundation of the Southwest with David Birch, Ph.D. I was quite moved by the patients — their eagerness for any kind of treatment and the fear that they might pass their disease on to other family members. That was almost 20 years ago. Back then, we knew very little about the condition, especially its genetic diversity, and there were no foreseeable therapies.

Things have changed. We are closer than ever to having treatment options for patients with this challenging disease. I can now envision a day when we’ll have treatment strategies for all the different forms of Usher syndrome, and I’d like to highlight some of the exciting work that is being supported by the Foundation Fighting Blindness to get us there.

But first, let me give you a quick primer on Usher syndrome. It’s a genetic disease that results when there are mutations (defects) in genes that are important for the function of both photoreceptors in the retina and hair cells in the cochlea, or inner ear. So far, we’ve found 11 genes that, when mutated, can cause different subtypes of Usher syndrome. These mutations usually lead to either a deficiency or defective version of a protein that’s critical for the health and function of the retina and cochlea.

One strategy for treatment is to use gene therapy to introduce new, normal copies of the gene into the remaining cells of the retina. Fortunately, nature has given us the perfect tool for doing this. We can modify viruses, also known as vectors, by taking out the elements that can make you sick and replacing them with the therapeutic gene.

Gene therapy for Usher syndrome is challenging for several reasons — let me highlight two. First, several genes involved are relatively large, and won’t fit in the vectors that have been used in gene therapy trials for other retinal degenerations. Second, by the time Usher syndrome is diagnosed, many patients have already lost a significant number of photoreceptor cells. Gene therapy won’t bring back those cells, but it does have the potential to slow down or halt degeneration — saving a person’s precious, remaining photoreceptors — until other therapies, such as stem cells, become available to replace lost photoreceptors.

At the Casey Eye Institute, we’ve started the first human study of gene therapy for Usher syndrome type 1B, which is caused by mutations in the MYO7A gene. The primary investigator of this trial is my colleague and mentor, Richard Weleber, M.D., who has been studying retinal diseases for almost 40 years. Additionally, Jose Sahel, M.D., and Isabelle Audo, M.D., Ph.D., at Hopital Quinze Vingt in Paris, are participating in this trial. Known as UshStat®, the treatment uses a special vector that can deliver large genes such as MYO7A.

We have treated four participants so far, and hope to enroll the remaining 14 participants in the next year. It’s still too early to know if the gene therapy is working, but the fact that we have moved the treatment into a human study is very exciting.

Other groups are working on new methods to deliver the large genes causing Usher syndrome, such as USH2A, the most common gene linked to Usher syndrome type 2. Muna Naash, Ph.D., at the University of Oklahoma, is using nanoparticles — tiny manmade particles that can readily penetrate cells — to deliver this large gene into photoreceptors of animals.

Gene therapy is just one of the exciting innovations percolating up from the lab into human studies. Jennifer Lentz, Ph.D., is developing a treatment for Usher syndrome type 1C using anti-sense oligonucleotides (ASOs), which are essentially pieces of DNA used to correct mutations. Premature stop codons are common mutations in type 1C and result in a truncated, ineffectual protein. ASO drugs help retinal cells “read through” these mutations so that the entire protein can be made. Premature stop codons often lead to other forms of Usher syndrome and other retinal diseases, so ASOs may benefit many people.

These are just a few of the advancements in Usher syndrome research funded by the Foundation, and we’re making more progress every year. The future has never looked brighter, and it’s quite a thrill for me to be a part of this cutting-edge research.

Pictured, above: Dr. Mark Pennesi.

Mark Pennesi, M.D., Ph.D., is a Foundation-funded clinical researcher at the Casey Eye Institute, Oregon Health & Science University. His research focuses on developing novel treatments for inherited retinal diseases. He is currently exploring the potential of a new class of drugs to up-regulate protective growth factors in the retina.


24 Responses to 'Inspired by Progress in Usher Syndrome Research'

  1. BRENNEIS says:

    Thanks for every other informative site. The area altogether different could I get in which sort of info designed in such an ideal technique? I own a business that I am only at this moment managing with, i have been for the seek out similarly info.

  2. Patricia Newman says:

    I am 74 years old with Usher’s.

    I have Usher’s Syndrome and have recently been diagnosed with ARMD and Retinal Vitreomacular Traction. I have a cochlear implant in one ear since 2004. I also have a genetic cataract in left eye since birth. Goodness, I am 74 years old and I do hope a breakthrough does come while I’m still here :) If I can be of any help in the trials I would love to be a part of it.

    i also have ARMD

  3. Denise R Cherico says:

    56 years old here I ave diagnosis for RP
    going deaf past 4 years so no doubt have USHERS # too
    having a diffult time
    life is getting more difficult no kids no husband poor sister is doing more for me now. no pain so grateful for that
    peace

  4. Rose says:

    I was diagnosed with Ushers type 2 back in 1982, just a few days ago I got my DNA sample sent to Carver Lab Ohio. I hope to be part of future trials. We are in exciting times! Right now it’s a waiting game

  5. Sue Patterson says:

    My sister has this and she is 56 and I pray they come up with a cure and treatment soon.

  6. Craig says:

    My wife has Ushers Syndrome and it depresses her that her condition continues to deteriorate. This article is an encouraging developments but she has given up on a cure because we’ve been hearing of hopeful encouraging developments for years. I wonder what kind of timeline before a cure is actually made. Having said that, I love the dedication and efforts of these researchers. God bless them.

  7. Edee says:

    I do not have Usher Syndrome & know very little about it, other than that it causes both deafness & blindness. I have an incurable inherited retinal degenerative disease & usually just focus on vision loss. I came across this article by accident, but I found it very informative & interesting. I had no idea that there are 11 different genes whose mutations can cause Usher Syndrome, & I didn’t know there were so many different subtypes of the disease.

    Thank you for helping to keep people informed of the research progress, & thank you for devoting your career to finding treatments & cures for Usher Syndrome.

  8. walker jones says:

    I have Usher syndrome I was born hearing impaired I have wore hearing aids since I was 3. I am 19 and I have a son who will be 2. I get social security but that is not enough for me to live by myself and take care of my son. I was wondering if there are any institutions that can help me. I just read where they are doing research. I would like to know if I am a candidate for this. I really need help. Please contact me if you know of anything that will help me. Thanks

    • EyeOnTheCure says:

      You might want to contact the National Federation of the Blind (https://nfb.org) that has resources to help people with vision disabilities get training and find jobs. As you may know, there are three types of Usher syndrome and 12 different genes. Therefore, You may also want to try and identify your disease gene as there are already several clinical trials for Usher syndrome that require a molecular (genetic) diagnosis to participate. 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

      You should also consider participating in FFB’s “My Retina Tracker”, a free registry that can help you find out about clinical trials that are recruiting for your specific disease. For more information on “My Retina Tracker” please see the following web link:
      https://www.myretinatracker.org/

      If you have any other questions or concerns, please feel free to contact me.

      Timothy J. Schoen, Ph.D.
      Director, Constituent Communications
      The Foundation Fighting Blindness

  9. Elena says:

    50 years old, Usher Syndrome 2A, was diagnosed in Alaska in 1993 at age 29. At that time I was prescribed Vitamin A 15,000 IU Palmitate. In 2014 I got my Cytogenetics results through the Division of Human Genetics at Cleveland Clinic, Ohio. They are Allele 1: c.4174G>(p.G1392*) and Allele 2: c.14792-2A>G. I contacted Dr. Naash in 2012. FFB (Foundation Fighting Blindness) Newsletter keeps us update on clinical trial studies as well. As of today, I have a little “hole” of central vision left. Very scary. Your article gives us a very promising light of hope. Thank you!

  10. Mervat says:

    Hi , thank you for every thing ,,
    My name is merva 29 years old and lives in England, and I am suffering from Usher syndrome since childhood you suffer from hearing impairment and a weak gradual eyesight gradually I feel that my condition gets worse every day afraid of the future, but I pray to God to draw closer to the treatment and I have great hope and healing. I have complete and ready to participate in any research experience to get to this treatment and my emil in case you want to communicate with me
    mervat_salameh@yahoo.com

  11. Pat Hanten says:

    My almost 2 yr old granddaughter had genetic testing. My daughter was told that my granddaughter has about a 70% chance of having Ushers 3. We are living under such a cloud. Right now her vision and hearing are normal but she does have Congenital Nystagmus.

  12. Pat Hanten says:

    I didn’t finish my comment. We are desperate to know how viable a treatment is for Ushers for a baby diagnosed with it today. Will it likely happen in her life time????f

  13. Linda says:

    My daughter is 31 years old with Ushers Syndrome. She is married with two beautiful children a 6 year son and 3 year old daughter. Within the past two years her vision has diminished greatly. She is desperate and becoming depressed. She would be willing to participate in any trial. Is it possible for her to be a candidate?

  14. Dawn M Horn says:

    I am full deaf and legal blind. I am usher syndrome type 2 and r.p. too I wait for find cure.

  15. Christine M says:

    My husband and I just found out that our beautiful 5 year old daughter has Usher Syndrome Type 2. She was born with mild to moderate hearing loss and has hearing aides since October. My husband and I are both devastated by the news and feel lost on what to do next. We are encouraged by this article that there amazing doctors who are working to find a cure and hope that our dear beautiful girl will benefit from their research.

  16. Robert Skaggs says:

    Hi, I’m 39 years of age, was diagnosed at age 25 years old and never knew I had Usher type 2 till I went to Rochester, NY, where a teacher saw the symptoms so had and went to Strong Memorial Eye Institute, where I had cataract surgery done there back in 2000. Never seen intricate designs on a bark of a tree before till I had the surgery. I wear bifocal glasses now. I have a family and two boys of which were diagnosed with no diseases of which I have and no hearing issues at all either. I wonder if this has to do with AGENT ORANGE. My brother 5 years older than me all of a sudden is developing myochrondial disease, I have Usher type 2, my brother has mental illness. Doctors tell me it’s a recessive gene. Couldn’t the AGENT ORANGE mutated my Father’s gene? Anyways if there is ever a cure by injection in the eye like I heard of that dog who were once blind but now can see, as seen chasing a ball on national TV, I want that! I do not want dots to tell me what’s in front of me, no black and white, or shapes I have to figure out what’s in front of me. I’m a very productive man! Hope there is something out there for me with retinitis pigmentosa/ Usher Syndrome 2

    • EyeOnTheCure says:

      To my knowledge, there is no evidence suggesting that exposure to Agent Orange could result in germ line mutations that lead to Usher Syndrome. Presently, there are no clinical trials for Usher type 2 or 3. However, FFB is funding a study at the University of Oklahoma to develop a non-viral gene therapy approach for treating Usher type 2A. For more information, please see the following link: http://www.blindness.org/blog/index.php/a-bigger-boat-for-nanoparicles/. You should consider genetic testing to try and identify the mutation in the Usher 2 gene that is responsible for causing the disease. If the gene is identified, medical databases such as PubMed can be searched to identify any research that is being conducted. With a molecular diagnosis, one may also qualify for 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

      Whether the disease gene is identified or not, one should still 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/

  17. Nanette says:

    I was reading the above story. My niece has Ushers disease and is 30 years of age.I don’t know what type but she has been wearing hearing aids and can barely see a foot in front of her self. Her father was mentally ill. I wonder if there is a connection.

  18. Terry Wilson says:

    My name is Terry and I have been diagnosed with Usher syndrome since I was 5 years old I’m a 30 and I have dealing with half my vision and have lost 42% of hearing I have Usher syndrome type 2 please consider me for your study thank you for your research and everything you do
    God bless

    • Dr. Tim Schoen says:

      Dear Terry, If you have not done so already, you should consider getting a genetic test to verify mutations in the Ush2A gene. For information on genetic testing, please see the following link: http://www.blindness.org/sites/default/files/genetic_testing_booklet_201311rev.pdf
      Additionally, you should consider enrolling in “My Retina Tracker”, a free registry that can help you find out about clinical trials that are recruiting. For more information on “My Retina Tracker” please see the following web link: https://www.myretinatracker.org/
      The Usher 2A gene is very large and scientists are currently trying to find a way to splice the Ush2A gene into a virus for gene therapy delivery. Hopefully, they will be successful and clinical trials will start within the next 3 – 5 years.

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