Newsletter - Winter 2012
Dear Friends,
Happy New Year and welcome to the third issue of the Usher III Initiative Newsletter! I am excited to share our news with you and I hope our progress-driven approach encourages you to get involved with our efforts.
We are pleased to announce the first EVER Spin-for-Sight, a fundraiser in New York City being organized by Rebecca Alexander and a small group of dedicated volunteers! All proceeds from this event will benefit our research and we hope you will consider becoming a part of this effort. Please see the Fundraising section below for details on how you can support our first Usher III Initiative Spin-for-Sight.
We have many developments on the research front to report. The Initiative is commencing “Proof of Concept” testing of several small molecule compounds. These tests will be a key factor in determining how to best move forward with a clinical trial for a treatment for Usher III. We hope to have initial results from this testing in time for our next research update meeting in early May. Research also continues at Case Western Reserve University and the University of Florida. Please read more on the progress of our dedicated team below in the Research Highlights section of this newsletter.
We continue to work with the Coalition for Usher Syndrome Research on the development of an Usher Syndrome registry. It is vital for patients to visit the site as soon as it is launched. This is not only important for us to identify patients for a potential clinical trial but it is very important for the steps leading up to any trial including providing demographic and other data needed for regulatory filings. The data collected will also aid us in obtaining available resources for a clinical trial. We will be sure to send out an alert as soon as the registry is launched.
In the meantime until the registry is launched, we cannot stress the importance of all Usher patients getting genotyped in order to find out which type of Usher Syndrome you have. This is absolutely critical and can be done with a simple blood test and without the registry. We encourage you to read the instructions below on how and where you can have your genotyping done. If you have only been clinically diagnosed (based on your symptoms), please read below and learn how you can get a genetic diagnosis. This is critical for you to be eligible for any upcoming treatments that may be available for any of the Usher Syndrome types.
If you haven’t already joined us on Facebook, we encourage you to become a friend on the Usher III Initiative Facebook page today. While these newsletters are great ways to keep you informed, the Initiative’s Facebook page is updated more frequently and allows us to hear from you.
Thank you again for your support!
Warm regards,
Cindy
IF YOU WISH TO JOIN US IN OUR EFFORTS BY MAKING A DONATION, PLEASE VISIT WWW.USHERIII.ORG/DONATE OR MAIL YOUR CHECK PAYABLE TO THE USHER III INITIATIVE TO THE FOLLOWING ADDRESS:
Usher III Initiative
191 N. Wacker Dr., Suite 2090
Chicago, IL 60606
RESEARCH HIGHLIGHTS…
The most highly anticipated work involves testing the small molecule therapy in mice with hearing deficit due to an N48K Clarin1 mutation. Our researchers will test the responses of N48K Knock-in mice for hearing loss using Auditory Brainstem Response (ABR). In earlier testing, it was found that these mice lose hearing rapidly after birth. The Usher III Initiative has developed a small compound molecule designed to stabilize the defective Clarin1 expressed in Usher III patients in the hopes of preserving existing hearing and visual functioning. Now our researchers will treat the mice with the small molecule compounds developed by the Initiative to see if the deterioration is as severe as in untreated mice. If treated mice do not lose hearing as rapidly as the untreated mice, then we would consider this a positive proof of concept in an animal model!
In addition, we are also making progress in understanding how our small molecule candidates interact with Clarin1 protein. Researchers at Cleveland’s Case Western Reserve University are looking to see if the Clarin1 protein binds the potential chaperone small molecules being developed for a potential therapy in a lab in the UK. These studies are important because they tell us if these small molecules are working directly on the Clarin1 protein or on a related pathway. Understanding how these molecules work will help us develop and optimize the compounds as therapeutics.
On the animal model front, transgenic mice developed by our researchers at Case Western were found to express Clarin1 in the photoreceptor inner segments and synaptic regions. This is an important addition to the basic understanding of the Clarin1 gene because it suggests that the Clarin1 gene is expressed in the photoreceptors through adulthood.
Also at Case Western, researchers are using frog (xenopus) tadpoles to look at Clarin1 expression. The xenopus experiment was designed to test the ability of our drugs to penetrate the eye and rescue the abnormal Clarin1 (N48K). While this test does not measure efficacy (the ability to reverse hearing loss), it is significantly faster than our mouse test and, therefore, complementary as the faster results means we can pre-screen compounds in the xenopus model prior to administering them to the mice.
As mentioned above, the Usher III Initiative continues to work with a biopharmaceutical contract research lab to optimize our small molecule compounds for use as safe and effective human drugs. Two series of compounds are being developed, one of which will be used in the animal model hearing testing mentioned above. Further experiments have shown that these two series may work with different mechanisms, offering the potential for more treatment options.
In keeping with the Usher III Initiative’s multi-strategy approach to develop a treatment for Usher III, we continue pursuing gene therapy as a potential treatment. At the University of Florida, our gene therapy research continues as researchers are looking for safe and effective ways to deliver normal Clarin1 genes to the retina. These researchers are also searching for a 'phenotype' or surrogate marker of how effective the gene therapy may ultimately be. In addition to leading to a potential gene therapy treatment for Usher III, this 'phenotype' potentially can be used to gauge the effectiveness of our small molecule therapies as well.
FUNDRAISING IS IN FULL SWING!
We want to thank those of you who have supported our efforts in the past. We hope that this newsletter shows you how far we have come and in such a short time. We are determined to achieve our goal of developing a treatment in the fastest, most efficient way possible.
As we embark on full scale pharmaceutical production in order to achieve our goal, it will require more resources than ever and we hope that you are inspired by how close we are to achieving success. We hope you will join us and be part of a cure to Usher III.
Please consider making donations directly to the Usher III Initiative. You can do so by visiting our website www.usheriii.org or sending checks to the following:
Usher III Initiative
191 N. Wacker Dr., Suite 2090
Chicago, IL 60606
We also invite you to support the inaugural Spin-for-Sight taking place on February 26, 2012 at the Sports Club LA in New York City. If you aren’t able to join us in person, please consider supporting one of the 50 riders supporting our cause.
This event has been spearheaded by fellow Usher III patient and Spin Instructor Rebecca Alexander and a dedicated group of volunteers. It is sure to be lots of fun as Rebecca leads us in two hours of spinning with a break or two in the middle. It will also be a great opportunity to get together with other Usher III patients, share stories, and get fit! All bikes have been filled but if you would like to sponsor a rider, make a donation to support the event, or attend to support our riders, please visit the event website at www.usheriii.org/index.
OTHER WAYS TO GET INVOLVED!
The Usher III Initiative’s top priority is to develop a treatment for patients with Usher III. Our goal is to begin clinical trials in less than 2 years. In order to achieve this goal, patients should begin to plan for these trials now. Because Usher III is an orphan disease which does not affect a large population, it is important that each and every patient join our efforts to prepare for clinical trials. Early gathering of patient information will put us in a strategically better position to get to trials faster.
We urge all Usher III patients to take the following steps to be the most proactive patient you can be:
JOIN THE USHER SYNDROME REGISTRY to be launched online shortly by the Coalition for Usher Syndrome Research. The patient registry is critically important to clinical trials. You can get more information at the Coalition’s website: www.usher-syndrome.org.
GET GENOTYPED. We encourage all Usher Syndrome patients to find out specifically which gene is causing their Usher disease. Many people with Usher have only received clinical diagnosis (this means diagnosis based on your symptoms and not based on a definitive blood test). As a result, some Usher patients have been misdiagnosed as Usher II when a blood test and genotyping may reveal they are actually Usher III. The only way to know for sure is to be screened for one of the many genes that can cause Usher disease. Screening can be done through a medical geneticist locally or through one of the following organizations:
The John and Marcia Carver Nonprofit Genetic Testing Laboratory
University of Iowa
Bill Kimberling, Ph.D.
https://www.carverlab.org/projectusher/instructions
Mount Sinai Center for Jewish Genetic Diseases
Michelle Cahr, MS, CGC
(212) 241-6947
Harvard Medical School and Partners Healthcare
Heidi Rehm, Ph.D., FACMG
(617) 768-8500
http://pcpgm.partners.org/lmm/tests/hearing-loss/usher
If you would like assistance in locating a genetic testing facility, please contact our office via e-mail at info@usheriii.org or by phone at (312) 896-2509.
LOOKING AHEAD…
Usher III Initiative’s Spring Meeting…The Initiative plans to conduct its next scientific working group meeting in May 2012. This meeting provides the research team, the Scientific Advisory Board, and staff with an opportunity to share recent progress, to work collaboratively and strategically to determine the Initiative’s next steps, and to determine our next course of action to achieve our goal of developing a treatment for Usher III. We look forward to reporting news from this meeting in our next newsletter.
Email updates…If you are not currently on our mailing list would like receive updates and exciting newsflashes via e-mail, please visit our website (www.usheriii.org), provide your e-mail address and click on the “Get Notified” button.
Registry… The Coalition for Usher Syndrome Research is working to develop a registry for all patients and medical providers involved with Usher Syndrome. The registry is in the final stages of development. Stay tuned for updates on the launch of the registry.
CONTACT US…
We would love to hear from you! Please feel free to contact us with any questions or comments at the following:
By Telephone… (312) 896-2509
By Email… info@usheriii.org