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Wednesday, June 30, 2010

My First Deafblind Party

by Mark Dunning

We're heading in to summer so the posts will be more spaced out. Here’s a quick one for you. Julia and I recently attended our first deafblind party and I thought I’d tell you about it.

Let me stop there and put this in a larger context. First, I’m a little embarrassed that this is a big deal. I don’t want it to sound like I went to the zoo. These were real people, after all, and I have a great respect for them. But I don’t know them all that well and the usual apprehension that goes with a social event with unfamiliar people was compounded by the fact this was also an unfamiliar setting for me.

Second, prior to Bella’s diagnosis almost four years ago and I had no experience with blindness. Heck, prior to her birth I had not experience with deafness, either. Like most parents of children with Usher syndrome, I am terrified of what the future might hold for my daughter. And, like a lot of families, I didn’t want to know if it’s going to be bad.

So I avoided adults with Usher syndrome for a long time. I was afraid they would lead a difficult life, a lonely life, a life without joy. I had done the same thing with deaf adults when Bella was first born. I just didn’t want to know.

I find this with lots of families of children with Usher. They avoid conferences and deafblind functions. They don’t want to connect with adults with Usher. Part of it is that many adults with Usher were born long before cochlear implants and digital hearing aids, so most of them sign. This furthers the divide between newly diagnosed Usher families, the majority of whom do not sign. Add in that the sign language is often tactile sign and newly diagnosed families find the communication all the more difficult. This feeds their anxiety. They picture their son or daughter using tactile sign, speaking to them through an interpreter, and it scares them to imagine that distance between them and their own child. I know it scares me.

But those that read this blog know that I am a vocal advocate for building an Usher syndrome community for both practical reasons and personal reasons. Practically speaking, to find a cure is going to require the efforts of all Usher families. We need your natural histories, your genetic information, your experiences, and yes, your money (or at least the money you might help raise). Eventually we will also need Usher families to participate in clinical trials and the best candidates for those initial trials are Usher adults.

On a more personal note, I want a cure for my daughter. I don’t want her to go blind. The only way that is going to happen is if Usher adults and other Usher families are engaged in the process. And, as I regularly advocate, the only way to keep families engaged, whether they be newly diagnosed or older adults, is to connect with them and build an Usher community.

So that’s what I do these days. I connect with Usher families and with Usher researchers. I have made a ton of great friends through it and many of them are Usher adults. Still, most of my communication is through e-mail and I do not often meet deafblind adults outside of conferences where accommodations are made and professionals are around. So my experiences in the ‘real’ world are few.

My first real experience with blindness came at a dinner several years ago with a well known blind author. We were both traveling in Seattle and staying at the same hotel. I was terribly nervous meeting him, more because he was blind than because he was relatively famous. But he was gregarious and funny and dinner turned out to be memorably fun. Especially when we left the restaurant a number of drinks later and I realized I didn’t know how to get us back to the hotel. This led to several wandering blocks of ‘the blind leading the blind’ jokes from my companion and at least one trip into a hedge when I forgot that I was leading him. Thankfully he had a good sense of humor.

But this was my first deafblind party. This was the first time that I would be immersed in the daily life of adults with Usher syndrome. I was very nervous. It helped that my wife Julia was with me. At least one of us could fake an injury if we couldn’t handle it.

There were 15-20 people at this party. About a half dozen of them had Usher syndrome. All were adults. All had pretty severe vision problems. But their communication varied. Some only used sign language. Some used a combination of spoken English and sign language, depending on the audience. And some used spoken English exclusively. Most of the sighted party members knew sign language, too, and there were several interpreters about, so communication was surprisingly easy.

I sign a little, but mostly I needed assistance communicating. I did not follow etiquette very often. You have to wait to reply when someone is using an interpreter and, well, I have a big mouth and I’m from Boston so I tend to talk over people and talk very fast. By the end of the night I had it down, though.

And the conversation was wonderful! These were fascinating people. There were college professors and state representatives. People had travelled the world, written books, and been on the radio. The party was to celebrate the success of a recent deafblind day at the state house and there was a declaration signed by the governor that was passed around. Forget faking injuries. Julia and I didn’t want to leave. I went in expecting a bunch of silent, moping people sitting in the dark bemoaning their fate. I found one of the most upbeat, positive, energetic, and capable group of people that I have ever had the pleasure of meeting.

Now, this is not to say that the night went entirely smoothly. The guide dogs were let off their leads and they partied like sailors, tearing around the house and knocking over anything in their path. Since their owners (is that the right word?) couldn’t see them, the dogs were usually one step ahead of retribution. A lamp would break and by the time everyone turned to the sound, the dog was long gone and the owner was yelling at the vacant rug. Julia and I have two dogs, one of whom is a conniving son of a gun, so we could relate.

Even more humorous was the making of dinner. Our hostess, who has Usher and can not see or hear very well, insisted on command of the kitchen. She was making pasta in a giant cauldron and was completely oblivious to the boiling water spilling everywhere. It was an open floor plan and those of us without Usher could all see what was happening so, one by one, we stepped in and offered to help. And one by one, we were shooed away. At one point I was standing with her husband as she knocked over a bottle of wine and grabbed a knife by the blade as the pot boiled over and I said, “Uh, should we offer to help?” He just waved a hand as only a husband can and said “Nah. She’s fine. She wouldn’t accept help anyway.” Boy, did he know his wife.

The good news is that our hostess survived the making of dinner and the house did not burn down. I’m pretty sure her husband would have stepped in if fire broke out, though knowing our hostess, I’m also pretty sure he would have been swiftly shooed away. And dinner was excellent. I’m not just saying that. It was really excellent. Better than I could have made (though I struggle with grilled cheese, so that’s not saying much).

So we had a great time at our first deafblind dinner. But that’s not the point. It could just as easily have been packed with dullards and been the most boring three hours of my life (next to that time I watched Waterworld). The point is that we have to find ways to bridge the divide between Usher adults and families with Usher children. We need each other. We can learn from each other. And there is no one that understands us better. This is not to suggest that every Usher family will like every other Usher family. We’re a cross section of the population at large. You’ll click with some and not with others. But you have to try for your own good or for the good of your children. And you never know, you might just wind up having a great time. Who would have thought that would come from an Usher diagnosis?

Monday, June 14, 2010

Solutions, Part I

by Mark Dunning

Editor’s note: This is a planned public debate between Mark Dunning and Jennifer Phillips, the two primary contributors to this blog. The ideas expressed in the posts during this debate will be purposely provocative and unfinished to invite a response from the other party. We hope you find the discussion valuable.

It seems like this is a good time to start discussing solutions rather than problems. First, a truth, since I know you can handle it: I don’t really have much resentment toward researchers. The truth is a lot of them have become good friends of mine. I am amazed by the hours they work and the amount of dedication they have. In fact, it was the willingness and downright eagerness of three researchers to include me in the process that gave me the confidence to stick my nose in all of this in the first place.

I now know many (if not all) of the top Usher syndrome researchers in the world. They treat me like a peer even though I’m not. They never withhold information and actually appear to take great joy in educating a neophyte like me (most of them are professors, after all).

But my frustrations with the communication between families, researchers, and physicians is very real. I have burrowed in to the research community, but how I got here was all trial and error. I feel very fortunate to have gotten access to the information I have. I didn’t leave a trail of breadcrumbs for other families, however, and quite frankly it took a LOT of time, effort, and luck. Most families don’t have the resources available to them that I did.

One of the comments on Jennifer’s last post struck a chord with me. It was anonymous, but it was clearly posted by a family member well versed in research (the writer mentioned glial cells, for goodness sake). As I read it, I could hear the pleading of the writer for information. The writer mentions hearing about a potential treatment in 2008 but not hearing anything about it since.

The post rings with questions: Has nothing happened since then? Did it get dropped? Did they find out it’s not going to help? Did they just hit a roadblock? Do they need money to pursue it further? Who’s working on it? If I give money, will it get to them? How can I help?

No one answers these questions for families and that makes them, as this particular commenter put it, ‘frantic’. Jennifer’s 911 call would be a good metaphor except that for families with Usher syndrome, there is no number to call, no dispatcher to talk them down, and no siren in the distance to let them know help is coming.

So that’s where we stand in the debate. How do we get researchers the tools and information they need while keeping families involved in the process? How do we overcome the fear of false hope while ensuring that frantic families are informed?

Once More, From The Top, With Feeling

It all starts with the communication process of the initial diagnosis. Hope in the diagnosis is not a luxury. It’s a necessity. Every time a family with Usher syndrome is so devastated by the diagnosis that they never get genetically tested, never go back to the doctor, and/or never share their natural history information, it limits our overall knowledge about the disease and lengthens the timeline to a cure. It also limits the available pool of candidates for clinical trials which may delay them or even keep them from happening.

We need to keep families engaged, and that makes hope as important as fact to finding a cure. Families that believe we can help them, whether it be today or in the future, will stay in touch with us and remain involved in the process. So, going back to my opening salvo, facts need to do what I want them to and that’s support the case for a hopeful future. Remember, as I wrote previously, we can handle the truth. (And, yes, I did actually write that, Jennifer. I must say that using my actual quote against me in your last post was dirty pool.)

So here are some truths that families should know as soon as Usher syndrome is suspected:

1. The truth is that while there are no proven treatments for Usher syndrome, vitamin A is often prescribed. It might help with Usher syndrome, it might not, but it is generally considered safe in proper doses, especially when combined with regular tests of liver function . Most importantly, it offers hope to families that take it because they are doing something to help themselves or their loved one.

The same can be said for other dietary changes like DHA (Please note that I say dietary changes, not supplements. That’s different.). The truth is that most kids (and many adults) hate to eat fish but it’s good for them and not just for their eyes. Whether or not you have Usher syndrome you should probably work fish that’s high in DHA in to your diet (unless, of course, you’re allergic in some way). Lutein is the same. It’s found in spinach and broccoli and other stuff kids hate, but it’s good for them and they should eat it whether they have Usher syndrome or not.

It is also the truth that sunglasses make you look cool, so if there is a chance they might slow the vision loss, you should probably wear them. They offer hope and the chance to look like a rock star.

2. The truth is that there are a number of treatments in development, many of which hold a lot of promise. Gene therapies have worked in clinical trials for other related disorders and there are a number of groups that intend clinical trials on Usher syndrome treatments.

3. The truth is that before any treatment can be used in humans, it needs to be tested in animals. The good news is that there are animal models for Usher syndrome. True, they have not consistently demonstrated the vision phenotype, but there are a lot of good people working on it that believe we will have one that does very soon (I’ll write more about this in a later post). It will be about thirteen nanoseconds before all those treatments under development are tried on an animal model that has the vision phenotype once it’s developed (OK, that’s probably not the truth, but it will happen quickly)

4. The truth is that these treatments under development are, depending on the treatment, 5-10 years away from helping you or your loved one, but we don’t know for sure when, or if, they will ever arrive. Sorry. It’s a hard truth, but you can handle it. However, keep in mind that…

5. The truth is that we don’t know enough about the vision loss associated with Usher syndrome to know for certain the rate of deterioration that any individual faces. In short, we don’t know when, or even if, you or your loved one will lose their vision. What we do know is that the vision loss is progressive and that, except in rare cases, most people with Usher, regardless of type, retain some useable vision until later in life.

6. The truth is that, when you consider the number of treatments under development, the time frame for delivering those treatments, and the rate of vision loss (which may or may not be slowed by sunglasses, DHA, vitamin A therapy, lutein, anti-oxidants, or other potential dietary changes), a child born today with Usher syndrome has a chance of NEVER LOSING HIS OR HER VISION.

See? Families can handle those truths, right? Now, a lot of what I proclaim above as truth might not be so quickly supported by others (I won’t get in to the vitamin A debate again, for instance). However, even if a physician disagrees with any of the above and does not want to share it with families, I believe he or she, at a minimum, has a duty to tell families the following facts (note I said facts, not truths):

1. The majority of people with Usher syndrome that want to go to college go to college.

2. The majority of people with Usher syndrome who want to get married, get married.

3. The majority of people with Usher syndrome who want to have children, have children.

4. The majority of people with Usher syndrome who want to pursue a challenging career, pursue a challenging career.

In short, the majority of people with Usher syndrome live happy, fulfilling lives. That, above all else, is the fact that families seek and all too often it is never mentioned to them by anyone.

Thursday, June 10, 2010

The Debate Goes Thermonuclear

by Jennifer Phillips, Ph.D.

Editor’s note: This is a planned public debate between Mark Dunning and Jennifer Phillips, the two primary contributors to this blog. The ideas expressed in the posts during this debate will be purposely provocative and unfinished to invite a response from the other party. We hope you find the discussion valuable.

So the good news here is that Mark and I agree on many of these debate points. This is great because it gives us a stepping off place from which to brainstorm about our common goal of improving the flow of information between researchers, clinicians, and families. The bad news (well, bad for Mark, anyway) is that before I can deal with that good news I have to don my sturdiest firefighting attire and tackle the noxious and incendiary content emanating from portions of Mark’s last post.

Figure 1: “Dear Dr. Phillips” preparing to rush into the blazing thicket of WRONG!

Stop, Drop & Flip-flop

In the intro to his last debate post, Mark concedes the point that research scientists do, in fact, talk to each other—or does he? After opening with comments that seem contra his original position, he claims to never have held that position in the first place, stating “I merely said that researchers give the impression that they don’t talk to each other”. Well thanks to the marvels of the internet , we have a handy record of what Mark actually did say, back on April 29th. To wit:

“Researchers are loathe to discuss any research that is currently underway because until the results are not only in but have been peer reviewed, they can not be trusted to be fact…Many researchers take this secrecy to the point that they won’t even discuss what they or others are working on.”

Hmmmmm…Well, perhaps he meant to say that “Researchers merely give the impression that they are paranoid control freaks”. Either way, I think we can consider this “impression” falsified, at least in the generalized manner in which it was originally applied, and move forward.

Shouting “Fire!” in a crowded Symposium

In mulling over how to reply to Mark’s June 3rd post, relating his experiences at the Usher Syndrome Symposium, I reconceived our dialogue in in the form of a 911 transcript. The ‘Caller’ script recapitulates portions of Mark’s last contribution to this debate:

Dispatcher: “911, what is your emergency?”

Caller: Help, Operator! “Few families actually saw what was going on or heard any of the presentations” and “The information was also brutally technical and scientific”!!

Dispatcher: Stay calm, sir; given that this was a professional conference targeting clinicians and scientists rather than families, unrelenting technobabble was completely appropriate—necessary, even!—to convey the important details of these cutting edge scientific studies.

Caller: But…but, “The Researchers Are Too Distant From Their Real Purpose!” “I got the sense that a child with Usher was a rarity in their lives when, in truth, they probably should all have a picture of a patient with Usher taped above their door.”

Dispatcher: Sir, please, you seem to be having difficulty separating your personal investment in identifying a cure for Usher syndrome from other more professional motivations for pursuing research in this area. Let’s say you can persuade every researcher currently working on Usher studies to prominently display a picture of an Usher patient. It probably wouldn’t be difficult, as you concede that at least some of the researchers you have interacted have acknowledged the important perspective that patient interactions can offer. Then what? Will the presence of these pictures inspire formerly indolent or indifferent researchers to greater works? The insinuation here is that researchers who don’t have regular, personal contact with Usher patients (or, indeed, this could easily expand to any basic research field with potential clinical impact) aren’t sufficiently motivated to fully apply themselves to their professional endeavors. That’s deeply insulting, and, more importantly, spectacularly wrong. To suggest that we’re just not that into it because we don’t have a personal stake in the outcome is an absurd mischaracterization. It is undeniable that a personal connection to Usher syndrome would be motivating to someone contemplating a career in research and/or medicine. However, it is far from the only motivator, and absent any further evidence, I reject the assertion that this personal stake is a prerequisite for professional commitment.

Caller: Well, yeah, but “In the end, the families are all that matter. Even if you were an empty hearted researcher you would have to recognize that without Usher families, you don’t have a job. No one cares about developing an Usher syndrome animal model if no one has Usher syndrome!”

Dispatcher: Sir, human biology is incredibly complex. And within that broad category, Usher syndrome is just one of many phenomenally complex diseases. As thinking feeling human beings, we hope fervently that our research will to contribute to future treatment options. As professional scientists we are required to focus on the really nitty-gritty complexities of the system—and we like it! Most of us didn’t become Usher researchers because we know someone with Usher and wanted to help them. Most of us got here because of a deep and abiding interest in understanding complex molecular/cellular sensory processes. Usher syndrome research provides us with abundant complexities to which we can apply our collective decades of scientific training and problem-solving skill sets. Furthermore, just like content of the meeting that you found so dense and unpalatable, it is necessary for scientists to consider the fine and intricate details of Usher pathology at the cellular and molecular level. That we may not also consider the existence of patients and families awaiting a cure from the fruits of our labors during every phase of the experimental process is NOT a liability. In fact, I should think you’d prefer us to have our full attention on the nitty-gritty. Let us attend to the task of figuring out how things work with obsessive, laser-like intensity. Once we gather those data, we can proceed to the logistic steps of incorporating them into a treatment option, but we cannot skip or hasten the first step without running the risk of laying a shaky foundation for all that is to come.

Banking the embers

Ok, I think the smoke and fumes have dissipated enough—for now—to get to the more substantive issues. For me, those issues involve identifying ways in which we ALL--Patient families, Clinicians, and Researchers--can improve and expand our communication with each other

The concerns Mark and I have voiced about withholding or selectively disseminating information, about media coverage, and overall about patient access to the research findings that could benefit them are complex, but addressable. The tricky part of this, of course, will be agreeing on the best ways to address these problems. Discussion of the pros and cons of different solutions will, I think, be the principal topic of the remainder of our open debate. I have some specific ideas about how to proceed; I know Mark does too, and it’s probably not too much of a stretch to predict that our respective opinions on what constitutes the best choices will not perfectly align. But it’s a conversation worth having, and I’m looking forward to the process. As we flesh out some of these ideas for public consumption, I hope that our readers will get involved in the discussion as well, so don’t be shy about commenting!

Wednesday, June 9, 2010

Usher syndrome Family Conference, July 10, 2010

by Mark Dunning (biographical sketches by Karmen Trzupek)

Jennifer and I have been debating the difficulty in establishing and maintaining relationships and open communication between researchers, professionals, and families. The family conference in Seattle on July 10th is a great opportunity for families not only to connect with other families, but also to meet and talk with some of the leading researchers and Usher syndrome professionals. I strongly encourage you to attend if you can. Both Jennifer and I plan to be there and would love for the chance to meet our readers.

Here’s the link to register and some information on the presenters:

Dr. William Kimberling, PhD
University of Iowa and Boystown National Research Hospital
Dr. Kimberling is internationally known as an expert in Usher syndrome, with over 30 years of experience in the clinic and in the laboratory. Over that time, he has received many federal and private grants to study Usher syndrome and related disorders. Through these studies he and his collaborators have been responsible for the identification of four of the nine Usher genes. He currently holds a dual-professorship at Boystown National Research Hospital and the University of Iowa, where he is working with Dr. Edwin Stone to develop an inexpensive but accurate means of screening young children for Usher syndrome.

Linda Ramsdell, MS, CGC
Seattle Children's Hospital

Linda Ramsdell is a certified Genetic Counselor working in Medical Genetics at Seattle Children’s Hospital. Since becoming certified in 1993, Linda has been involved with a variety of specialty genetics clinics at the University of Washington. She now works closely with Dr. Kathy Sie, director of the Childhood Communication Center, and co-director of the Pediatric Cochlear Implant Program at Seattle Children’s, to provide genetic counseling, testing, and support to families with inherited forms of hearing loss. Linda also serves on the Genetic Services committee of the National Society of Genetic Counselors (NSGC.)

Peter Francis, MD, PhD
Oregon Health & Science University

Dr. Francis specializes in research and medical care of the retina and has a particular interest in ophthalmic genetics, practicing at Oregon Health & Science University. He is intimately involved in the design and execution of current and upcoming clinical treatment trials for inherited retinal and macular dystrophies, working closely with the Foundation Fighting Blindness. Dr. Francis directs a stem cell research lab at the new Biomedical Research campus at OHSU. Prior to joining OHSU, he practiced at St. Thomas' Hospital in London, and was director of undergraduate teaching at the medical school for Guy's, King's College, and St. Thomas' hospitals in London. He is also is the editor of the ophthalmology review journal “Ophthalmology International.”

Jim Phillips, PhD
University of Washington

Dr. Phillips is the director of the Dizziness and Balance Center with the department of Otolaryngology at the University of Washington Medical Center, and the director of the Clinical Oculomotor Laboratory within the Division of Ophthalmology at Seattle Children’s Hospital. His work bridges the gap between the research laboratory and the clinic, translating scientific theory into practical tools for assessment of patients. Dr. Phillips studies the genetics of vestibular function in mice, basic physiological mechanisms in non-human primates, the development of behavior in infants and children, and the behavioral consequences of disease and developmental disorders in patients.

Dorothy Walt
Helen Keller National Center

Dorothy Walt is a regional representative for the Helen Keller National Center, northwest region. She earned her M.A. in Rehabilitation Counseling from Gallaudet University and has worked in the field of deaf-blindness for over 15 years. After starting and managing a statewide deaf-blind program in Anchorage, Alaska, Dorothy accepted a position as a HKNC regional representative and became involved with advocating for deaf-blind people nationally and worldwide. She now lives in Seattle.

Nancy Hatfield, MS, PhD
Washington Sensory Disabilities Services

Nancy Hatfield has worked with Washington Sensory Disabilities Services since 1992 to enhance statewide capacity to meet the needs of children and young adults with sensory disabilities. She co-directs the deaf-blind project and coordinates early childhood activities, as well as functioning as administrative director of WSDS staff and grants based at Puget Sound ESD. Nancy holds a B.A. in Speech Pathology/ Audiology and a M.S. and Ph.D. in Education and Human Development. Nancy's prior work experience includes early intervention services for families with infants and toddlers who are deaf, hard of hearing, and deaf-blind. She wrote grants for and directed Project SIT-UPS (Sensory Impairment Training to Upgrade Professionals' Skills) and the Shared Reading Video Outreach Project.

Amelia Westerfield

Amelia Westerfield is a recent master’s degree graduate of the University of Washington’s School of Social Work. Together with her husband, she lives and works independently as a social worker, and is an ardent supporter of local outreach programs and fundraisers serving the deafblind community. She recently wrote an article for the Oregon DeafBlind Project entitled, “Thoughts on Transitioning: One DeafBlind Woman’s Approach to Life.”

Katie Humes

Katie Humes has an extensive background with young children with hearing loss, including children with multiple disabilities. She has a Masters in Education, with a specialty in infants & toddlers with hearing loss. In addition to her 15 years as a parent-infant specialist with families of young children in the Seattle area, Katie was executive director of Whatcom Center for Early Learning, a birth-to-three program for children with special needs, from 2001-2004. She is currently a state-wide coach with Washington Sensory Disabilities Services (WSDS), providing support for families and service providers using the SKI HI Curriculum for a range of issues relating to hearing loss.

Richard Weleber, MD, PhD
Oregon Health & Science University

Dr. Weleber is double-boarded in ophthalmology and medical genetics, and heads the division of Ophthalmic Genetics at Oregon Health & Science University. He specializes in inherited retinal and macular dystrophies. His research interests include retinitis pigmentosa and allied disorders, electrophysiology of the eye and visual system, congenital anomalies, dysmorphology, and genetic and metabolic disease of the eye and visual system. He has pioneered the development of novel measures for testing retinal disease using the electroretinogram (ERG) and visual field analyzers, and works closely with the National Eye Institute, the Foundation Fighting Blindness, and pharmaceutical companies to validation testing strategies as endpoints for clinical trials for retinal degenerations.

Monday, June 7, 2010

All You Need to Know About the Usher Syndrome and Related Disorders Conference, Part I: Potential Therapies

by Mark Dunning

Valencia, Spain is beautiful. I have to confess with my America centric view of the world I knew nothing about Valencia, outside of their football club. Incredible architecture, parks, beaches, and food. Wonderful place. The conference was held in La Ciudad de las Artes y las Ciencias (The city of arts and sciences) in the auditorium of the Science building. It was a great facility for a conference.

The hosts, too, were wonderful. Dr. Jose Millan and his staff deserve a lot of credit for putting on such an event. It’s nice to know that Usher families have folks like them looking out for them.

The conference was enlightening and, at times, exciting. I’ll give you as brief a summary of the two and half days as I can, highlighting what you really need to know.

The conference was broken in to multiple sessions. I’ll go through the first session on the first day in this post then discuss the other sessions in later posts. This session was on potential therapies, which is probably of the most interest to this audience.

Clinical Trials for CNTF for Retinitis Pigmentosa
Paul Sieving, M.D., Ph.D.
National Eye Institute

We’ve known about neurotrophic factors (of which CNTF is one) for a while. These compounds seem to keep the cells in the eye from degenerating. However, targeting therapeutic compounds to the eye is a tricky business, as there is a barrier between the blood and the retina that prevents most molecules from entering retinal cells.. You can’t just take a shot in the arm, like with a vaccine, and necessarily have the treatment reach the retinal cells. So CNTF has been put in to this kind of capsule that can be put in to the eye via minor surgery. The capsule then releases the CNTF over time.

They have begun phase I clinical trials and Dr. Sieving presented the preliminary results. Ten patients were involved in the study. Five got a limited dose of CNTF and five got a higher dose. All patients in the trial had very limited vision. Not all of them had Usher syndrome but there were Usher syndrome type II patients in the study.

The results are still being collected and analyzed, but it seems like it helped improve the vision in at least some of the patients, who were able to read more letters on an eye chart after the treatment.

Why you care

This is about as exciting as the science of Usher gets. This is a potential treatment for the vision component of Usher syndrome that is in clinical trials right now and has demonstrated, at least initially, that it might help. There are still more phases to go before this is available as a treatment, but it’s promising enough that the Director of NEI wanted to talk about it.

Neuroprotective Effects of TUDCA and Safranal
Nicolas Cuenca
University of Alicante, Spain

Like CNTF, TUDCA and safranal both seem to have the ability to protect photoreceptor cells from degenerating. TUDCA is bear bile and has been used in traditional Chinese medicine as a treatment for eye and liver disease for centuries. Safranal is the stuff that turns rice yellow in paella (can you tell I was just in Spain?). Dr. Cuenca has found that treatment with TUDCA and safranal has slowed cell death in rat’s with retinal degeneration.

Why you care

This, too, is pretty exciting stuff. The research is farther away from helping families than the CNTF research and the doses used in the study were very, very high. Much higher than you’d want to take. But it did help. More studies need to be done, but it’s promising. However, until more studies are done, please don’t stuff yourself or your kid full of TUDCA. We don’t know enough about it. You might want to think about adding some more yellow rice to your diet, however. Any excuse to eat more paella is good with me.

The Use of Aminoglycosides as a Therapy for Usher Syndrome
Tamar Ben-Yosef
Technion-Isreal Institute of Technology, Haifa, Israel

Let me see if I can do this topic justice. Usher syndrome is caused by mutations in DNA. DNA contains the instructions on how to build certain proteins. If the instructions are wrong, you get a bad protein and cells don’t work properly. There are different ways to screw up instructions (just ask my wife when she sends me to the grocery store). One particular type of mutation is called a nonsense mutation. Basically these are periods in a sentence where they shouldn’t be. So when my wife says ‘pick up milk and bread PERIOD’ I hear ‘pick up milk PERIOD’ and screw up the instructions.

Aminoglycosides are drugs that allow a ‘read through’ of that misplaced period, hopefully allowing the full instructions on how to build a particular protein to be read.

There are some aminoglycosides that are commercially available today. The problem is that they are often toxic at the levels necessary to get the desired read-through result. Dr. Ben-Yosef has found some compounds that are more effective in getting a read through effect while reducing the toxicity. Unfortunately at the moment none of these compounds seem to work with nonsense mutations in Usher.

Why you care

If you or your family member has a nonsense mutation, you care a lot. This has the potential to treat your Usher syndrome by simply taking a pill. However, this is still in the theory stage. It hasn’t even helped treat Usher in an animal model yet.

Gene Therapy for Usher syndrome Type 1B
David Williams
Jules Stein Eye Institute, UCLA School of Medicine

Jennifer has explained gene therapy much better than I can here and here.  Just to give a quick synopsis, gene therapy is the act of overriding bad instructions within DNA by supplying a new set of good instructions. So going back to my wife example, she could override the entire bad instruction of ‘go sit on the couch and watch TV’ with the good string ‘go downstairs and do the laundry’.

This is accomplished by using a virus to ‘infect’ the cells with the new DNA. The problem is that different genes are different sizes and viruses are like airplanes in that they have a limited payload that they can carry. There are also only a limited number of viruses that can be used in gene therapy. The virus has to be safe and not cause other problems.

One virus known to be safe is the HIV-1 lentivirus. Dr. Williams and his team have found that this virus can be stuffed with a good copy of the MYO7-A gene that causes Usher type 1b and that it can deliver that gene to cells.

Why you care

I care a lot because my daughter has type 1B.  This proves that a safe virus can be used to deliver a good copy of the type 1B gene. This is an important step in moving toward clinical trials. In fact, there aren’t too many more steps before we get there. Right now the hope is that Phase I clinical trials will begin in mid-2011. By the way, this estimated date was not discussed at this conference but comes from a discussion had with Dr. Stephen Rose in a Coalition for Usher Syndrome Conference Call a while back.  In other words, don't write it in your calendar just yet.

USH1C Therapy Strategies in the Retina
Kerstin Nagel-Wolfrum
Johannes Gutenberg University of Mainz, Germany

The two previous subjects, those of aminoglycosides and gene therapy, were both discussed in this session as potential therapies for Usher type 1C. Preliminary data show that the gene can be delivered via a virus, which is good news for gene therapy as an option. Also 20% of all Usher cases are nonsense mutations and a particular aminoglycoside called PTC124 seemed to show promise in clinical trials for non-eye diseases.

Why you care

This is similarly good news for Usher 1C patients. While no particular date for clinical trials of gene therapy for Usher 1C were discussed, things are looking as promising for gene therapy in type 1C as they are for type 1B. On the aminoglycoside front, this just reiterated much of what Dr. Ben-Yosef had said but with a focus on Usher 1C.

Stem Cell Therapy for Usher 2a
Peter Francis
Casey Eye Institute, Oregon


Jennifer discussed Stem Cell Therapy and this particular study at length in a previous post, so I won’t go in to detail about it. A quick summary, though, is that stem cell therapy is the method of taking stem cells, essentially baby cells that could grow in to any other type of cell, and getting them to grow in to a healthy cell, in this case photoreceptor cells for Usher type 2A.

Two interesting things came up in this discussion. The first was that they have developed a way to test the vision in mice with Usher 2a and those tests have revealed vision loss in the mice. This is significant because historically we’ve had a hard time developing a mouse model that displays the vision loss phenotype. Dr. Francis found that the mice were losing their vision prior to any noticeable loss of photoreceptors. This is good news for testing potential treatments.

Those tests found that the mice treated with stem cell therapy had little functional deterioration of their vision during the ten week test period.

Why you care

This is great news for two reasons. First, a functional mouse model is critical to testing treatments and we hadn’t really had one before. These tests could potentially be used with other Usher mouse models as well.  Second, the stem cell treatment seemed to work, at least in mice. No schedule for clinical trials was discussed, but this was an important step in the process. It’s also important for other types of Usher syndrome which may also be treated in the same manner some day. Stem cells are the best bet for reversing vision loss in the long run, though, obviously, that’s a long way off.

Gene Therapy in Usher Syndrome Type 3
Eeva-Marja Sankila
University of Helsinki, Finland

More gene therapy, this time for Usher type 3. As with Type 1B and Type 1C, it appears that Usher Type 3 genes can be delivered via a virus.

Why you care

Same as we discussed earlier. This is good news for using gene therapy as a treatment for Usher Type 3. Again, no dates for potential clinical trials were discussed.

Most of the morning of the first day was exciting news for families with Usher syndrome. I will caution our readers once again, though, that wheels of science turn slowly. There will be more of these every other year science conferences before any of these are regularly administered treatments for families with Usher. That said, we are definitely headed in the right direction and, as you’ll read in the next post about the psychosocial aspects of Usher syndrome, the treatments are coming none too soon.

Thursday, June 3, 2010

More Gas for the Fire

by Mark Dunning

Editor’s note: This is a planned public debate between Mark Dunning and Jennifer Phillips, the two primary contributors to this blog. The ideas expressed in the posts during this debate will be purposely provocative and unfinished to invite a response from the other party. We hope you find the discussion valuable.

“You Can’t Handle the Truth!” – Jack Nicholson as Colonel Nathan Jessup in ‘A Few Good Men’

Sorry I’m late in responding to Jennifer, but I was over in Spain at the Usher Syndrome and Related Diseases symposium. You know what? Jennifer was right. The researchers DO talk to each other. They use big words and often seem to be speaking a different language, but they do actually talk to each other. More than that, they seemed really excited to share information. In fact, there were a number of presentations that thanked our dear Dr. Phillips for her assistance. But here is where the aforementioned dear Dr. Phillips misunderstood my original post. I merely said that researchers give the impression that they don’t talk to each other. So why do families with Usher syndrome have this impression?

The Researchers Are Too Distant From Their Real Purpose

I was one of only two parents at the conference. The other was a researcher. He was there in a professional capacity because, and this could be a whole posting on its own, he happened to be working in the field when his daughter was diagnosed with Usher. There were a couple of adults with Usher there as well, but again they were both professionals working in deaf blind programs in their home countries. So few families actually saw what was going on or heard any of the presentations.

The information was also brutally technical and scientific (protein structures, Jennifer?). This was exacerbated by the fact that many of the researchers used English as a second language. (A quick side note: It was truly amazing to hear these folks talk coherently about extremely technical topics in their second language when I had a hard time ordering dinner in Spanish. There are smart people working on Usher syndrome.) Further there were no interpreters or CART present at the event, so anyone with hearing loss would have had a hard time even accessing the dense information being presented.

None of this is meant as a criticism of the organizers of the event, who were fantastic, but rather to point out that families with Usher syndrome often felt very distant from the discussions. The researchers were very enthusiastic about their mice and their protein chains and their alleles, but very few seemed outwardly cognizant of the fact that those were a means to an end and that we, the families with Usher syndrome, were that end. To the everlasting credit of the organizers, they did an excellent job of including sociologists, behavioral studies, and social workers among the presenters to try to tether the scientists to the patients, but the researchers often got the same glassy look in their eyes when social data was discussed that I got when any study Jennifer was involved in came up (Sorry Jennifer. I really did try.)

Let me pause here for a moment to make clear it is NOT that the researchers don’t care about families. They were all appropriately appalled by the social data, especially the suicide rate (frighteningly high). Indeed, when my daughter showed up at one coffee break, they were all thrilled to see her, many commenting on how important it was that they be reminded she and others like her are the reason that the function of the whirlin protein matters at all. But I got the sense that a child with Usher was a rarity in their lives when, in truth, they probably should all have a picture of a patient with Usher taped above their door. In the end, the families are all that matter. Even if you were an empty hearted researcher you would have to recognize that without Usher families, you don’t have a job. No one cares about developing an Usher syndrome animal model if no one has Usher syndrome.

The Researchers Aren’t the Only Ones That Need the Information Presented

I agree with Jennifer that the media doesn’t do a good job with science content, but I’m not asking that the conference be broadcast on C-SPAN. I only want some thought given to how to communicate the news of the conference to families. This is not a criticism of this conference (again, our hosts were wonderful) but of these scientific conferences in general. I know you can go to the ARVO web site and find abstracts on the conference and I know that if you were to contact the organizers of the conference in Spain that they would happily share the information with you. All of that assumes, of course, that you knew these conferences were happening. But how would the average family know that?

Further, what, exactly, would they read? Here’s a sample e-poster available from the ARVO conference.

Um, yeah.

The point is that not only does there need to be some way to dumb down this information and pass it on to families, that should be one of the priorities.

Information is NOT Freely Shared by Everyone

And that leaves me flummoxed most of the time, downright angry at others. Let’s start with flummoxed. I was at the conference in Spain and heard the talks. The abstracts are printed in the book I took home. I want to communicate out the contents of the presentations I saw to other families. But I’m nervous because I don’t know what the researchers consider privileged information and what they don’t. In other words, even though I heard it and know it could help families, I might upset some folks if I share it. That frustrates families. It is research for us. Heck, it’s often research about us and yet we’re not allowed to know it? How can that be?

One doctor presented a database of genetic information that she had created. The idea was to share genetic discoveries about Usher syndrome with the wider researcher community. Awesome idea. But researchers could enter their findings and mark it private if they so chose. The doctor strongly urged people not to do this, but the fact that she felt it was necessary to include such a feature to get other researchers to use the database speaks volumes about the mindset of many. It is their discovery, their research, and the rest of the research community and the families themselves are not welcome to it.

That makes me angry. Not only could they possibly be withholding information that could help my family but they may very well be stunting the research done by others in the process, further slowing the overall search for a cure.

We CAN Handle The Truth

I understand the concern around sharing certain information with families. I feel it now as I prepare to write about what I learned at the conference. I learned, for instance, that if you shoot a rat with retinitis pigmentosa full of so much TUDCA that the rat eventually dies from the dosage, that rat’s vision does not deteriorate while the vision in similar rat’s with RP does deteriorate. I am worried that parents will buy an oil drum full of TUDCA and hook it via IV to their infant. But does that mean that families shouldn’t be told that TUDCA has protected the vision of rats with RP in monstrous doses. I mean, I’m a parent and I’m not going to be shooting up my daughter with the stuff.

I only felt compelled to speak up once during the meeting. That was when a debate opened up about the merits of withholding or delaying the delivery of a diagnosis to families found through the newborn hearing screen. The idea was to ‘protect’ them from the emotional trauma of an Usher diagnosis so soon after they receive a hearing loss diagnosis. My response was something along the lines of ‘Parents are adults. Treat them like adults.’

The point here, to misquote Jack Nicholson, is we CAN handle the truth. Please, please, please don’t protect me from information because you don’t think I’m big enough to handle it. If a doctor or a researcher I respect tells me to please, whatever you do, don’t stuff your kid full of TUDCA, I’m not going to do it (and please, whatever you do, don’t stuff your kid full of TUDCA). However, if you want my respect, you’ll tell me all you know and trust that I can handle it.

The Big Problem

More than once I talked to doctors who lamented the fact that desperate patients had ignored their advice and gone to Cuba or China to have some cockamamie treatment ‘guaranteed’ to save theirs or their child’s vision. They were understandably appalled by this and I could see that it drove their fear of mentioning any untested treatment (like TUDCA) to any family. They don’t want desperate, frightened families to do something rash. They are right. We don’t want that to happen.

But when doctors and researchers always stress what we don’t know while not openly sharing what we do, it opens the door for these scam artists to step in. What doctors fail to realize is that they contribute to the problem when they withhold information from families. It makes them seem ill informed. (You mean you hadn’t heard that TUDCA helped rats see better?) It also understates what we do know and exaggerates the possibility that Jennifer’s hated ‘pseudo-science’ could hold merit. I mean, they laughed at Columbus when he said the world was round, didn’t they? That, in turn, makes families wonder if maybe, just maybe, those doctors in Cuba know a little bit more or the doctors in China are a little more open to sharing information.

This is about trust, and trust starts with the open sharing of information. Tell me what you know in a format I can understand. I can handle the truth.