FRR Visions
The newsletter for families and supporters of the Foundation for Retinal Research
http://www.tfrr.org/ • info@tffr.org • 1-224-927-5063 Sally Lewinski, editor
Gene therapy for LCA shows promise
National Eye Institute
Two groups of investigators have reported independently on their initial observations from Phase I clinical trials of gene transfer for Leber congenital amaurosis (LCA) caused by mutations in the RPE65 gene. The two papers appear in the April 27, 2008, online version of the New England Journal of Medicine. A third Phase I clinical trial, one supported directly by the National Eye Institute (NEI) of the National Institutes of Health (NIH), is ongoing, but initial observations have yet to be published. These Phase I clinical trials are designed as a preliminary assessment of the safety of gene transfer techniques in treating people with LCA.
People with LCA are born with severe visual impairment or develop vision loss early in childhood. "Proof-of-concept" studies in animal models of LCA demonstrated gene transfer techniques to be safe, effective, and long-lasting in restoring visual function. NEI has supported much of the basic, translational, and pre-clinical research leading up to these Phase I trials. For extensive background information on gene transfer and LCA, go to: http://www.nei.nih.gov/lca/.
The initial observations indicate that within a short follow-up period, five months to one year, gene transfer for LCA appears to be well-tolerated and safe. Phase I clinical trials are specifically designed to evaluate safety; they do not feature the standard statistical and methodological safeguards required to properly evaluate treatment
effectiveness. Nonetheless, several of the reported observations suggest that gene transfer may be exerting modest effects in some of the treated individuals. Additional follow-up testing of the treated individuals should determine whether these effects are sustained. Durability of effects is crucial given the history of human gene therapy trials which have demonstrated that early gene expression can be thwarted by immunologic or other responses.
No conclusions can be made at present as to whether gene transfer will restore visual function in people with LCA or impede further progression of the disease. Additional important insights will be gained when investigators have the opportunity to examine the totality of the published data, including observations from the third Phase I clinical trial. These insights will enable investigators to refine the gene transfer techniques and will provide the preliminary information needed to design the Phase II and Phase III clinical trials that are necessary to determine both safety and effectiveness in a rigorous way.
Family to Family
By Dave Bushland
Mary Rose Bushland likes playing peek-a-boo. “We throw a blanket over her, and she goes ‘peek-a-boo!’” her father, Dave Bushland, of Bella Vista, Ark. said. By all measures, this is an activity that would excite most 2-year-olds. But Mary Rose was diagnosed with LCA at four months, and her lack of vision means that a simple childhood game like peek-a-boo is different for her than it is for other children.
Mary Rose wears glasses, but Bushland said those serve more to protect her eyes. Children with LCA tend to press on their eyes, he said, and Mary Rose’s lack of sight means her reflexes won’t react to shield her from flying objects.
“We were hoping that as she gets older she’d have some sort of light/dark perception,” Bushland said. “But we think she’s totally blind.”
One of the hurdles the Bushland family faced when Mary Rose was diagnosed was a dearth of resources for parents of visually impaired children. A Web site, Family Connect, was recently launched through a partnership between the American Foundation for the Blind and the National Association for Parents of Children with Visual Impairments. The Web site aims to provide much-needed resources and networking opportunities for parents.
When Mary Rose was first diagnosed, the Bushlands didn’t have any way to reach out to other parents of children with LCA. “We were alone. There were no other resources,” Bushland said. “It’s so important to have that networking.”
The LCA Family Conference is July 24-26 at the Cleveland Clinic’s Cole Eye Institute.
This Conference is a unique opportunity to learn first hand the most current information on LCA directly from the researchers and doctors who are working on it. This is a wonderful chance to bring your list of questions, and your families’ lists of questions and get straight answers. We will also be offering medical exams, ERGs and retinal photographs through the Cole Eye Institute on Thursday, July 24 and Friday, July 25. You must fill out the medical request sheet and return it promptly as space is limited. Visit http://www.tfrr.org/ often to get updates on the conference.
Grandfather-to-Grandfather
By Alan Schwartz
Ten years ago, in the very early days of learning that my youngest grandson and namesake Alan Brint had LCA, my wife Ronnie and I accompanied our daughter Betsy and son-in-law David to various medical centers in search of answers to our questions about LCA.
While meeting with researchers at the University of Pennsylvania, I met a grandfather, Jack Brier, of similar age to mine and with a grandson, Daniel Matzkin, who had LCA. We bonded almost immediately. Jack was outgoing, incredibly approachable, keenly alert and a generous contributor to LCA research and clearly had a great love for and major involvement in the life of his grandson.
Daniel was already eleven when Jack and I met. Jack sensed how apprehensive I was as to Alan’s future and he intuitively understood the stages my family and I were going through and would go through as we came to grips with the realities to be faced. Jack shared with me how close he and Daniel had become…..buddies who had bridged the two generation gap. Jack told me of many days and nights he and Daniel had spent together and the movies they had gone to where Jack whispered to Daniel important visual aspects of the film that were pertinent to appreciating the movie.
We mutually agreed to keep in touch and for our families to meet when Alan was a bit older. He wanted us to see for ourselves how beautifully Daniel had developed; how well his family had adjusted and he wanted Daniel to talk to Alan.
That meeting between families did take place in Florida several years later. By then, Daniel was doing karate and was getting “A”s in regular school. WOW.
Jack and I continue to keep in touch with each other to share proudly the ever increasing successes of our respective grandsons. Daniel is presently in his second year at Michigan law school and has offers from top flight law firms for summer internships. Alan is in regular fifth grade, has a gift for math, is computer literate and enjoys learning and playing classical piano, swimming competitively and recently earned his purple belt in karate.
I look forward to future calls with Jack as we exchange stories of our respective grandsons and follow and rejoice in their development.
Apple Pie and Peter
Betsy's Corner
Everyone needs a Peter Tucic in his or her life. If you are coming to the 2008 LCA Family Conference you will get a chance to meet Peter and know what I am talking about. Peter is a 19-year-old “dude” (and when you meet him you will know why I call him a “dude”) with LCA. For years Peter has been teaching Nicki Purpura (LCA age 9) braille music, and every so often Nicki’s mother, Amber, would call me to sing the praises of Peter and tell me that I must bring Alan (LCA age 11) out to meet him. After much prodding, I trekked with Alan out to Lisle, Illinois and that is where I fell in love.
Peter is smart, funny, handsome, patient, independent, talented and so much more. But the bottom line is Peter is cool. When Alan first met Peter, Alan began jumping around and flapping his hands a bit in excitement. Peter calmly placed a hand on Alan’s shoulder and with a crooked little smile he said, “Whoa, Dude, calm down. Chill a bit and let’s just chat.” Alan thought that was about the funniest thing he had ever heard, and without a fuss Alan calmly sat, faced Peter and ”just chatted” for about an hour.
Since that meeting, Peter has been coming out to our house on a weekly basis. We meet him at the train (Alan is motivated to be more independent because of this), and the two boys spend a few hours together. They talk about everything from music to sports. Each week they have a project to do like making a bed or folding a basket of laundry. Peter growls at me when I try to do too much for Alan and encourages Alan to want to do more on his own.
Last week they made an apple pie together. Peter showed Alan how to peel and slice the apple. I watched in fear as the two of them worked with the chef’s knives – but they did it. No fingers were lost. Dishes were done. And, I am sure that was the best darn apple pie Alan ever ate. I know it was for me.
Thank you Peter.
— Betsy Brint
David Brint receives FFB award
The Foundation Fighting Blindness has awarded its “Builder of Sight Award” to David Brint, co-founder of the Foundation for Retinal Research.
David became a FFB National Trustee in 2000, and joined the Foundation’s National Neurovision Research Institute Board in 2004. Later, he joined the FFB’s Board of Directors and is currently the Vice President of the FFB Board. He also co-chairs the Science Liaison Committee.
FFB Chairman Gordon Gund presented David with his award at a recent FFB dinner to honor his hard work in fighting blindness.
Amazing Grace
By Ronnie Schwartz
May 20, 1997, was a very important day in the lives of two families, the Amodeos of Dunellen, N.J. and the Brints of Highland Park, IL. On that same spring day when baby Grace was born to Wendy and Joe Amodeo, Alan, the 2-month-old son of Betsy and David Brint, was diagnosed with LCA. Thus began the crossing of two lives and two families, whose dedication to the purpose of finding answers led one family to establish, the other to support, the then newly formed FRR which has since brought them and so many other LCA families together.
Almost as soon as Betsy and David created the FRR web site, it was discovered by Grace’s father Joe Amodeo, and soon thereafter several donations to FRR began trickling in from New Jersey. They were not it turns out, from families of LCA patients, but from the customers of Joe's mom, Carmella Amodeo. Carmella is a dressmaker in her hometown of South Plainfield, N.J. Wanting to do something to help Grace, she asked her husband Tony to print up small forms for donations with envelopes addressed to FRR. When Carmella’s customers wanted to leave a tip, they picked up the envelopes next to the sewing machine. There must be many satisfied and loyal customers of Carmella Amodeo, as the donations in honor of Grace have been coming in for over nine years.
Skip ahead to May, 2008. We find Grace Amodeo now eleven years old, a straight A student on the honor roll, a former Brownie now graduated to a Girl Scout, a two-week overnight camper and an avid swimmer. Grace exercises on the trampoline, likes gym class, and enjoys walking and running with her dog. She, like Alan Brint, enjoys reading Braille and both are very musical. Alan plays classical piano and is learning to read Braille music; Grace sings in the choir, and plays the flute in addition to the piano. Grace became interested in the piano at age 2 when her mom, Wendy, took her to visit her grandmother’s nursing home where Grace discovered a toy piano. She played right away and showed so much talent that a teacher who heard her play now fits her in on Saturdays when there is a cancellation - at no charge!
Both Grace and Alan are learning Hebrew to prepare for their Bat and Bar Mitzvahs - and we are sure the two will enjoy comparing notes (probably in English) on their busy lives when they meet again at the FRR Conference in July.
FRR would like to publicly say THANK YOU to all the customers of Carmella Amodeo who have honored Grace with their many donations; and kudos to Grace's parents and grandparents Wendy, Joe, Carmella and Tony for helping Grace meet her challenges, and especially to Grace for fulfilling her family’s dreams so “gracefully.”
our vision is clear
Students perform well at "Illinois Braille Challenge"
By Barbara Perkis
The Illinois Instructional Materials Center (IIMC) hosted the first Illinois Braille Challenge at The Chicago Lighthouse on Saturday, February 23, 2008. The Braille Challenge, a national program of the Braille Institute in Los Angeles, consists of a two-stage academic competition designed to motivate school-age braille readers to excel in this vital medium.
A total of 28 students in grades 1-12 registered for the February event. There were even four students from downstate Illinois, making this truly an “All-Illinois” Braille Challenge. The IIMC has a total of 255 students who read braille. 182 students use braille as their primary reading medium and another 73 use braille as a secondary reading medium.
Presenting sponsor of the Illinois Braille Challenge was the McCormick Tribune Foundation. National sponsors were Freedom Scientific, Seedlings Braille Books for Children and Perkins Products at Perkins School for the Blind.
The contest is divided into five academic levels. The levels are Apprentice level grades 1-2, Freshman level grades 3-4, Sophomore level grades 5-6, Junior Varsity level grades 7-9, and Varsity level grades 10-12. Contest categories for each level are, Apprentice and Freshman: spelling, reading speed - comprehension and proofreading; for Sophomore: reading speed - comprehension, proofreading, spelling and speed - accuracy; for Junior Varsity and Varsity: reading speed - comprehension, proofreading, speed - accuracy, charts and graphs.
This daylong event offered a wonderful experience for students and their families to participate in literacy activities and meet other visually impaired peers from all over Illinois. Nearly 150 people attended. The crowd included the contestants, their families, teachers of the visually impaired (who served as contest proctors), braille transcribers (who scored the contests), volunteers and staff. Informative programming for parents who attended was provided by Illinois Parents of the Visually Impaired. Activities for attendees siblings were provided by staff of the Center for Child Development. Highlighting the day-long event was a Mardi Gras theme topped off by performances from the Midway Ramblers (a Cajun band), door prizes, and a wide variety of tasty food and treats.
The ten Illinois winners, 1st and 2nd place for each of the five academic levels, took home prize money ranging from $50 to $500 and may be eligible to participate in the National Braille Challenge scheduled to be held June 27-28 in Los Angeles.
They are: Jack Falejczyk of Elk Grove Village won 1st place honors and Miguel Orduno of Carpentersville won 2nd place honors in the Apprentice category; Alyssa Townsend of Lake Zurich won 1st place honors and Nicki Purpura of Naperville won 2nd place honors in the Freshman category; Hannah Hakes of Naperville won 1st place honors and Jessica Minneci of Naperville won 2nd place honors in the Sophomore category; Alexa Schwichow of McHenry won 1st place honors and Preston Radtke of Arlington Heights won 2nd place in the Junior Varsity category; Rayette Rucker of Metropolis won 1st place honors and Adnana Saric of Chicago won 2nd place in the Varsity category.
The contestants who will compete for the National Braille Challenge were announced on May 1, 2008.
Have you heard...
The Foundation for Retinal Research has joined as a National Partner on the new website http://www.familyconnect.org/. The goal for this site is to provide useful information, support and resources, all specifically geared to parents and families of children with visual impairments. The FRR has an LCA page on FamilyConnect where you can find information on subjects relating to LCA such as the most current updates on the Gene Therapy Clinical Trials at The Children's Hospital of Philadelphia.
FamilyConnect is brought to you by: AFB (American Foundation for the Blind) and NAPVI (National Association for Parents of Children with Visual Impairments) and was launched publicly the week of April 29 with a major media campaign. We hope you will visit this new website often.
Have you heard...
The Grousbeck Family Foundation has donated $25,000 to help support the 2008 LCA Family Conference.
Clara's Cause
Greg Rudzinski's ride for LCA is in honor of Clara Johansen
I wanted to tell everyone about an incredible fundraiser that is going on right now and to let everyone know how to get involved. Clara’s Cause is an idea Greg Rudzinski came up with while touring around the Atlantic Provinces of Canada. He wanted to combine his passion for travel with a worthy cause. Clara’s Cause is about bringing awareness to Leber’s Congenital Amaurosis and getting the community involved.
Greg has known Clara’s parents, Mark and Laura Johansen for the last 11 years. As a newbie to Oregon, he was fortunate to meet Laura’s sister Holly. Holly always offered an invitation to spend the holidays with her family. He took her up on the invite and the next thing he new, he had four new sisters. Being 2,600 miles from home, it was nice to have a satellite family. Their generosity has provided for an enjoyable and comfortable stay. As he prepares to leave Portland, he would like to give back some of the generosity he has received.
Greg’s motorcycle journey across North America will be from Homer, Alaska to St. John’s, Newfoundland. He will travel through Alaska, one territory and nine provinces. There will be six checkpoints along this route. The six legs and distance are as follows:
• Homer, Alaska to Whitehorse, Yukon, 930 miles
• Whitehorse, Yukon to Grande Prairie, Alberta, 960 miles
• Grande Prairie, Alberta to Winnipeg, Manitoba, 1,100 miles
• Winnipeg, Manitoba to Sudbury, Ontario, 1,070 miles
• Sudbury, Ontario to Fredericton, New Brunswick, 930 miles
• Fredericton, New Brunswick to Ferry Terminal, 410 miles
• Ferry Terminal to St John’s, Newfoundland, 565 miles
The Ferry schedule varies from day to day so it is uncertain when he will depart for Newfoundland. The ferry ride takes 5.5 to 7 hours depending on the time of day and weather.
This journey is roughly 6000 miles across North America. He hopes to complete it in eight days, 750 miles a day. Due to road conditions, weather and other events, the trip could be prolonged. Follow the blog to get your updates.
Follow Rudy as he rides across North America from the furthest points west to east. You will have an opportunity to win prizes as he reaches check points along the way. Buy a $10 raffle ticket and have a chance to win up to $300.
Your raffle ticket represents a specific time. If your time coincides with the check point time, then you are a winner. Take a chance for a great cause and follow the adventure to find a cure. To buy tickets go to http://www.clarascause.org/
Artificial Vision: Sight Restoration Through the Retinal Prosthetic Device
Dr. Mark Humayun, MD, PhD; Professor of Ophthalmology, Biomedical Engineering, Cell and Neurobiology at Doheny Eye Institute at University of Southern California, Los Angeles
Dr. Jerry Chader, PhD; Professor of Ophthalmology and Chief Scientific Officer at Doheny Retina Institute, University of Southern California, Los Angeles, CA
Patients with Leber’s Congenital Amaurosis (LCA) usually have little useful vision from very early in life. Depending on the specific genetic mutation in the patient, retinal photoreceptor cells may rapidly degenerate and be lost or they may survive a longer time although in a dysfunctional state. In either condition though, a major question is “How can we restore functional vision to these patients – even in a situation when most or all photoreceptors are gone?” In cases where the photoreceptor cells are not present in older patients due to a long history of the degenerative disease or in young patients due to a rapid course of the disease, prospective treatments such as gene therapy or the use of neuron-survival agents will be little or no use.
One possibility for restored vision is to replace the dead or dysfunctional photoreceptor cells with an electronic device that will essentially perform a function similar to the natural photoreceptors, i.e., capture an external image and pass it down the optic nerve to the brain for final synthesis of a visual picture. This is a simple concept but one that is very difficult to functionalize. Significant problems need to be overcome in a number of research areas such as electronics, miniaturization and packaging. The electrical signal of the device must be strong enough to properly stimulate the retina but not damage it. Also, the portion of the device that is implanted on the retina must be appropriately small such that it fits within the intraocular confines. The delicate electronics must also be properly packaged such that they are not damaged by the relatively warm saline environment present within the eye. In particular, the device must be designed such that it does not damage the delicate retina to which it is attached. Both electrical and mechanical damage must be minimized or obviated such that the device can function for the lifetime of the patient. Most of these problems have now been overcome such that Clinical Trials are in progress in patients with Retinitis Pigmentosa (RP).
How does the device work? An external video camera is placed behind glasses on the patient’s nose. This camera captures an image and passes it to a special computer for processing. From the computer, an electronic signal is then passed to an electrode array implanted directly on the retina; the array consists of a number of tiny individual electrodes. These electrodes transfer the visual information to the underlying cells of the retina, imparting the visual information to the remaining, non-photoreceptor cells. These cells begin the processing of the signal and pass the information down the optic nerve to the brain. In the brain, the signal is further processed and synthesized into a final visual image. However, this basic design can have many variations. There are a number of excellent groups of investigators around the world with somewhat different approaches to the device. One main difference, for example, is whether the device will be “epiretinal” or subretinal”. An epiretinal device is implanted on the front surface of the retina, essentially impinging on the ganglion cells whereas a subretinal device is implanted in the space behind the retina previously populated by photoreceptor cells.
Using these different designs, groups in Germany and in the USA have begun human testing of their devices. To get to this point though, significant funding has been required. Groups in Germany, for example, have been heavily supported by the German government. Our group at the Doheny Eye Institute of the University of Southern California (USC) has had competitive grant funding from the US Department of Energy, the National Science Foundation and the National Institutes of Health. Critical funding has also come from the Foundation for Retinal Research. Company liaisons are also needed, especially in moving to clinical trials. For example, I collaborate with Second Sight Medical Products (SSMP) which is conducting an FDA-approved clinical trial (called Argus 1) of the prosthetic device I have worked on now for over two decades. In the initial stage of the trial (Phase 1, safety phase) started in 2002, six patients were implanted with a first-generation device that had 16 electrodes on the “chip” implanted on the retina. All patients had advanced RP and had bare or no light perception (i.e., completely blind). Patient safety of the device in this phase of the trial was demonstrated and there were no device failures. Surprisingly though, some efficacy was seen as well. Importantly, light perception was restored in all patients. Moreover, patients had restoration of some object recognition. For example, scanning with the device allowed patients to discern between objects such as a plate and a cup. Although slow and laborious, this was a marked improvement in vision over the complete blindness of the patient prior to the implantation of the device. Testing continues with these patients with further improvements noted such as in mobility.
Later last year, Phase 2 of the clinical trial (called Argus 2) began with the implantation of second-generation devices in patients at several sites around the world. The new device is smaller than the older device, easier to implant and has 60 electrodes touching retina. Theoretically, the larger number of electrodes will give much improved vision to the patients compared to the Argus 1 model. Although it is yet too early to assess the effects of the Argus 2, we have high hopes as to both safety and efficacy of the device.
What does the future hold for retinal prosthetic implants? As mentioned, above, many excellent groups are currently working on their versions of the device with some groups already doing patient testing. With our device, we now have a new prototypic model containing hundreds and ultimately thousands of electrodes that should allow for face recognition as well as the ability to read large type.
Thus, we believe that the future of Artificial Vision looks bright. Older patients with advanced LCA as well as younger patients with early, severe photoreceptor damage could very well be helped by the prosthetic implant with the return of functional vision. This could mean vastly improved mobility, reading ability, communication, independent living and a marked improvement in general Quality of Life.
Dear Friends:
The RPE 65 trials of which I suspect you are all aware, have reported excellent initial results. Restoring vision in a safe way is and hopefully will be truly one of the great accomplishments of this decade. In all of our jubilation I want to make sure we keep everything in perspective. First, the current trials for RPE 65 are safety trials which means they are designed to make sure the vector does not cause problems. Future phase of the trial will test dosage and will test a larger population. The final trial will not be complete for at least four years, after which the FDA will hopefully approve its use for affected people. Second, we are hopeful that other retinal genes will qualify for and complete preliminary work to prepare for gene therapy trials, which will also take time. Every individual gene will need some testing before they will be able to proceed with gene therapy. Hopefully, with the success of the RPE 65 trial and others, the work required for each individual gene therapy to proceed will be reduced, but each will need a specific program and major resources.
Gene therapy is a possible method for either restoring some vision or halting vision deterioration for people who have photoreceptors. If an individual’s photoreceptors are gone or unable to function, then replacement therapy or visual prosthetics will likely be the most viable option to restore vision. Current technology using high resolution or ultra fast OCT scans can tell if photoreceptors exist. At the Cleveland conference we will try to have a list of the institutions that offer this technology so each of you can be tested.
At the FRR, we continue to aid the development and advancement of strategies for LCA genes that are candidates for gene therapy. We also support the work of individuals who are working on photoreceptor replacement and other therapies that may help keep photoreceptors alive until corrective therapies are found.
In summary, my long-winded message is that we are making progress. A decade ago this would have seemed like pipedreams. But today some dreams are becoming
realities. It will take time, strong commitment, major financial resources and maybe some occasional setbacks but we are moving in the right direction, due in large part to all of you who support the FRR and other organizations committed to helping bring vision and otherwise aiding those of us affected by retinal degenerative diseases.
This is a time to be excited, but still patient. See you in Cleveland! David Brint, Co-Founder of FRR
RESPECT FOR ALL PERSONS
Saint Mary's College of California
Skylar Covich believes the best way to pay back those who have made his scholarships possible is to get good grades. With a 3.7 grade point average, he is not only making donors proud but also paving the way toward his goal of becoming a college professor.
“My scholarships definitely enable me to come to Saint Mary’s and be fully involved here,” says Covich, who serves as president of the SMC Democrats Club and as a student member of the Core Curriculum Task Force.
It hasn’t been easy for him. The 20-year-old junior from Redding is blind and relies heavily on technology for his education. His computer has both Braille and voice recognition attachments, allowing him to take notes and read anything on the screen.
“Saint Mary’s has been a place where it has been easy for me to succeed,” says Covich, who has received a Francis Cullen Miller scholarship and other awards. “The small classes have let me get to know my professors quicker and allowed them to learn what my strengths are.”
Covich spends a lot of time with professors in the Politics Department, his major course of study. His biggest inspiration is Professor Hisham Ahmed, who is also blind and grew up in a Palestinian refugee camp.
“It’s more difficult being blind in that part of the world,” says Covich. “I have grown up with the technology, and the talking programs have gotten better and better.”
Acknowledging the close ties between politics and religion, particularly in the Middle East, Covich plans to minor in theology and religious studies.
“Religion is a really important part of the world,” he says. “It affects a lot of what happens in the world.”
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The Mission of the Foundation for Retinal Research is finding treatments
and cures for Retinal Degenerative Diseases and supporting affected families.
