THE ACHIEVER Retina Australia Victoria AUTUMN EDITION – MARCH 2011 ROSS HOUSE, 4TH FLOOR 247 - 251 FLINDERS LANE MELBOURNE VIC 3000 PHONE (03)9650 5088 FAX (03) 9639 0979 Email: support@retinavic.org.au Web site: www.retinavic.org.au INSIDE FROM THE PRESIDENT MESSAGE FROM NZ ADAPTIVE TECHNOLOGY REBATES FEATURES: VICTORIAN BLIND CRICKET BLIND DRIVER ON RACEWAY WHAT ARE ORPAH DRUGS? FUNDING BOOST RESEARCH UPDATE: RECENT DEVELOPMENT S IN RETINAL DEGENERATION CELEBRATING RARE DISEASES DAY PREVENTION OF AUTOSOMAL DOMINANT RP ORPHAN DRUG DESIGNATION CONE PRESERVING TREATMENT UNDERSTANDING STEM CELL THERAPY – PART THREE PLASTIC ARTIFICIAL RETINA BONE MARROW STEM CELL STUDY STEM CELL RESEARCH PROGRESS QUESTION TIME LAST WORD AUTUMN NEWS Play Blind Cricket! Focus on Orphan Drug Designations and Stem Cell Developments Local, Regional and International Content Beginning of article FROM THE PRESIDENT – Leighton Boyd It gives me a great deal of pleasure to write the introductory article for our newsletter, “The Achiever”. Once again our editor, and vice president, Rick Clarke has put together an issue which makes for compulsive reading. We are currently living in very exciting times with respect to the world of research and Rick has provided you with some of the latest accounts of work which is being undertaken in Australia and overseas. Also included are articles of general interest, I hope that you enjoy reading them as much as I did. End of article Beginning of article RETINA AUSTRALIA MEDIA RELEASE BLINDNESS PREVENTION CHIEF APPEALS FOR GOVERNMENT HELP Graeme Banks, president of Retina Australia, has appealed to Australia’s political leaders for assistance in establishing and developing patient registers. He says that without such registers potential treatments and cures for the estimated eight thousand Australians suffering inherited retinal diseases cannot be further developed. He says his organisation has already instigated an Inherited Retinal Disease Register and DNA bank in Western Australia aimed at having all people with an inherited retinal disease and their selected blood relatives provide a DNA sample so as to assist in the search for rogue genes. “This has been set up through the hard work of Retina Australia’s state organisations in raising the funds necessary for the project,” he says. “However, ongoing support from government and philanthropic sources is still needed to cover the significant cost of fully developing the register so as to be able to 'sequence’ the DNA samples for treatment purposes when gene therapies are available.” “With more projects reaching human clinical trial stage, patient involvement is more crucial than ever to the development of potential therapies. Further, we need patients, their families and other supporters to play their part in making sure successfully developed treatments are widely accessible to affected people.” Research is intensifying throughout the world in an effort to halt the progress of retinal dystrophies and find a treatment or cure. Mr Banks says that with leading researchers and clinicians at the helm of a number of successful vision and ophthalmology research projects, Retina Australia is confident that a cure or therapy for these conditions is within reach. In recent years more than 100 mutant genes have been identified as responsible for inherited degenerative loss of vision. Clinical trials have been conducted recently using drugs that inhibit the death of cells in the eye. “Clinical trials face major financial and legislative difficulties,” Graeme Banks says. “We appeal to the government to become involved in the process, from proper genetic diagnosis and genotyping through to the establishment of registries. The journey travelled by the international retinal research community to reach these exciting times has been a very long one. It is now time for patients, research funding authorities, health administrators and politicians to play their part in ensuring we reach our destination.” “Only by playing our part will we offset the huge emotional, social and economic effects of sight loss and blindness from diseases such as Macular Degeneration, Retinitis Pigmentosa, Usher's syndrome, Stargardt disease and others too numerous to mention.” This is an edited version of the media release by Robin Poke – President of Retina Australia (ACT). IRDR & DNA Bank Last week I am proud to say that we sent our third and final contribution of $39,961.20 to the Australian Inherited Retinal Disease Register and DNA Bank. This money has been raised through some very generous donations given by our members and friends, as well as through fundraising such as raffles and the sale of merchandise. Retina Australia Vic, together with our partner interstate Retina organisations, undertook to fund the IRDR & DNA project for three years, commencing 1st April 2009. Moves are currently under way to seek funding to enable the extension of the program for a further three years as from 1st April, 2012. The second three year phase will see the continued collection of DNA material (ie from newly diagnosed persons etc) but most importantly the sequencing of the DNA collected during the first three year phase. Although, over 2000 DNA samples have now been obtained, the research team in WA were aiming for 3000 DNA samples during the three year period. Many of you have responded to the call for participation in this exciting research initiative, but if you haven’t, it is not too late. Please contact the office on 9650 5088, or by email at support@retinavic.org.au and we will gladly send you the Expression of Interest Form and talk to you about what is involved in the process. The current funding from Retina Australia, covers all costs for program participants except the cost of travel to and from your local pathologist. VICTORIAN RESEARCH In the previous Achiever, I reported that Retina Australia had funded three research teams for 2011 and outlined their research projects. I am delighted to be able to announce that in addition to the $139,700 allocated for research late last year, Dr Erica Fletcher and her team have been awarded a grant of $40,000 so that they can continue their search for treatments for inherited retinal diseases. Dr Fletcher’s research, which commenced in 2010, is developing an understanding of how photoreceptors die in order to develop therapeutic agents that will slow the progression of Retinitis Pigmentosa. Members who were able to attend our AGM last October were provided with a snapshot of the progress being made by this research team from Dr Fletcher herself and we look forward to hearing details of further results in due course. GRAEME CLARK ORATION I was invited by Bionic Vision Australia to be their guest at the Graeme Clark Oration and Dinner which was held on Wednesday 9 March. The Oration was given by Professor Terrence J. Sejnowski Ph.D. who is a world renowned professor of biology and neuroscience from the University of California. The oration, or lecture, captured the essence of the research world connecting biology, engineering and computing for the sharing of ideas and exciting developments and innovations which together these multi-disciplinary teams are creating. It was extremely exciting to be a part of this evening which discussed the workings of the brain and had some direct implications for the underlying concepts behind the development of the bionic eye. I am sure that during the next two years we will hear more about this work. BOARD & STAFF CHANGES It is with regret that I announce that Justin Marshall, who has served as a member of the Board for in excess of two years has tended his resignation. Justin has been suffering from a debilitating back injury for some time and consequently needs to devote more time to his recovery. On behalf of all members I would like to thank him for his significant contribution to the work of Retina Vic during his time on the Board and to wish him well for the future. We hope that it won’t be long before he has fully recovered. Consequently we are seeking a replacement member for the Board to assist us with our work. If you are interested in joining the Board, or in finding out about what might be required, please do not hesitate to give me a call on 0417 566 899 to discuss. The Board currently meets every second month, on a Tuesday evening, and at other times by phone conversation. I look forward to hearing from interested members. We have also had a change in our Office and I would like to welcome Kristen Xing who has taken over from Lin Sun as our Financial and Administrative Officer. Kristen will be in the Office every Tuesday and Thursday between 9.30am and 2.30pm. Lin was an excellent addition to our organisation and provided great support to myself and all members during the two years of her employment. She was given the opportunity to work full time with an organisation who is our neighbour in Ross House and, although we will miss her, we know that this move is a good prospect for Lin. I would like to wish Lin all the best for the future and to thank her for her continued assistance in training Kristen to take over her role. OWLS Most of you would be aware that Owl Badges are sold by state Retina Australia groups throughout Australia. Owls were chosen as a symbol for retinal disease because they have acute vision and can see particularly well at night, which is an opportunity denied many people with retinal disease who often see blurred images and suffer from night blindness or tunnel vision. Normally we have a different Owl Badge for sale each year and for 2011, this badge features the Boobook Owl. The Boobook is the smallest of the Australian owls and is brown with white spots. It is a nocturnal hunter and renowned for its ability to swoop upon unsuspecting prey in the darkness. If you would like to add the Boobook Owl to your collection, please contact the office. Each Badge costs $2 and as well as the Boobooks, we still have a number of Owl Badges from previous years for sale. Currently we are also selling Soft Beany Owls and Hand Puppet Snow Owls. The Soft Beany Owl is very soft and furry and stands 15cm high and approximately 15cm around its widest part. It retails for $10 and is suitable for small children. The Hand Puppet Snow Owl is 25 cm in height and being a puppet, a small-medium adult hand can fit inside the Owl with thumb and small finger in the "hands" and the other three fingers in the "head". It is also very soft and fluffy and will retail for $15. Please do not hesitate to phone Kristen in the office if you are interested in purchasing any of the Owls. ENTERTAINMENT BOOKS The Entertainment Books which contain vouchers for discounts at restaurants, arts, attractions, hotel accommodation and much more, will soon become available for purchase from the Office. These Books sell for $65, and for each one sold, Retina Australia Vic receives $13. Members are able to pre order now so that as soon as the books become available they can be dispatched to you. The good thing about obtaining books early is that vouchers can be used immediately and will not expire until 1st June 2012. NATIONAL DISABILITY INSURANCE SCHEME FORUM The National Disability Insurance Scheme has been flagged as a scheme which could be one of the most significant reforms in our lifetime. The Australian Government has asked the Productivity Commission to look at a new system to improve long term care and support services for people with disability and their carers and families. This Scheme would provide insurance cover for all Australians in the event of a significant disability including loss of vision and blindness. Blind Citizens Australia will be making a submission to this review at the end of April and would like to include feedback received from our members. You are welcome to attend one of their forums to learn more about the proposed scheme and give your feedback. Please contact BCA on 1800 033 660 for further details. End of article Beginning of article Message from NZ Below is a message for the entire Retina International community from our NZ counterparts in the aftermath of the Christchurch earthquake: Greetings everyone, I’m sure many of you have now heard of the devastation and tragedy resulting from an earthquake on February 22nd in Christchurch, New Zealand that has resulted in a large number of lives lost and injuries sustained. While we can’t be completely sure of the effects of the earthquake on all of our retina New Zealand family living in the area, initial reports from our executive member in Christchurch, Petronella Spicer, have not included any news of injuries or deaths so we are optimistic that our nearest and dearest have escaped the worst possible outcomes of this tragic natural disaster. As the images and audio reports will no doubt make it clear, damage to infrastructure leading to all manner of distressful situations, will take time to overcome. The people of Christchurch, however, are well-known for their pride in their city, their resilience and community spirit and their determination to succeed. We have no doubt this will mean the city will recover and rebuild quickly and realise the unique opportunity they now have to create a cityscape that is innovative, unique and robust. We know many of you, being the kind of selfless humanitarian people you are, will be sending your best wishes and tangible support to the people of Christchurch, and we thank you deeply for your support. With best wishes, Fraser Alexander and the Retina New Zealand Executive End of Article Beginning of Article Tax Rebates for Adaptive Technology Every student with or without a disability may be eligible for a rebate by the Australian Tax Office under the "education tax rebate". See the conditions on the ATO website link to the "Education Tax Refund" www.educationtaxrefund.gov.au/what-can-i-claim.html The ATO has also advised that the cost of some equipment designed for people who are vision impaired is now eligible for the medical expenses rebate. The rebate means that 20% of all eligible expenses above $1,250 can be claimed. Approved products include a talking computer, reading system and CCTVs, provided they have been prescribed by a medical doctor, optician or optometrist. Consult your tax pack for details. Source: Blind Citizens Australia Parent News, Jan/Feb 2011. End of Article Beginning of Article FEATURES Victorian Blind Cricket Moves Forward Over the past five years, the game of Blind Cricket has experienced something of a decline in numbers, and the Victorian Blind Cricket Association (VBCA) went from a six team competition to a four team competition due in part to the retirement of ageing players, and the introduction of other Vision Impaired sports. Privacy laws, and the integration of vision impaired students into public and private schools, means that we have experienced difficulties being able to find and access those eligible to play our game. Since the introduction of a dedicated player recruitment position to our Board and a major upgrade to our website http://www.vbca.org.au we are beginning to turn things around. Blind Cricket is open to anybody who wants to play the game. The game of blind cricket is not too different from the sighted game, with a couple of exceptions such as the ball and the fact that it is bowled underarm, mainly for safety reasons, and the fact that in our game byes can’t be taken if the ball passes the wicket keeper. Blind Cricket in Australia is played on three levels, Local, National and International, which means that players can enjoy a strong domestic competition, at whatever skill level they possess. You don’t have to be a champion to play grass roots blind cricket. However, a player who has strong skills may aspire to play at national level. We have National Championships every second year in December-January, this year, to be played in Brisbane, and anybody who makes a national championships squad, and aspires to, can try out to play for Australia in World Cup, Ashes, or other international fixtures both at home and abroad. Over the past two years or so, we have created a player development session on Saturday mornings at our grounds behind Vision Australia, 454 Glenferrie Road Kooyong. Players young or old, and anybody interested in checking out our game will be coached, and when ready, allocated to a team enabling them to commence their domestic career. We aim to establish new teams in the near future which will both strengthen our domestic season, and allow more people to become actively involved. We also like to involve parents, partners and friends of our participants to become involved as scorers, umpires or volunteers to assist with off field activities such as our canteen, ground maintenance fundraising or any other task which needs to be undertaken. These roles are all voluntary and we appreciate the time and effort of those who assist. As mentioned earlier, the only prerequisite to become a blind cricketer is to qualify for the Centrelink Disability Support Blind Pension. Your ophthalmologist will be able to advise on this. You don’t have to receive this payment as this would preclude underage players, and our philosophy is that any player of any age, race or gender is welcome. If readers are keen to find out more about our great game, please visit our website, and click on the contact us link, or call Alf O’Neill on 0411 705 111. Supplied by Alf O’Neill, President, V.B.C.A. End of article Beginning of Article Blind Driver on Raceway For the first time a blind individual has driven a street vehicle in public without the assistance of a sighted person. Mark Anthony Riccobono, a blind executive who directs technology, research, and education programs for The National Federation of the Blind in the US, was behind the wheel of a Ford Escape hybrid equipped with non-visual technology and successfully navigated 1.5 miles of the road course section of the famed track at the Daytona International Speedway in Florida. The historic demonstration was part of pre-race activities leading up to the Rolex 24. Mr. Riccobono not only successfully navigated the several turns of the road course but also avoided obstacles, some of which were stationary and some of which were thrown into his path at random from a van driving in front of him. Later he successfully passed the van without collision. The Ford Escape was equipped with laser range-finding censors that conveyed information to a computer inside the vehicle, allowing it to create and constantly update a three-dimensional map of the road environment. The computer sent directions to vibrating gloves on the driver's hands, indicating which way to steer, and to a vibrating strip on which he was seated, indicating when to speed up, slow down, or stop. Source: The National Federation of the Blind, Press Release, January 29, 2011. End of Article Beginning of Article What are Orphan Drugs? The Research Update in this edition focuses considerably on developments in orphan drug designations. But what exactly are orphan drugs? An orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease. The assignment of orphan status to a disease and to any drugs developed to treat it is a matter of public policy in many countries, and has resulted in medical breakthroughs that may not have otherwise been achieved due to the economics of drug research and development. The Orphan Drug Act (ODA) of January 1983, passed in the US, with lobbying from the National Organisation for Rare Disorders, is meant to encourage pharmaceutical companies to develop drugs for diseases that have a small market. Under the law, companies that develop such a drug may sell it without competition for seven years, and may get clinical trial tax incentives. The European Union (EU) has enacted similar legislation in which pharmaceuticals developed to treat rare diseases are referred to as "orphan medicinal products." Orphan drug legislation also exists in Australia. The Australian orphan drugs program was set up in 1997. The program aims to ensure the availability of a greater range of treatments for rare diseases and allows the Therapeutic Goods Administration (TGA) to use information from the US Food and Drug Administration (FDA) Orphan Drugs Program as part of the Australian evaluation process. Source: Wikipedia and www.findlaw.com.au End of Article Beginning of Article F U N D I N G B O O S T The Foundation Fighting Blindness (FFB) has announced that Gordon and Lulie Gund and an anonymous donor have pledged $100 million over the next five years to support a variety of clinical, translational, and basic research projects. This represents an $80 million increase and three-year extension of their earlier $50 million joint pledge made in 2008. Another anonymous donor is committing at least $5 million for clinical research over the same time frame. End of Article Beginning of article RESEARCH UPDATE Recent Developments in Retinal Degeneration: There have been considerable advances in our knowledge of the pathogenesis of inherited retinal degenerations over the last five years that have lead to the development of some very promising treatments. Below, we have summarized some of our own findings examining new animal models of inherited retinal degeneration, ways to slow photoreceptor death and also novel ways of replacing lost photoreceptors. i) New animal models: Most research into the mechanisms of photoreceptor death have utilized animal models that carry mutations in rod associated proteins (e.g. rhodopsin). Whilst this work has been very important, it has little relevance to some of the rarer forms of retinal degeneration such as Leber Congenital Amaurosis. Recently, we have identified a novel mouse that replicates many of the features of one form of Leber Congenital Amaurosis. This mouse, called the Histidine Decarboxylase Null Mouse, develops severe changes in the outer retina because the support cells of the retina lack proteins that maintain the correct position of the rods and cones. These mice will be used by us now to study some of the rarer forms of retinal degeneration. ii) Slowing photoreceptor death: Much of our work over the last few years has been directed at examining whether dying rods release a toxic factor that affects neighbouring photoreceptors. Our work has shown that the energy molecule, ATP, is released in large amounts from dying rods and accelerates the death of neighbouring cells. We have tested two drugs known to block the action of ATP, and shown them to slow photoreceptor death in a mouse model of retinal degeneration. In addition, we have found that the rate of photoreceptor death is slowed in transgenic mice that lack the expression of the receptor to ATP. Agents that block the action of ATP are under development by large pharmaceutical companies because of their potential role in controlling some forms of pain. We hope our work expands the possible uses of these compounds into the ophthalmic area. iii) Novel ways of replacing lost photoreceptors: The two most exciting developments to restore vision in those who have few photoreceptors remaining are the development of electronic implants, and the use of gene therapy to target visual pigments to the remaining neurons of the inner retina. There are currently two large groups in Australia developing electronic implants to restore vision. One group is designing retinal implants: a wide-field device that sits underneath the retina, and another high visual acuity device that is designed to target the output neurons of the retina. It is hoped that trials for the wide view device in patients will begin in the next year. The high visual acuity device is currently undergoing preclinical testing. A second group, based at Monash University, is designing an implant to be inserted into the visual area of the brain. This device is intended to restore vision in those who have no remaining ganglion cells or an intact optic nerve. Currently this device is undergoing extensive preclinical development. Gene therapy has been used to target visual pigment to inner retinal neurons. The inner retina of those with inherited retinal degeneration is usually intact. By using gene therapy, inner retinal neurons can become light sensitive, performing the duties of photoreceptors. These studies are very exciting because the technology can be used in most patients with inherited retinal degeneration irrespective of the specific genetic cause of the disease. In summary, over the last few years our knowledge of inherited retinal degeneration has increased dramatically, to the point where treatments are now being tested in patients, with exciting results. Source: This article has been provided exclusively for The Achiever by Prof Erica Fletcher and Dr Ursula Greferath from the University of Melbourne. Dr Erica Fletcher is a recipient of Retina Australia research grant funds. Her research is aimed at examining in detail how the molecule, ATP, causes photoreceptor death, and whether blockade of this class of molecule slows photoreceptor death. Understanding how photoreceptors die is crucial for the development of therapeutic agents that slow the progression of RP. End of article Beginning of Article Retina International Celebrates Rare Disease Day: Monday, February 28, 2011 Orphan Drug Designations enable further development of Therapies for Rare Retinal Diseases For over thirty years patient led research groups have formed partnerships with leading researchers across the globe and together they have blazed a trail in the development of treatments and cures for rare retinal diseases such as Retinitits Pigmentosa, Usher Syndrome, Stargardts Disease, Macular Degeneration and Lebers Congenital Amaurosis (LCA), among others. Over the years these groups have raised significant funds to support world leading research and advocated at the highest level for national and international support of their efforts. In this time patients and researchers have become true partners and in so doing expedited the search for cures and treatments. Patient groups are now working closely with industry to ensure that the work they have supported can be facilitated through clinical trial development and the regulatory process to ensure treatments are available to those losing their sight as soon as possible. And the results of this intense work are now coming to fruition. With new orphan drug designations granted for treatments with the potential to cure and to treat rare forms of rare retinal degenerations over the last few months, on Rare Disease Day 2011 Retina International is delighted to highlight their progress. 1. On February 10th 2011 QLT-09100 Retinoid in LCA – received Orphan Drug Designation from the FDA. Dr. Rob Koenekoop of McGill University, Montreal, Canada has led the study on Leber congenital amaurosis (LCA) which causes blindness in children. 2. On December 17 a team led by Prof. Pete Humphries, Prof. Jane Farrer and Dr. Paul Kenna based at Trinity College Dublin in Ireland received Orphan Drug Designation for gene therapy to treat Rhodopsin linked RP. 3. On 23 March 2010, orphan designation (EU/3/10/727) was granted by the European Commission to Oxford BioMedica (UK) Ltd, United Kingdom, for lentiviral vector containing the human MYO7A gene for the treatment of retinitis pigmentosa in Usher syndrome. These are just three examples of recent designations in the area of rare retinal diseases. These orphan designations join Neurotech’s Encapsulated Cell Therapy which is now in stage 2 / 3 clinical trials. Along with orphan designations for therapies relating to the RPE65 gene, the opportunity for treatment is closer than ever. But what is an Orphan Drug Designation and why is it so important to all in the rare disease community? Pharmaceutical and biotechnology companies research and develop new medications to treat medical conditions but people who have rare diseases have not always had as much attention from researchers. This is because numbers are small and therefore the potential market for new drugs to treat them is not economically attractive. A rare disease is considered as one which occurs in less than 200,000 individuals in the United States, less than 5 per 10,000 individuals in the European Union, or less than 2000 individuals in Australia. Government regulatory agencies in the United States and the European Union have taken steps to change this reality. The Food and Drug Administration (FDA) which is responsible for ensuring the safety and efficacy of medications on the market in the United States established the Office of Orphan Product Development (OOPD) to facilitate the development of orphan drugs including offering research grants. Then in 1983 the Orphan Drug Act was passed in the United States. This for the first time offered incentives to induce companies to develop medical products for individuals with rare disorders. In 1995 The European Medicines Agency (EMA) which is responsible for ensuring the safety and efficacy of medications on the market in the European Union (EU) established the Committee on Orphan Medicinal Products (COMP), which oversees the development of orphan drugs in the EU. Like the US Congress, the EU government recognised the need to increase research and development of orphan drugs. An Orphan Drug Designation is not easy to achieve so it is very exciting for patients who have supported research into rare retinal degenerative disease to see so many orphan drug designations being applied to potential treatments. Every year brings us a step forward to a cure or treatment for retinal degenerations and we hope that the successes of the past year can be built upon and treatments will become a reality in the shortest possible time frame. Source: Retina International End of Article Beginning of Article Prevention of autosomal dominant retinitis pigmentosa by systemic drug therapy targeting heat shock protein 90 (Hsp90) Below is an abstract relating to a research project undertaken at The Ocular Genetics Unit, Department of Genetics, Trinity College, Dublin, Ireland, by Tam LC, Kiang AS, Campbell M, Keaney J, Farrar GJ, Humphries MM, Kenna PF and Humphries P. Retinitis pigmentosa (RP) is the most prevalent cause of registered visual handicap among working aged populations of developed countries. Up to 40% of autosomal dominant cases of disease are caused by mutations within the rhodopsin, RDS-peripherin and inosine 5'-monophosphate dehydrogenase type 1 (IMPDH1) genes, at least 30 mutations within which give rise to proteins that cause disease pathology by misfolding and aggregation. Given the genetic complexity of this disease, therapies that simultaneously target multiple mutations are of substantial logistic and economic significance. We show here, in a murine model of autosomal dominant RP (RP10) involving expression of an Arg224Pro mutation within the IMPDH1 gene, that treatment with the low-molecular-weight drug, 17-allylamino-17-demethoxygeldanamycin (17-AAG), an ansamycin antibiotic that binds to heat shock protein Hsp90, activating a heat shock response in mammalian cells, protects photoreceptors against degeneration induced by aggregating mutant IMPDH1 protein, systemic delivery of this low-molecular-weight drug to the retina being facilitated by RNA interference-mediated modulation of the inner-blood retina barrier. 17-AAG has an orphan drug status and is in current clinical use for the treatment of non-ocular diseases. These data show that a single low-molecular-weight drug has the potential to suppress a wide range of mutant proteins causing RP. Source: Hum Mol Genet. 2010 Nov 15;19(22):4421-36. End of article Beginning of article Orphan Drug Designation for RP Treatment A Canadian based biotechnology company, has announced that its oral synthetic retinoid product for the treatment of retinitis pigmentosa has been granted orphan drug designation. The drug had previously obtained orphan drug designation from the FDA for the treatment of Leber's Congenital Amaurosis (LCA). The oral synthetic retinoid, QLT091001, is a synthetic retinoid replacement for 11-cis-retinal which plays a key role in visual biochemistry. The rational for employing synthetic retinoids as a replacement therapy for deficiency of 11-cis-retinal is founded, in part, on the work of Prof. Krzysztof Palczewski, now based at the Department of Pharmacology, Case Western Reserve University. Pre-clinical studies conducted in mouse and dog models of LCA demonstrated a correction of the defect in rod photoreceptors in addition to restoring ERG responses to light. The compound completed a Phase 1a study in healthy volunteers and a Phase 1b study (in subjects at least 5 years of age) is currently underway. Commenting on the announcement Bob Butchofsky, President and Chief Executive Officer of the biotechnology company, QLT, stated that "we are excited to gain this second orphan drug designation status from the FDA for QLT091001, as it strengthens the synthetic retinoid program and allows for important advantages in the continued development path," said. We are hopeful these benefits will help us reach our goal of treating the thousands of patients suffering from these rare and sight debilitating inherited retinal diseases." QLT Inc. (QLTI), located in Vancouver and quoted on the NASDAQ GS with a value of $420M (14/1/11) was originally founded in the early 1980s to commercialise discoveries made at the University of British Columbia. Since then the company has expanded beyond its initial interests in immunology and diagnostics into the fields of cancer, drug delivery and retinopathy. Source: Uretina, Temple House, Dublin. End of Article Beginning of Article BOOBOOK OWL BADGE NOW AVAILABLE $2.00 each Buy for yourself or take a box of 50 for sale in your local optometrist etc. Contact Kristen for orders End of Article Beginning of Article Promising Cone Preserving Treatment: A promising treatment aimed at preserving cones, the retinal cells that provide central and daytime vision, is poised to move into a Phase I clinical trial within the next year. Known as rod-derived cone viability factor (RdCVF), the therapeutic protein has consistently preserved vision in several preclinical studies. RdCVF has received an orphan medicinal product designation from the European Commission, a regulatory agency similar to the FDA in the U.S. The orphan designation provides marketing, financial, and clinical research benefits to Fovea Pharmaceuticals, the French company developing the treatment. In 2005, Drs. José-Alain Sahel and Thierry Léveillard received the Foundation Fighting Blindness Annual Trustee Award for their discovery of RdCVF as a potential vision-saving treatment. The Foundation-funded French research team screened 210,000 genes to find a rod-derived protein that would protect cones. A majority of retinal degenerative diseases, including retinitis pigmentosa (RP), are caused by mutations in genes that affect rod cells. As a result, rods are the first photoreceptors to degenerate. Rods provide peripheral eyesight and vision in dark settings. However, once rods are gone, cones subsequently degenerate. This phenomenon led researchers to suspect that rods were secreting a factor (or multiple factors) that helped to preserve cones. Initially, the France-based clinical trial will involve monthly ocular injections of RdCVF into people with RP. The investigators are also evaluating gene therapy as a delivery mechanism to provide long-term, sustained release of RdCVF. One gene therapy treatment will likely be effective for several years. While the researchers will initially evaluate RdCVF in people with RP, they believe the treatment may preserve vision in people with a wide range of retinal degenerative diseases. Dr. Sahel notes that by keeping as few as 5 percent of cones alive, a person can continue to function independently. Drs. Sahel and Léveillard are co-founders of Fovea Pharmaceuticals. Dr. Sahel is centre director for the Foundation’s Paris Research Centre for the Study of Retinal Degenerative Diseases. Source: www.blindness.org End of Article Beginning of Article Understanding Stem Cell Therapy – Part Three Part Two in this series published in the last edition reviewed the early developments of stem cell research. In this final part we continue on with the more recent stem cell research developments. 2006 Scientists from Moran Eye Center and Advanced Cell Technology (ACT) reported that cells grown from human embryonic stem cells safely slowed vision loss when injected into the eyes of rats with a disease similar to macular degeneration. 2007 Researchers at the Institute of Regenerative Medicine discovered yet another potential source of embryonic stem cells in the amniotic fluid of the womb. 2007 ACT developed a harmless technique for removing a blastomere from an eight-cell human embryo (blastocyst). A blastomere is a cell resulting from the first few divisions of the ovum (egg) after fertilization. ACT announced successful production of a human embryonic stem cell line (hESC) using that method. 2007 A cooperative 5-year project was launched in the UK called the London Project to Cure Blindness. Its main intent is to develop stem cell therapy for AMD hopefully by the year 2012. 2007 Although doctors at Moorfields had some success with human subjects using adult stem cells from the patients’ own eyes, embryonic cells had been shown by the Sheffield scientists to be more malleable and easier to transplant than adult stem cells. 2008 Moorfields scientists are studying the potential transformation of Muller neuroglial cells from the patient’s own eyes. These would be removed from the eye, injected with a triggering chemical, grown in vitro (ie. in a petri dish) and transplanted back into the eye as stem cells. 2007 Two research groups described a method of creating induced pluripotent stem cells by inserting master regulator genes into the chromosomes of human skin cells. These altered cells appeared to behave like embryonic stem cells, which scientists hoped could eventually eliminate the need for using human embryos for research. 2009 Scientists at the University of Winconsin-Madison reported that they had reprogrammed skin cells and turned them into different kinds of retinal cells. This added to the evidence that stem cells made by reprogramming have similar, if not the same, abilities as embryonic stem cells. The University of Wisconsin scientists had not proved that retinal cells made in a dish can perform all of the functions of those made in the body. However, at least scientists now can take a skin biopsy from someone with a vision ailment, create retinal cells in a dish, and observe how the disease unfolds and how the cells die over time. Actual stem cell replacement in human retinas is still a little further away. It has been a fast decade since researchers first noticed the potential of stem cell transplantation as a retinal treatment. And the race continues full speed, as teams of scientists whittle away at the anatomical, monetary and ethical problems in the rush to make stem cell therapy a reality. End of Article Beginning of Article Plastic Artificial Retina is a Hit with Nerve Cells: “Creating neuro-prosthetic devices such as retinal implants is tricky because biological tissue doesn’t mix well with electronics. Metals and inorganic semiconductor materials can adversely affect the health or function of nerve cells”, says Fabio Benfenati at the Italian Institute of Technology in Milan. And over time the body’s natural defences can be incredibly hostile and corrosive to such materials. The emergence of flexible, organic semiconductor materials now offers an alternative. To test them, Benfenati and colleagues seeded nerve cells onto the surface of a light-sensitive semiconducting polymer similar to those used in some solar cells. The cells grew into extensive networks containing thousands of neurons. “We have proved that the materials are highly biocompatible,” says Benfenati. What’s more, the presence of the cells did not interfere with the optical properties of the polymer. The team were able to use the neuron-coated polymer as an electrode in a light-driven electrolytic cell. Artificial Colour Vision “When short pulses of light were aimed at specific sections of the polymer, only local neurons fired, suggesting the materials has the spatial selectivity needed for artificial retinas,” says Benfenati. “It’s very elegant science,” says Robert Greenberg, whose company Second Sight is close to receiving clinical approval for its retinal prosthesis. But Greenberg questions whether the electrical currents generated would be sufficient to stimulate nerve cells in the eye. “It’s still too early to tell,” says Benfenati. But he thinks the new material is worth further study, because of another benefit. “It can be tuned to respond only to specific wavelengths of light, raising the prospect of creating artificial colour vision,” he says. Source: Duncan Graham-Rowe, New Scientist, 26 January 2011. End of Article Beginning of Article Bone Marrow Stem Cell Study Below is an abstract of Phase I of this trial conducted in Brazil. Based on these results, the team has been given the green light to proceed to phase II with 20 patients, which is to begin this month. Purpose To evaluate the short-term (10 months) safety of a single intravitreal injection of autologous bone marrow-derived mononuclear cells in patients with retinitis pigmentosa or cone-rod dystrophy. Methods A prospective, Phase I, nonrandomized, open-label study including 3 patients with retinitis pigmentosa and 2 patients with cone-rod dystrophy, and an Early Treatment Diabetic Retinopathy Study best-corrected visual acuity of 20/200 or worse. Evaluations including best-corrected visual acuity, full-field electroretinography, kinetic visual field (Goldman), fluorescein and indocyanine green angiography, and optical coherence tomography were performed at baseline and 1, 7, 13, 18, 22, and 40 weeks after intravitreal injection of 10 x 106 autologous bone marrow-derived mononuclear cells (0.1 mL) into 1 study eye of each patient. Results No adverse event associated with the injection was observed. A 1-line improvement in best-corrected visual acuity was measured in 4 patients 1 week after injection and was maintained throughout follow-up. Three patients showed undetectable electroretinography responses at all study visits, while 1 patient demonstrated residual responses for dark-adapted standard flash stimulus (a wave amplitude approximately 35 [mu]V), which remained recordable throughout follow-up, and 1 patient showed a small response (a wave amplitude approximately 20 [mu]V) recordable only at Weeks 7, 13, 22, and 40. Visual fields showed no reduction (with a Goldman Standard V5e stimulus) for any patient at any visit. No other changes were observed on optical coherence tomography or fluorescein and indocyanine green angiograms. Conclusion Intravitreal injection of autologous bone marrow-derived mononuclear cells in eyes with advanced retinitis pigmentosa or cone-rod dystrophy was associated with no detectable structural or functional toxicity over a period of 10 months. Further studies are required to investigate the role, if any, of autologous bone marrow-derived mononuclear cell therapy in the management of retinal dystrophies. Source: Retina: The Journal of Retinal Vitreous Diseases, The Ophthalmic Communications Society Inc. End of Article Beginning of Article Systematic Approach to Stem Cell Treatment: Research has demonstrated the capacity for systemically injected stem cells to preserve photoreceptors, maintain visual function and rescue vascular pathology. The exciting developments show that a simple systemic injection of mesenchymal stem cells (MSCs) may soon find clinical application across a range of retinal pathologies including, age-related macular degeneration (AMD), retinitis pigmentosa (RP) and diabetic retinopathy (DR). MSCs are multipotent stem cells that can differentiate into a variety of cell types, including bone cells, cartilage cells and fat cells. The achievements represent a significant milestone in the potential treatment of several retinal disorders and additionally present a strategy to develop a "one-size-fits-all" approach through the targeting of common characteristics found among many retinal diseases. The statistics on several retinal degenerative disorders, coupled with a lack of effective treatments, underscore the significant clinical demand for new therapeutic options. In the US alone, AMD affects 10 million people over the age of 65 and 100,000 individuals are reported to suffer from RP. There are an additional 40,000 diabetic patients suffering from ocular complications every year, and retinopathy of prematurity is a significant challenge in premature infants. Beyond these relatively common ocular disorders there is a broad spectrum of retinal pathologies for which little or no treatment options are available. While each of the common disorders have a distinct molecular pathogenesis and genetic etiology, they equally demonstrate a number of common features including cone and rod photoreceptor cell death, altered vascular biology, diminished neuro-protectiveness, and difficulty of delivering potential therapeutics to the diseased tissues. A key theme of the research from the laboratory of Professor Ray Lund from Casey Eye Institute, Oregon Health & Science University in the US, is to develop a treatment strategy that might address these common features of retinal disease and thereby provide a clinical opportunity to tackle several retinopathies at once. In pursuit of such a goal Prof. Lund and colleagues have proposed that a cell-based therapy may provide the optimal clinical approach to targeting a number of photoreceptor degenerative diseases. In particular, a cell-based therapy capable of providing generic neuro- and vascular-protective effects across the whole retina is proposed to represent the ideal approach and, following several years study by the Oregon research team, the systemic application of mesenchymal stem cells (MSCs) is thought to provide just such an optimal therapeutic strategy. Source: EURETINA, Temple House, Temple Road, Blackrock, Co Dublin. End of Article Beginning of article Question Time with Helen Furmanczyk In this edition, Helen Furmanczyk has kindly agreed to volunteer for Question Time. 1. What’s your earliest memory? My earliest memory is when I was 3 years old. We had gone to visit some family friends in Frankston. We ended up staying for 2 weeks and I would refuse to go to sleep at night unless I was with my mum. Sure enough I would go to sleep in my mum’s and dad’s bed and wake up in our friends six months’ cot. I was devastated in the morning, because I thought that I was too big to sleep in a baby’s cot. 2. What’s your idea of a good time? Good movie, good music, good wine, good food and travelling. 3. What’s your ideal holiday destination? Borneo and hopefully get to go to Nepal. 4. Who inspires you? People with disabilities who achieve their goals in life. 5. What makes you angry? People who do not think about their actions. 6. What’s the hardest thing you’ve ever done? Tell my parents that I had RP. 7. What’s the best thing you’ve ever done? Travelled to Greece on my own for about a year, when I was 21. 8. What do you like about Retina Australia (Vic)? Everything! 9. If you could change one thing about the world, what would it be? I would rid the world of the hatred it harbours and inject in its veins, understanding and kindness. 10. What’s the most important thing you’ve learnt about life? Life is the best teacher and you never stop learning. End of article Beginning of Article LAST WORD As soon as you trust yourself, you will know how to live. JOHANN WOLFGANG VON GOETHE, 1749-1832 The only thing we have to fear is fear itself. FRANKLIN DELANO ROOSEVELT, 1882-1945 End of Article Beginning of Article CHANGE OF ADDRESS OR OTHER DETAILS To advise change of address or name, please enter your new particulars below. Then mail the whole of this page, which includes your existing particulars, to: Retina Australia (Vic) Inc., 247–251 Flinders Lane, MELBOURNE VIC 3000, Fax to 03 9639 0979 or email to support@retinavic.org.au Name. New Postal Address. Telephone/s. New Email. End of Article Beginning of Article DISCLAIMER: Views expressed in this publication are not necessarily those of Retina Australia (Vic) Inc. Retina Australia (Vic) Inc accepts no responsibility and disclaims all liability for such views as well as for any information contained in articles and summaries of research reports, including but not restricted to, the use of pharmaceuticals or other products, items of equipment or practices. Retina Australia (Vic) Inc strongly suggests that persons seek advice from their medical practitioners before adopting any changed procedures, practices or products. End of Article