E-News August 2017

 

NEW LOOK FOR RETINA SOUTH AFRICA

We hope you like the new logo. This, together with our new website, brings our corporate image bang up-to-date. All the latest information on retinal conditions are on our website. We also feature stories of some of our members who are living exciting and successful lives despite having an Inherited Retinal Disorder [IRD]. Are you? If so, please send us your story to help inspire others. We thank Simplr Designsmiths who have done all the excellent designing on our website and branding and substantially sponsored the work. Website tips: the logo on the top left hand side is the home page button; to increase the font size use ctrl and + keys; to reduce ctrl and -, this works on all web pages.

WORLD RETINA WEEK 19 – 25 SEPTEMBER - Help the gene hunters

World Retina Week is observed internationally to create awareness about Inherited Retinal Disorders [IRD] and the progress towards a cure that research has made possible. Phenomenal international research findings in the fields of gene replacement, stem cell therapy, pharmaceutical interventions, Optogenetics and gene editing now offer hope for imminent treatment. To ensure that South Africans are included in this remarkable progress, Retina South Africa is mounting an extensive media campaign to create awareness of the progress towards therapy. If you have any media contacts please let us know. Thanks to the generous sponsorship of Bausch and Lomb posters and pamphlets will be distributed throughout South Africa.

HELP THE GENE HUNTERS

The gene hunters at the Division of Human Genetics at the University of Cape Town are our partners in the quest to find the gene mutations in South African families. We are asking Eye Care professionals to refer their IRD patients to us and patients are being encouraged to help the gene hunters by registering for a genetic test. Some funding is available for genetic tests for young people under the age of 25.

 

BREAKING NEWS

We are presently sending DNA overseas for sophisticated Next Generation Sequencing testing – at great cost and long delays. The National Research Foundation has now sponsored this cutting edge technology at the Division of Human Genetics at the University of Cape Town. In order to customize this machine to enable it to find IRD gene mutations, we need to fund a specialized Diagnostic panel. We thank the Dis- Chem Foundation for their generous donation of R100 000 towards the target of R900 000 we need for this exciting project. The panel will speed up the hunt, reduce costs and find the elusive gene mutations unique to our South African indigenous populations. Once established this panel will place us at the forefront of genetic research as it will be the only technology geared to find IRD genes on the African continent.

To support us, please donate R10 by texting ‘Dream’ to 38267. Tax deductions and BBEE points are available for large and corporate sponsors. To donate go to www.retinasa.org.za. We need your help to achieve this dream.

1st Ever gene therapy for IRD being registered

The American FDA has approved the priority review for commercial registration of LUXTURNA ( Voretigene Neparvovec) by Spark Therapeutics. This gene therapy is for RPE 65- mediated Inherited Retinal Dystrophy – Leber Congenital Amaurosis and early onset Retinitis Pigmentosa [RP]. Patients from 4- 44 years of age have benefited from this one-time therapy to replace the RPE65 gene. Registration is expected in January 2018 and an application to the European Medicines Agency is being submitted. Although this journey, from the 1st ever patient trial to registration application took ten long years, we are sure that the ground breaking work done by all the researchers and funders have paved the way to ensure that in future the journey will be smoother and swifter. The success of this research was made possible by funding from Fighting Blindness, USA, the American National Institute of Health and the dedicated and tireless work of many researchers such as Robin Ali and Jean Bennett. We salute them all.

  • Prof Robin Ali, Moorfields, London was team leader of the very first RPE65 gene therapy. He feels that the viral vector that is used to transfer the gene needs to be improved and has started a trial using a new viral vector that is 500x more effective. Seven patients have been treated with low and mid-dose treatments. A high dose arm is in progress and once this is complete the treatment will be extended to young patients. The trial will be extended to the Kellogg Centre in Michigan and 18 patients will be treated in total. Completion is expected in 12 months.

 

 

GENE EDITING- THE FUTURE OF GENETICS ?

CRISPR- Cas9 is a naturally occurring DNA editing process that bacteria use to disable viruses. It was only discovered five years ago by Elizabeth Doudna and colleagues but is now the subject of intense investigation by genetic researchers. It recently made headline news when American and Korean researchers used this precise gene editing process to successfully edit human embryos being fertilized by sperm containing a dominantly inherited gene mutation for a severe heart condition. The embryos exhibited very few unwanted genetic changes but a ban on gene editing in humans means that embryos edited with CRIPR –Cas 9 cannot be implanted.

Editas, a gene editing company is developing a CRISPR/Cas9 therapy for LCA 10 caused by a mutation in the CEP290 gene. The therapy works by “cutting out” the mutation so that expression of the gene returns to normal. Editas is working toward a clinical trial for the therapy. Other research in animal models is in progress with promising results.

The future use of this technology may extend far beyond editing genetic mutations and the DNA of cancer cells- re-engineering immune cells and modifying yeast to produce drugs are just two of the possible applications of CRISPR-Cas9 gene-editing technology, according to Professor Toni Cathomen, director of the Institute for Cell and Gene Therapy at the University of Freiburg, Germany.

 

GENE THERAPY UPDATE

Phase 1/2 Sanofi study for Stargardt disease – 24 patients have been treated at either Casey Eye Institute, Institut de la Vision, Bascom Palmer Eye Institute (University of Miami), University of Iowa, or Cullen Eye Institute (Baylor College of Medicine) and nine people have been treated in their Usher syndrome type 1B study at Casey and the Institut de la Vision.

Phase I/II clinical trial for Achromatopsia (CNGA3 mutations), an IRD causing day blindness, impaired colour vision and poor perception of detail, is in progress at the University Hospital Tuebingen in Germany. Nine people have been treated.

Choroideremia- Phase I/II gene therapy clinical trial at Scheie Eye Institute (University of Pennsylvania). Nine people have been treated.

X Linked RP (RPGR gene) is in progress in Oxford [Nightstar X trial].

Leber hereditary optic neuropathy (LHON affects mitochondria in cells of the inner retina ) Phase I trial at Bascom Palmer Eye Institute (University of Miami), six patients treated.

Choroideremia trial (also at Bascom Palmer). Six patients have been treated in the first year of the Phase II gene therapy trial and overall vision has been relatively stable.

LHON – Phase I/II Gene therapy trial at the University of Pittsburgh School of Medicine and Institut de la Vision (Paris). 21 Patients treated with some vision improvement.

Precision BioSciences is developing a genome-editing technology known as ARCUS, derived from a natural genome-editing enzyme called a homing endonuclease which recognizes, binds to, and cuts the mutated DNA. They are developing a therapy for autosomal dominant RP caused by the P23H mutation in the rhodopsin gene.

 

STEM CELL NEWS

iPSC derived from blood or skin cells for dry AMD, Helios KK and NIH.

RPE therapy for dry AMD derived from human retinal cells, Neural Stem Cell Institute.

Phase 1/2 RPE clinical trial for dry AMD using embryonic stem cells, Cell Cure Neuroscience.

Phase 1/2 clinical trial for wet AMD building RPE onto a scaffold at the University College London, in collaboration with the University of California, Santa Barbara.

Phase I/IIa clinical trial at Massachusetts Eye and Ear Infirmary using human retinal progenitor cells to restore vision for people with retinitis pigmentosa (RP). The ReNeuron trial has treated six patients with no serious adverse events.

Emerging iPSC-derived therapy to repair vasculature in retinal diseases such as diabetic retinopathy at the Indiana University School of Medicine.

PHARMACEUTICAL INTERVENTIONS

QLT Retinoid for LCA and RP – RPE65 gene now in clinical trial.

Researchers in Peking and Beijing have shown that melatonin could slow the rate of degeneration in a mouse model of RP.

Researchers in Jinan City, China have shown that Alpha Lipoic Acid treatment improves vision-related quality of life in patients with dry AMD probably by increasing antioxidant activity.

The FDA-approved cancer drug Sunitinib supports survival of photoreceptors and retinal ganglion cells, Johns Hopkins University, USA

OPTOGENETICS AND PHOTOSWITCHES-

This is the delivery of light sensitive molecules to the neural layer of the retina.

GenSight at the Institut de la Vision, is developing an optogenetic therapy which is designed to work safely and effectively in natural lighting conditions. The GenSight approach uses gene therapy to bestow light sensitivity to a retina that is no longer providing vision. They claim that their system is more advanced and optimized than many other emerging optogenetic options.

Researchers at the University of California, Berkeley, have published results of a study showing that “BENAQ” a “photo-switch” molecule may be capable of restoring vision in animal models of retinal degeneration. The study showed that BENAQ was capable of restoring retinal responses to white light of an intensity similar to ordinary daylight. A single intra-ocular injection of BENAQ appeared to photosensitize a blind retina for up to a month, re-establishing electrophysiological and behavioral responses with no signs of toxicity. Tests also demonstrated that BENAQ was non-toxic to mice and rabbits at concentrations 10-fold higher than the concentration required to trigger light-sensitivity.

INTERESTING FACTS

  • Australian researchers have studied the collective influence of physical activity, diet, smoking and alcohol consumption on the prevalence and    incidence of AMD. 2428 people participated in the 15 year study. Cross-     sectional analysis showed that participants who engaged in all 4 poor health behaviors versus those who did not engage in unhealthy behaviors had greater odds of developing AMD or the worsening of existing AMD.
  • Researchers in Atlanta, Georgia have found that Aerobic exercise is neuroprotective in animal models of retinal degeneration. A subsequent study looked at the relationship between physical activity levels in patients with RP and their vision-related quality-of-life (QOL). Their results showed increased physical activity is associated with greater self-reported visual function and QOL.
  • Doctors at the Eye Hospital in Oxford, UK, have highlighted the serious retinal damage caused by the prolonged use of hydroxychloroquine (HCQ). This drug is used to treat autoimmune conditions, rheumatoid arthritis and systemic lupus erythematosus (SLE). Please check with your health care provider.
  • A team at the University of Bern has demonstrated that the composition of the intestinal microbiome in patients with AMD, compared to controls, indicates an enrichment of certain microbial genera. The finding may open a significant field of research and therapeutic development. “Gut health” has been the subject of intensive study in the last few years and the links between the microbiome and dozens of diseases are being investigated.

DOCTORATE FOR LISA

Lisa Roberts, Senior Scientist in the Division of Human Genetics at the University of Cape Town (UCT), graduated with a Doctor of Philosophy (PhD) in Human Genetics on 14 July 2017. She says: “Although it was very challenging, trying to balance a part-time PhD with a full time job, overall the experience of doing a doctorate was very rewarding. It was hard work, and demanded a lot of discipline for the better part of three years. I couldn’t have done it if I hadn’t been interested in the research topic, or without the support from my family, friends and colleagues.”

A PhD candidate undertakes independent academic research and must submit a thesis (dissertation), contributing original knowledge on the topic. Lisa’s PhD thesis was entitled “Genetic analysis of inherited retinal diseases in indigenous southern African populations”.

Lisa’s research investigated the genes and mutations causing inherited blindness. She focused on indigenous southern African families, who are under-represented in global genomic research. She began her PhD journey in 2014, by reviewing the results of 30 years of genetic research into inherited retinal diseases (IRD) undertaken in the Division of Human Genetics at UCT. This review of the IRD DNA registry led to the identification of a single genetic mutation which is responsible for ~43% of the cases of Usher syndrome (the most common cause of deaf-blindness) in this population.

Lisa then went on to examine 16 families with inherited vision loss, who lacked a genetic diagnosis using older technology. She undertook a 3 month research visit to the Neurobiology, Neurodegeneration & Repair Laboratory (NNRL), in the National Eye Institute at the National Institutes of Health (NIH), in Bethesda, Maryland, USA. Lisa says: “This was an incredible learning experience that I am very grateful for”. There, under the guidance of her co-supervisor Dr Anand Swaroop and his team, they used the latest ‘next-generation sequencing’ technology, and performed Whole Exome Sequencing to capture and sequence the entire exome (which is the coding portion of the human genome and therefore most likely to carry disease-causing mutations). A vast amount of genomic data was generated, and her analysis moved from the laboratory to the computer, and back again, over the next few years.

Ultimately, Lisa reported in her thesis that she had identified the causative genetic mutation in ~73% of the families studied, and that 70% of the mutations identified have never been reported elsewhere. In addition, by collaborating with international researchers, a new retinal-disease gene (IDH3A), responsible for severe vision loss in one local family, was identified. (Announced previously at http://www.retinasa.org.za/new-gene-find-at-uct/).

Lisa’s PhD project resulted in three peer-reviewed publications in international specialist journals. Her results emphasised that African populations (who display vast genomic diversity) play an important role in gene discovery and in understanding the genetic contributions to disease. Her research generated new knowledge about inherited blindness in South Africa and will improve genetic diagnostic services for indigenous African families. These findings may be applicable to other African populations, and the IRD team at UCT hopes to extend its research into other countries on the continent.

Editors note: Lisa has been involved with our research projects for many years. She is totally dedicated and the progress that we have made in finding genetic mutations in so many South African families is due to her knowledge and skill. We congratulate her on this wonderful achievement

UBER ASSIST

UberAssist is now available in Johannesburg. This service has been designed to help senior and disabled riders who require additional assistance to get around the city more conveniently. This will assist people who have to order a larger car due to their wheel chair or wish to ensure their driver will pick them up if they have a guide dog. These drivers have completed some training in disability awareness. Uber ASSIST is priced at the same rates as Uber X Please see Link https://www.uber.com/en-ZA/blog/johannesburg/uberassist- making-johannesburg-accessible/

NATIONAL NEWS

 

AGM & NATIONAL MANAGEMENT COMMITTEE MEETING

These meetings were held on 4th and 5th August in Johannesburg. James Cape was re-elected as National Chairman, Mariza Jurgens as Vice- Chair, Jean Bowler as treasurer and Claudette Medefindt as Secretary. Manny Claudette Medefindt as Secretary. Manny Moodley was unavailable to stand for Vice – Chairman and was thanked for his service. The new interim constitution, unifying Retina SA as a single entity has now gone to the various branches for discussion. This is one step further towards unifying and empowering all our members.

FUND RAISING

You still have time to buy raffle tickets for the Mazda 2 raffle. Tickets are only R10 each and are available from our national office.

Thank you to all the members who have paid their annual membership fees. Your status as a member in good standing will be important going forward. A membership fee waiver is available for needy families, on application.

Don’t forget to SMS “Dream” to 38267 – R10 per SMS and encourage all your contacts to do the same. Thank you if you have nominated Retina South Africa as a beneficiary on My School/ My Planet at www.myschool.co.za and remember to swipe your card at all the participating outlets. As clinical trials approach we truly need all our members to participate. Please ask you employer to consider us as a recipient for a CSI donation. Donations exceeding R250 are eligible on request for a Section 18a tax deduction.

Please deposit membership fees plus any donations and fundraising contribution to: Retina South Africa, Standard Bank, Bedfordview branch, Code 018305, Account number 020312164. For overseas payments the swift code is SBZAZAJ; or go to the donate now page on this website.

REMEMBERING ANNE- MARIE

Anne- Marie Hicks died recently. She is fondly remembered for her kind and expert help and support to Retina South Africa over many years. Our condolences to Anton van Rooyen and family. RIP.

FREE APP

Often need a sighted friend who could help you identify an object? Be Specular is an international community of sighted volunteers that will assist visually impaired people by text. For more info:

www.bespecular.com

 

SPONSOR ACKNOWLEDGEMENT

BAUSCH AND LOMB

The production and distribution of this newsletter is sponsored by Bausch and Lomb via an unconditional educational grant to Retina South Africa. The views and comments expressed in the newsletter do not necessarily reflect the views of Bausch and Lomb.

THANK YOU BAUSCH AND LOMB FOR YOUR CONTINUED SUPPORT OF OUR WORK.

 

 

Read more news & insights in OUR BLOG section

Sign Up For Our E-Newsletter

To receive our E-Newsletter right to your inbox, please complete this form

Please leave this field empty.