PERSPECTIVE Communicating the Promise for Ocular Gene Therapies: Challenges and Recommendations SHELLY BENJAMINY, STEPHANIE P. KOWAL, IAN M. MACDONALD, AND TANIA BUBELA

 PURPOSE:

To identify challenges and pose solutions for communications about ocular gene therapy between patients and clinicians as clinical research progresses.  DESIGN: Literature review with recommendations.  METHODS: Literature review of science communication best practices to inform recommendations for patient-clinician discussions about ocular gene therapy.  RESULTS: Clinicians need to employ communications about ocular gene therapy that are both attentive to patient priorities and concerns and responsive to other sources of information, including overly positive news media and the Internet. Coverage often conflates research with therapy—clinical trials are experimental and are not risk free. If proven safe and efficacious, gene therapy may present a treatment but not a cure for patients who have already experienced vision loss. Clinicians can assist patients by providing realistic estimates for lengthy clinical development timelines and positioning current research within models of clinical translation. This enables patients to weigh future therapeutic options when making current disease management decisions.  CONCLUSIONS: Ocular gene therapy clinical trials are raising hopes for treating a myriad of hereditary retinopathies, but most such therapies are many years in the future. Clinicians should be prepared to counter overly positive messaging, found in news media and on the Internet, with optimism tempered by evidence to support the ethical translation of gene therapy and other novel biotherapeutics. (Am J Ophthalmol 2015;160(3):408–415. Ó 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).)

Accepted for publication May 26, 2015. From the School of Public Health (S.B., S.P.K., T.B.); and the Department of Ophthalmology and Visual Sciences, University of Alberta (I.M.M.), Edmonton, Alberta, Canada. S. Benjaminy is currently with the National Core for Neuroethics, Department of Medicine, University of British Columbia, Vancouver, BC, Canada. Inquiries to Tania Bubela, School of Public Health, 3-300 Edmonton Clinic Health Academy, 11405 – 87 Ave, Edmonton, AB, Canada T6G 1C9; e-mail: [email protected]

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2015

R

ECENT SUCCESSES IN OCULAR GENE THERAPY CLIN-

ical trials have revitalized hopes for a field that was previously marked by high-profile disappointments.1 Pioneering clinical trials to address mutations of the RPE65 gene that cause Leber congenital amaurosis (LCA) established safety and demonstrated improvements in visual function.2–4 These studies were celebrated by the research community and the media,5 igniting hopes for gene therapies for related retinopathies. Our goal here is to identify challenges and pose solutions for communications about ocular gene therapy between patients and clinicians as clinical research progresses. Although we focus on gene therapy, similar considerations apply to other experimental biotherapeutics. The discussion is timely. One research group at the University of Pennsylvania reports that positive safety and efficacy results from the LCA trials have been sustained over time in adults and children6; readministration in the second eye of 3 adult patients was both safe and efficacious after previous exposure to the vector.6 A fully enrolled phase III pediatric clinical trial is underway and expected to report in late 2015 (NCT00999609). The pediatric trial is crucial because LCA studies suggest a therapeutic window for visual gain, with earlier application leading to more dramatic responses.7 Although these results appear promising, studies in dogs suggest that degenerative processes may continue after the gene therapy intervention, if such degeneration has already commenced.8 In humans, a second research group reported that gene therapy improves vision for at least 3 years, but photoreceptor degeneration also continues at the same rate as in the natural course of the disease.9 Long-term follow-up (4.5-6 years) from 3 treated patients indicated progressive diminution of the areas of improved vision.10 Similar results were reported by a team from the United Kingdom: retinal sensitivity improved after gene therapy but diminished after 12 months.11 Gene therapy may therefore not offer a permanent treatment, and most benefit is likely if the intervention occurs prior to the onset of retinal degeneration.8 Some patients may require a second round of gene therapy, and gene therapy may best be used in combination with other medications, if and when these are developed.12 Research continues to improve gene therapy

THE AUTHORS. PUBLISHED

BY

ELSEVIER INC.

0002-9394 http://dx.doi.org/10.1016/j.ajo.2015.05.026

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TABLE. Completed or Active Ocular Gene Therapy Clinical Trials Registered in ClinicalTrials.gov by May 2015 and Associated PUBMED Publications Disease

Choroideremia

Leber congenital amaurosis

COMMUNICATING THE PROMISE FOR OCULAR GENE THERAPIES

Leber hereditary optic neuropathy

Neovascular age-related macular degeneration

Retinitis pigmentosa Retinoschisis Stargardt macular degeneration Usher syndrome

Intervention

Phase

Enrollment

Age Group

Start Year - End Year

Status

AAV2-hCHM rAAV2 REP1b rAAV2.REP1b rAAV2.REP1b AAV2-hRPE65v2 AAV2-hRPE65v2 AAV2-hRPE65v2 rAAV2-CB-hRPE65 rAAV 2/2.hRPE65p.hRPE65 rAAV2-CBSB-hRPE65 rAAV2/4.hRPE65 rAAV2-hRPE65 scAAV2-P1ND4v2 rAAV2-ND4

I/II II I/II I III I/II I I/II I/II I I/II I I N/A

10 30 12 6 24 12 12 12 12 15 9 10 27 6

A,S A,S A,S A,S C,A,S C,A,S C,A,S C,A,S C,A C,A,S C,A C,A,S A C,A

2015–2021 2015–2018 2011–2015 2015–2018 2012–2029 2010–2026 2007–2024 2008–2027 2007–N/A 2007–2026 2011–2014 2010–2017 2014–2019 2011–2013

R NYR R R ONR ONR ONR ONR ONR ONR Com R R R

rAAV.sFlt-1 AAV2-sFLT01 RetinoStat RetinoStat AdGVPEDF.11D rAAV2-VMD2-hMERTK

I/II I I I I I

40 34 21 21 N/A 6

A,S A,S A,S A,S A,S C,A,S

2011–2015 2010–2018 2011–2015 2012–2027 N/A 2011–2023

ONR ONR ONR R Com R

rAAV2tYF-CB-hRS1 AAV-RS1 StarGen StarGen UshStat UshStat

I/II I/II I/II I/II I/II I/II

27 100 46 28 18 18

C,A,S A,S C,A,S A,S A,S A,S

2015–2020 2014–2017 2011–2017 2012–2022 2012–2017 2013–2022

NYR R R R R R

Sponsor a

Spark Therapeutics University of Oxford University of Oxford University of Alberta Spark Therapeuticsa Spark Therapeuticsa Spark Therapeuticsa Applied Genetic Technologiesa University College, London University of Pennsylvania Nantes University Hospital Hadassah Medical Organization John Guy, University of Miami Bin Li, Huazhong University of Science and Technology Lions Eye Institute, Australia Genzyme, a Sanofi Coa Oxford BioMedicaa Oxford BioMedicaa GenVeca Fowzan Alkuraya, King Khaled Eye Specialist Hospital Applied Genetic Technologiesa National Eye Institute Sanofia Sanofia Sanofia Sanofia

Clinical Trial Identifier

NCT02341807 NCT02407678 NCT01461213c NCT02077361 NCT00999609 NCT01208389 NCT00516477d NCT00749957 NCT00643747e NCT00481546f NCT01496040 NCT00821340 NCT02161380 NCT01267422 NCT01494805 NCT01024998 NCT01301443 NCT01678872 NCT00109499 NCT01482195 NCT02416622 NCT02317887 NCT01367444 NCT01736592 NCT01505062g NCT02065011

A ¼ adult; C ¼ child; Com ¼ completed; N/A ¼ not available; NYR ¼ not yet open for participant recruitment; ONR ¼ ongoing, but not recruiting participants; R ¼ recruiting/enrolling by invitation; S ¼ senior. a Industry sponsor. b NightstaRx AAV2-REP1 product. c Results published by Seitz et al13 (PubMed ID 25744334) and MacLaren et al14 (PubMed ID: 24439297). d Results published by Melillo et al15 (PubMed ID: 22812667), Maguire et al7 (PubMed ID: 19854499), and Maguire et al4 (PubMed ID: 18441370). e Results published by Bainbridge et al11 (PubMed ID: 25938638) and Bainbridge et al2 (PubMed ID: 18441371). f Results published by Jacobson et al10 (PubMed ID: 25936984), Cideciyan et al16 (PubMed ID: 25537204), and Jacobson et al17 (PubMed ID: 21911650). g Results published by Zallocchi et al18 (PubMed ID: 24705452).

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vectors and surgical delivery to ensure that patients receive an optimal dose for long-lasting effects.12 The LCA trials have paved the way for other retinopathies (Table). Public and private investments now support companies created to advance clinical development of ocular gene therapy. Spark Therapeutics has licensed technologies from the Children’s Hospital of Philadelphia, including those designed for LCA and choroideremia (http://www.sparktx.com/). NightstaRx was similarly launched in the United Kingdom to develop a gene therapy product for choroideremia (http://www.nightstarx.com/). Spin-off companies such as these enable scale-up from clinical trials to gene therapies available to patients in the clinic. However, potential financial conflicts of interest for researchers conducting clinical trials and involved in sponsoring companies must be managed carefully. Clinical trial participants must be informed of any conflicts of interest during consent processes to ensure the integrity of the research. Lessons may be taken from the early days of gene therapy clinical trials. Financial conflicts of interest, along with improper informed consent and protocol violations, damaged the reputation and progress of the field following the death of Jesse Gelsinger in a gene therapy clinical trial at the University of Pennsylvania in 1999. Against this backdrop, patients and their families are increasingly likely to request information from clinicians about emerging therapies. Patients may ask about potential treatment options or about articles on experimental interventions that they have retrieved from external sources; patients may inquire about clinical trials and about the possibility of enrolling in such trials; and patients may ask about early or compassionate access programs that are available in some countries. These programs allow health care providers to apply for the use of investigational products such as unapproved drugs or devices that are still in clinical trial or market approval stages. To be eligible for such access programs, patients must have serious or lifethreatening conditions, have no alternative therapy options, and have no other product access option (including clinical trial participation), and the potential benefits of the product must outweigh the risks. This risk-vs-benefit ratio is difficult to characterize for products that are in early phases of clinical trials.

A COMMUNICATIONS LANDSCAPE OF PROMISE COMMUNICATIONS ABOUT CUTTING-EDGE RESEARCH

will not occur in an informational vacuum. When discussing research with patients, clinicians need to be attentive to patient priorities and concerns but also responsive to other sources of information. These sources include news media, patient advocacy organizations, industry, social media, health and research organization websites, and 410

other Internet sources, as well as family and friends. Forty percent of the American public follow health news stories closely,19 especially those that are personally relevant20; Internet access to health information is widespread and growing.21 Media coverage of genetic research, particularly clinical research, is highly positive, framed as a celebration of progress in research.22 News articles focus on benefits, while omitting or downplaying risks, and provide limited background information for readers to assess the validity or credibility of the research (including funding sources and potential conflicts of interest). They accelerate timelines by presenting preclinical or early-stage research as an imminent therapy or cure.23 News articles often contextualize research with a human-interest story focused on a hopeful patient or a heroic researcher.24 Media coverage of ocular gene therapy clearly follows this pattern.25 It describes a range of visual outcomes from slowing vision loss to a cure, even though the latter is clinically infeasible. This positive coverage of ocular gene therapy generates high expectations in patient communities. For example, after the highly publicized successes in early-phase LCA trials, clinical reports documented a trend of LCA patients and families wishing to access clinical trials.26 Less publicized was the caveat that the initial LCA trials addressed only 1 of 17 known genetic mutations underlying the disease, representing only 5% of LCA cases.26 Patient organizations, such as the Foundation Fighting Blindness (www.ffb.ca) and the Choroideremia Research Foundation (cureCHM.org), also contribute to the communications landscape. These organizations both fund innovative research and communicate with patients and the public about associated risks, benefits, and timelines. Featured prominently on these sites are current and planned gene therapy clinical trials. The Foundation Fighting Blindness provides up-to-date information on clinical trials and genetic testing resources and maintains a patient registry as a tool to connect individuals living with inherited eye diseases to scientists researching those conditions. The Choroideremia Research Foundation operates similarly, and has recently adopted the Foundation Fighting Blindness MyRetinaTracker (https://www. myretinatracker.org), a registry that allows patients to upload their genotypic, phenotypic, lifestyle, and other clinical data to enable de-identified research use. Such registries are facilitated by advancements in genetic testing, including next-generation sequencing, that enable molecular diagnostics.27,28 While access to genetic testing may be differentially covered by health care systems and insurance policies,29 if available, molecular diagnostics may improve health-related quality of life by providing valuable information for reproductive counseling in cases of de novo mutations, information necessary to enroll patients in clinical trials, and empowering patients with knowledge and the opportunity to actively drive the research process forward.30,31

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In summary, patients increasingly access health information from print and broadcast media sources and on the Internet and raise this information during clinical visits. However, it is challenging for patients to assess the accuracy and credibility of such information, and reports on research into ocular gene therapy and related biotherapeutics paint a highly optimistic view of timelines and expected outcomes. Studies consistently emphasize the relational nature of care (between patients and their families and clinicians) and demonstrate better outcomes if the concerns of patients are met.32 Here we discuss how clinicians might aid patients and families in navigating the complex web of information and supporting hope while keeping expectations grounded in current clinical and research realities.

CLINICAL COMMUNICATION TOPICS AND RECOMMENDATIONS  RESEARCH, NOT TREATMENT:

Coverage of novel biotherapeutics conflates research with therapy. The very use of the term ‘‘therapy’’ in a clinical research context implies demonstrated therapeutic effect,1 but cumulative evidence suggests that fewer than 1% of participants derive a direct benefit from phase I gene therapy clinical trials.33 Media articles use research and treatment terminology interchangeably,25 confusing research goals and the state of clinical development.34 This confusion is problematic in the context of clinical trial enrollment, as hope for therapeutic benefit from early-stage clinical trials exemplifies a ‘‘therapeutic misconception.’’35 Such a misconception may undermine consent processes in clinical trial enrollment, which require participants to understand the research goals.35 In reality, research extends along a developmental continuum from laboratory research using cell and animal models to preclinical or enabling research—the goals of which are to demonstrate safety and the proposed mode of action of the therapeutic for regulatory clinical trial applications—through the phases of clinical trials. Rates of attrition between phases of clinical trials are high. Of interventions that enter phase 1, only 15% receive market authorization from a regulatory agency following phase 3 clinical trials; the greatest attrition occurs in phase 236 and is likely worse for more complex biotherapeutics. Phase I clinical trials are designed to test safety and the maximum tolerable dose. Though some safety outcome measures blur with those for efficacy, small phase 1 studies are inadequately powered to test the latter. For example, the first clinical study on choroideremia gene transfer published in The Lancet reported on 6 patients.14 Similarly, published accounts of the LCA trials reported on 3 participants in the New England Journal of Medicine (2008), a dose-escalation study in 12 participants in The Lancet,7 VOL. 160, NO. 3

and a follow-up study 3 years after treatment in 5 participants.37 While preliminary results appear promising, these are not without the caveats discussed in the introduction. More definitive evidence of efficacy for LCA gene therapy will emerge from the phase III trial later this year; peerreviewed, published accounts demonstrating efficacy of ocular gene therapy remain, at present, limited. Recommendation. When discussing access to an investigational gene therapy product by way of a clinical trial or otherwise, clinicians should address sources of information, the goals of different phases of clinical trials, the credibility of the clinical trial (including the site, sponsor, and research team), and that clinical trials represent research, not therapy. Clinicians may point patients and families to credible sources of information. For example, the Foundation Fighting Blindness website, while acknowledging patient hopes for a treatment, explicitly states: ‘‘The word intervention is used instead of the word treatment to help people remember that the drug and/or surgery that the participant is receiving is not an established treatment. A clinical trial is not a treatment it is an experiment.’’38  PARTICIPATION IN CLINICAL RESEARCH IS NOT RISK FREE: Media coverage of ocular gene therapy has been

highly positive; like most coverage of genetics,39 it emphasizes benefits and provides minimal information on risks.25 While most published accounts of gene therapy have shown positive safety profiles, some risks are apparent. General risks for gene therapy, which remain hypothetical risks for ocular applications, include oncogenic risks from insertional mutagenesis and a severe immune response.40 Specific risks include surgical complications, loss of an eye owing to endophthalmitis, loss of remaining vision,2–4 and a theoretical risk of brain toxicity owing to integration of the viral vector in the optic nerve. Reported adverse events include a macular hole,4 foveal thinning,17 and retinal detachment.14 Other risks to participants include associated financial burdens and psychological stress. While disclosure of risks is an essential component of the informed consent process for clinical trial participation, urgency to access a trial may divert patient attention from the risks.34 Recommendation. When discussing possible participation in a clinical trial, clinicians should highlight that potential risks exist. Clinicians may direct patients to carefully consider and question descriptions of both magnitude and likelihood of risks during the process of informed consent.  POTENTIAL TREATMENT, NOT CURE:

If proven safe and efficacious, gene therapy may present a treatment but not a cure for patients who have already experienced vision loss. While gene therapy may restore the function of dormant yet viable photoreceptors and thereby improve visual

COMMUNICATING THE PROMISE FOR OCULAR GENE THERAPIES

411

FIGURE 1. Visual outcome perspectives of choroideremia gene therapy stakeholders and ocular gene therapy media representations.

outcome measures, unlike proposed cell therapies, it is not regenerative.17 The LCA trials demonstrate that there may be a therapeutic window for efficacy, with earlier intervention being better, especially if prior to the onset of retinal degeneration.8 Nevertheless, the media commonly represent gene therapy as a cure for inherited eye diseases.25 One popular book on LCA gene therapy went so far as to be titled The Forever Fix.41 Other stakeholder perspectives tend to be more nuanced. Participants in one choroideremia study anticipated outcomes that ranged from no benefit, through slowing or halting vision loss, to a cure for choroideremia (Figure 1).34 All stakeholder groups acknowledged the possibility of no benefit. However, although clinicians and advocacy organizations did not express expectations for a cure and considered slowing vision loss as a realistic outcome, patient perspectives ranged from halting vision loss to a cure. In other words, patients overestimated the potential benefits of gene therapy research, which represents a ‘‘therapeutic misestimation.’’35 Such overestimation of benefit may be ethically tolerable if its probability was difficult to convey or perceive,35 but in the case of ocular gene therapy, a cure is highly unlikely. Its long-term effects are unknown at present.8 Recommendation. It is important for clinicians to clearly communicate the spectrum of possible visual benefits of future gene therapies. Gene therapy is not regenerative, and therefore will not revive cells that have already degenerated. Thus, if approved by United States regulators as the first ocular gene therapy product following phase III clinical trials, Spark Therapeutics’ gene therapy for LCA will be a treatment, not a cure. Mounting evidence suggests that gene therapy may need to be readministered, or administered in combination with medications that may still be in development.12  TRANSLATIONAL TIMELINES ARE LENGTHY:

The road to the clinic for novel biotherapeutics is long and

412

challenging. Even for small-molecule drugs, it takes 10-14 years, with estimated costs in the billions, to move from preclinical studies to market authorization by a regulatory agency.42 Gene therapy has been hailed as 5 years away from clinical application since the 1990s,43 and media, clinicians, and patient advocates contribute to patient confusion by expressing vague timelines for its arrival in the clinic.25,34 The media often depict the promise of research without providing context of when the described benefits may be realized. They widen the gap between patient hopes for an imminent treatment and the clinical reality of limited therapeutic options for many conditions.44 For example, choroideremia patients were left uncertain about whether gene therapies would become available within their own therapeutic window for visual gain.25 Nevertheless, these patients wished to consider future therapeutic options, such as gene therapy, when making current disease management decisions. Contextualizing expected times (and uncertainties) from mutation identification to potential gene therapy clarifies media accounts that make a direct link between discovery of ‘‘blindness-causing genes’’ and treatments.45 The history of LCA gene therapy research is illustrative of timelines (Figure 2). The RPE65 mutation was identified in 199746; phase I/II human trials began in 20072 with current trials in phase III (NCT00999609). The gene therapy product may become the first approved in the United States, aided in part by financial and regulatory incentives that expedite approval for orphan drugs that treat serious conditions and fill unmet medical need.47 NightstaRx, for example, recently announced that it has received orphan drug status in both the United States and Europe for its choroideremia gene therapy product (http://www. nightstarx.com/). While it is a necessary precursor to clinical availability, regulatory approval is not the endpoint. Novel biotherapies must still be adopted into clinical settings and be paid for by public or private insurers.48 These therapies are often very expensive and must clear value assessments by cash-strapped health systems and hospitals.49 Recommendation. Patients wish to weigh future therapeutic options when making current disease management decisions. Consequently, clinicians should discuss research timelines in relation to their patients’ vision loss and prognoses. Clinicians can assist patients by providing realistic timelines and positioning current research within models of clinical translation. Valuable information includes the phases of clinical trials and their goals, regulatory approvals, insurance/health system coverage decisions, and eventual clinical adoption. Such context will assist patients in assessing the likelihood of a gene therapy within a therapeutically meaningful window for their vision loss.  CELEBRATING HOPES THAT ARE GROUNDED IN CURRENT CLINICAL REALITIES: The last 20 years have seen

tremendous advances in research for retinopathies including the identification of over 280 genes and loci

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FIGURE 2. Translational timeline of gene therapy for Leber congenital amaurosis (LCA).50–52 Colors indicate research groupings. Red [ Maguire/Bennett group: University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP); gene therapy product licensed by Spark Therapeutics. Blue [ Jacobson/Cideciyan group: University of Pennsylvania. Green [ Bainbridge group: University College, London.

underlying inherited retinal disorders.53 and a shift from basic science inquiry to targeted preclinical and clinical trials using gene transfer, stem cell, drug, and optogenetic approaches.54 These developments provide a landscape of hope, which is rooted in a ‘‘paradox of uncertainty’’55—positive clinical trials have the potential to transform current prognoses of vision loss but may equally be a source of anxiety or vulnerability. The latter arises because treatments may not become available within the limited therapeutic windows of patients. Reflecting on hope, Ruth McGovern, mother of 2 boys with adrenoleukodystrophy, an X-linked metabolic disorder targeted by gene therapy research, stated: ‘‘hope is uplifting and valuable when all around is uncertain for without hope the alternative for me would be despair.’’56 Hope both supports and is supported by disease management. But hope may also challenge pragmatic efforts to prepare for a prognosis of vision loss,34 including vocational and assistive technology, dietary supplementation, and social supports. Recommendation. These findings necessitate a communications approach that acknowledges patient hopes for possible therapeutic interventions, while grounding VOL. 160, NO. 3

expectations in current clinical realities. In other words, clinicians might employ a ‘‘plan for today, hope for tomorrow’’ message. Clinicians may employ a wellness-based approach, emphasizing enhancement in the emotional, psychological, and spiritual dimensions of quality of life in addition to hopes for physiological improvements.55

CONCLUSION OCULAR GENE THERAPY CLINICAL TRIALS ARE RAISING

hopes for treating a myriad of hereditary retinopathies. However, for most diseases, such therapies are many years in the future. We call for a clinical communications approach that respects and contextualizes patient hopes within current clinical and research realities. Clinicians should be prepared to counter overly optimistic messaging, especially that found in news media and on the Internet, with optimism tempered by evidence. Such communications will become increasingly important as novel gene and cell therapies advance through clinical development and will support the ethical translation of these fields.

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ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST and none were reported. This work was supported by an Alberta Innovates - Health Solutions, Canada CRIO Team Grant (Alberta Ocular Gene Therapy Team, Co-leads: I.M.M., T.B.), as well as by a Canadian Institutes of Health Research (CIHR) Emerging Team Grant, Rare Diseases (I.M.M., T.B.), and grants from the Foundation Fighting Blindness Canada and the Choroideremia Research Foundation, Canada. All authors attest that they meet the current ICMJE requirements to qualify as authors. The authors thank Mark Bieber and Zackariah Breckenridge, School of Public Health, University of Alberta, for compiling and annotating current ocular gene therapy clinical trials.

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44. Bubela T, Li M, Hafez M, Bieber M, Atkins H. Is belief larger than fact: expectations, optimism and reality for translational stem cell research. BMC Med 2012;10(1):133. 45. Cahill R. Scientists discover gene tied to profound vision loss. Available at https://www.uth.edu/media/story.htm? id¼f1d67f08-4d4c-40a8-a342-4bbef5d5e028. Accessed May 17, 2015. 46. Marlhens F, Bareil C, Griffoin JM, et al. Mutations in RPE65 cause Leber’s congenital amaurosis. Nat Genet 1997;17(2): 139–141. 47. Pariser AR, Slack DJ, Bauer LJ, Warner CA, Tracy LA. Characteristics of rare disease marketing applications associated with FDA product approvals 2006–2010. Drug Discov Today 2012;17(15-16):898–904. 48. Timmerman L. Gene therapy lurches ahead, sees thorny future questions on price. Available at http://www.xconomy.com/ national/2014/01/27/gene-therapy-lurches-ahead-sees-thornyfuture-questions-on-price/. Accessed March 23, 2015. 49. Bubela T, McCabe C. Value-engineered translation for regenerative medicine: developing bioetherapeutics that align with health-system needs. Am J Manag Care Diabetes 2014;22(Suppl 1):307–312. ¨ ber Retinitis pigmentosa und angeborene Amau50. Leber T. U rose. Archiv fu¨r Ophthalmologie 1869;15(3):1–25. 51. Aclend GM, Aguirre GD, Ray J, et al. Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 2001;28:92–95. 52. Cideciyan AV, Hauswirth WW, Aleman TS, et al. Vision 1 year after gene therapy for Leber’s congenital amaurosis. New Engl J Med 2009;361(7):725–727. 53. RetNet. Genes and mapped loci causing retinal diseases. Available at https://sph.uth.edu/RetNet/disease.htm. Accessed May 17, 2015. 54. Sahel J-A, Roska B. Gene therapy for blindness. Annu Rev Neurosci 2013;36:467–488. 55. Groopman JE. A strategy for hope: a commentary on necessary collusion. J Clin Oncol 2005;23(13):3151–3152. 56. McGowan R. Beyond the disorder: one parent’s reflection on genetic counselling. J Med Ethics 1999;25:195–199.

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Biosketch Shelly Benjaminy is a doctoral student at the National Core for Neuroethics at the University of British Columbia. She holds a Bachelor of Science degree with Specialization in Molecular Genetics, and a Master of Science degree in Health Policy Research from the University of Alberta. Ms. Benjaminy specializes in translational ethics and utilizes pragmatic empirical approaches to explore ethical, social and policy dimensions of developing biotechnologies.

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Biosketch Dr. Tania Bubela (BSc (Hons), PhD, JD) is Professor and Associate Dean (Research) in the School of Public Health, Canada. Her research program addresses barriers to the effective translation of new technologies arising from collaborative science networks in genomics, gene therapy, and stem cell biology, including ethical issues, effective communication of risks and benefits among stakeholder groups, commercialization and regulation.

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Communicating the promise for ocular gene therapies: challenges and recommendations.

To identify challenges and pose solutions for communications about ocular gene therapy between patients and clinicians as clinical research progresses...
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