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IRV ARONS
With the first approval of a gene therapy for treating a genetic disorder
in the Western world, the future of gene therapy for treating ocular
disorders looks bright. Glybera (alipogene tiparvovec), developed by the
Dutch company UniQure, to treat a rare lipoprotein lipase deficiency
(LPLD), was approved by the European Medicines Agency last
November. 1
Glybera is the first gene therapy treatment approved in Europe, but the
fourth worldwide. We have seen two previous approvals in China in the
field of oncology, and one approval in Russia for peripheral arterial
disease. The most recent approval provides a good time to discuss the
status of gene therapy for ocular disorders.
I first learned about gene therapy in November 2010, when I was
introduced to a company called RetroSense and its research using gene
therapy for the treatment of retinitis pigmentosa and dry AMD. 2 Since
that first write-up, I have been closely following developments in this
exciting field.
So what is gene therapy? How does it work? What are the applications in
ophthalmology? Who is involved? What is the current status of the many
clinical trials now under way? What does the future hold? Here, Ill
provide answers.

WHAT IS GENE THERAPY AND HOW DOES IT


WORK?
Gene therapy is the addition of new genes to a patients cells to replace
missing or defective copies, to restore or impart a new function to
overcome a disease usually of genetic origin. Researchers typically
deliver new genes to cells using modified virus vectors, as viruses have
evolved as preferred vectors to deliver genetic materials to cells.
Irv Arons is a retired former consultant to the ophthalmic industry, who
writes a blog, Irv Arons Journal, which focuses on new technologies,
including stem cells and gene therapy, for treating retinal diseases. He
reports no financial interest in the products mentioned in this article.
His blog can be found at http://irvaronsjournal.blogspot.com/. He can
be contacted at iarons@erols.com.

Two decades of experimentation and trials have been undertaken, some


of which were hallmarked by catastrophic results. In 1999, for instance,
one patient suffering from a metabolic disease died in a gene therapy
clinical trial, and regulatory agencies have been cautious since. Now,
however, gene therapy is emerging as a viable means of treating ocular
diseases.
With regard to ocular gene therapy, Abelson et al. noted:
When other areas of the body receive gene therapy, rejection of viral

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capsids carrying the payload is a concern. The eye however, experiences


reduced chances of vector rejection, just as foreign tissue in the eye
experiences extended, if not indefinite survival, where it would be
rapidly rejected in other parts of the body.
The eye is also relatively easy to monitor, both for potential side effects
and for treatment benefit, with methods such as electroretinography,
visual acuity, optical coherence tomography, and perimetry.
Ophthalmoscopy and fundus photography also provide an easy way to
directly visualize and document therapeutic effects.
Over the past several years, the unlocking of the human genome and
the discovery that certain genes, or lack thereof or genetic defects
therein, can be the cause of certain diseases has led to the ability to
identify genes associated with retinal and other ocular diseases.
According to the eyeGene National Ophthalmic Disease Genotyping
Network, more than 100 ocular gene types have been identified, and the
number increases yearly.4
In gene therapy, the companies and research institutions doing the work
use a virus that has been stripped of its ability to replicate as the
delivery mechanism for the gene of interest. The nonpathogenic virus
vector of choice for many applications is a recombinant adenoassociated viral vector (rAAV). The identified gene for the particular
disease is loaded onto the virus, and this combination is then delivered
to the diseased tissue of interest.
To date, the genes for some 35 ocular disorders have been identified,5
and a few of these diseases will be discussed below. (Another source,
RetNet,5 the Retinal Information Network, lists many more genes that
have been mapped and identified, specifically for retinal diseases.)

APPLICATIONS IN OPHTHALMOLOGY AND


STATUS OF CLINICAL TRIALS
Table 1 (available online at www.retinalphysician.com) lists the
companies and university research centers that I have identified as
active in this field. The table also shows the virus vector delivery system
and the gene therapy products being utilized, the partners involved, and
the specific ophthalmic indications targeted.
In Table 2 (online), I list 17 ophthalmic diseases that are currently
either in clinical trials or in preclinical research. Table 3 (online) lists the
16 ongoing and completed clinical trials identified, including the clinical
sites and the numbers of patients treated to date. A live link to the
clinical trial is included for further access to information about each
clinical trial.
The four ocular diseases that have received the most attention are
Lebers congenital amaurosis (LCA), wet AMD, Stargardt disease, and
Usher syndrome.

Lebers Congenital Amaurosis


Lebers congenital amaurosis is a rare, inherited retinal degenerative
disease characterized by severe loss of vision at birth or during the first
decade of life. A variety of other eye-related abnormalities, nystagmus,
deep-set eyes, and sensitivity to bright light, also occur with this
disease. Some patients with LCA also experience central nervous system
abnormalities.
In treating LCA, the majority of the work has been focused on RPE65,
the RPE-specific 65-kDA protein that is involved in the conversion of
all-trans retinol to 11-cis retinal during phototransduction and that has
been implicated as a genetic defect in LCA. When loaded onto the AAV2
virus, the product becomes AAV2-RPE65.
One of the leading groups in research into the treatment for LCA has
consisted of Jean Bennett, MD, and Albert Maguire, MD, with their
ground-breaking work done at the University of Pennsylvania and
Childrens Hospital in Philadelphia. Once the gene responsible for Lebers
was identified in the late 1990s, Drs. Bennett and Maguire, who initially
worked on this project with Drs. Sam Jacobson, Gus Aguirre, Bill
Hauswirth, and Eric Pierce, initiated in 2007 one of the first clinical trials
for a retinal degeneration.6
Since then, they have undertaken two additional clinical trials and have
successfully treated more than a dozen children with Lebers, with most
showing improved vision. They have now treated at least four of these
children in their second eye.
A new study, from the Scheie Eye Institute at the University of

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Pennsylvania,7 indicated that although continuing signs of vision


improvement in clinical trials were shown following gene therapy
treatment, advancing degeneration of affected retinal cells was also
seen, both in LCA patients and animal models of the same condition.
We all hoped that the gene injections cured both components
re-establishing the cycle of vision and also preventing further loss of cells
to the second disease component, said Artur V. Cideciyan, PhD,
coinvestigator of the LCA clinical trial at Penn.
However, when the otherwise invisible cell layers of the retina were
measured by optical imaging in clinical trial participants serially over
many years, the rate of cell loss was the same in treated and untreated
regions. In other words, gene therapy improved vision but did not slow
or halt the progression of cell loss, commented Cideciyan.
These unexpected observations should help to advance the current
treatment by making it better and longer lasting, said Samuel G.
Jacobson, MD, PhD, principal investigator of the clinical trial. Slowing
cell loss in different retinal degenerations has been a major research
direction long before the current gene therapy trials. Now, the two
directions must converge to ensure the longevity of the beneficial visual
effects in this form of LCA.
Other institutions involved in studying Lebers include Hadassah Medical
(Israel), University College London, and the University of Pennsylvania,
with support from the NEI, the University of Nantes in France, and
Applied Genetic Technologies Corporation (AGTC).

Wet AMD
Another major area of emphasis in gene therapy is treatment of wet
AMD. Although anti-VEGF drugs are currently successfully treating wet
AMD, the cost and time involved in monthly or semimonthly injections
can be troublesome. A one-time treatment the promise of gene
therapy (the forever fix8) is attractive.
Several companies are at the forefront of research into the use of gene
therapy for wet AMD. These include Genzyme; Avalanche
Biotechnologies, working with the Lions Eye Institute of Perth, Australia;
and Oxford BioMedica, in partnership with Sanofi.
In wet AMD, VEGF plays a critical role because blockade of VEGF is
sufficient to suppress the development of choroidal neovascularization. A
variety of antiangiogenic proteins oppose the actions of proangiogenic
factors, such as VEGF. Gene transfer to augment expression of these
endogenous inhibitors or related engineered proteins is a potential
alternative to suppress CNV and avoid frequent intraocular injections.
Considerable preclinical and emerging clinical data suggest this approach
may be feasible.
The secreted extracellular domain of VEGF receptor-1, sFlt-1, is a
naturally occurring protein antagonist of VEGF formed by alternative
splicing of the pre-mRNA for the full-length receptor. Intraocular
injection of Ad.sFlt-1 strongly suppressed retinal or subretinal
neovascularization in mice
Genzyme has developed a VEGF-binding protein that consists of domain
2 of Flt-1 linked to a human immunoglobulin G1 (IgG) heavy chain Fc
fragment (sFLT01). Intravitreous injection of AAV2.sFLT01 is being
evaluated in a phase 1/2 clinical trial of wet AMD.9
At least 17 patients have been treated to date with safety demonstrated,
but no visual improvement results have been reported, in keeping with
normal clinical trial protocol.

Stargardt Disease
The progressive vision loss associated with Stargardt disease usually
starts between the ages of 6 and 12 years plateaus shortly afterward,
with rapid reduction in visual acuity.
The gene identified in the treatment of Stargardt disease is ABCA4. This
gene produces a protein involved in energy transport to and from
photoreceptor cells in the retina. Mutations in the ABCA4 gene produce a
dysfunctional protein that cannot perform its transport function. As a
result, photoreceptor cells degenerate and vision loss occurs.
Stargardt is being studied by Oxford BioMedica and Sanofi. They have an
ongoing phase 1/2a clinical trial under way, in both the United States at
the Casey Eye Institute in Seattle and at the Centre Hospitalier
Nationale dOphthalmologie des Quinz-Vingts in Paris. To date, 12
patients have been treated in cohorts 1 and 2, with cohort 3 under way

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at dose level 2.
Safety has been demonstrated for up to 12 months, but as is normal
procedure in clinical trials, no vision improvement results have yet been
reported.

Usher Syndrome 1b
Usher syndrome is a rare inherited condition characterized by both
hearing impairment and progressive vision loss and is a leading cause of
deaf-blindness. The vision loss is due to retinitis pigmentosa. Balance
may also be affected. Symptoms vary from person to person and
progress at different rates.
Three forms of Usher syndrome have been identified. Patients with type
1 have severe hearing loss and experience problems with balance, along
with RP. Those newborns with type 2 have moderate to severe hearing
impairment and symptoms of RP typically start shortly after
adolescence. Visual problems progress less rapidly than in Usher type 1,
and hearing loss usually remains stable.
Children with type 3, a rarer type, are usually born with good or only
mild hearing impairment. Their hearing and vision loss is progressive,
starting around puberty. Balance may also be affected.
One of the genes being studied for Usher Syndrome is MY07A, the basis
of UshStat in clinical trials by Oxford BioMedica and Sanofi. Their phase
1/2a clinical trial has treated the first cohort of three patients and has
received approval to proceed to cohort 2 at dose level 2. This trial is also
being conducted at the two locations noted above for Stargardt Casey
Eye and the Centre Hospitalier Nationale. Again, per protocol, no results
have yet been released.
In all, as shown in Table 3 (online), more than 80 patients have
received ocular gene therapy treatment, and the initial results that have
been reported (mostly for LCA) have shown some improvements in
vision, along with the safety of the treatment.

REMAINING QUESTIONS
To date, gene therapy in ophthalmology looks promising, in the sense
that some vision capacity has been restored, but several questions
remain. Will gene therapy deliver the holy grail of the forever fix or
something less? And with the first Western approval of a gene therapy
treatment (Glybera for LPLD), will ophthalmic therapies be next?
The question of cost also persists. One treatment of Glybera granted,
to treat a very rare disease with a worldwide population of only several
hundred may cost as much as $1.6 million.10 Nobody expects that
any of the proposed ophthalmic treatments will cost that much, as most
of the relevant disorders to be treated have populations several orders
of magnitude larger than the very rare disease treated by Glybera,
although certainly some rarer ocular disorders affect only a few hundred
to a few thousand individuals worldwide.

CONCLUSION
In 2012, officials with the Office of Cellular, Tissue and Gene Therapies
(OCTGT), Center for Biologics Evaluation and Research of the FDA,
stated , The recent history of gene therapy has been a mixture of
promise and disappointment Despite the setbacks of the past, the
OCTGT shares the enthusiasm of the field and is confident that ongoing
clinical investigations will lead to commercially available gene therapy
products that are safe and effective and advance the public health.11
RP

REFERENCES
1. Arons I. Gene therapy in ophthalmology update 15: First gene
therapy treatment. Irv Arons J. 2012 Nov 6. Available at:
http://tinyurl.com/GeneTherapy15. Accessed March 1, 2013.
2. Arons I. The use of gene therapy in treating retinitis pigmentosa and
dry AMD. Irv Arons J. 2012 Nov 6. Available at: http://tinyurl.com
/GeneTherapy-RP-AMD. Accessed March 1, 2013.
3. Abelson MB, Tzekov RT, Howe A. Gene therapy turns foes into
friends. Rev Ophthalmol. 2009 Aug 13. Available at:
http://www.revophth.com/content/d/therapeutic_topics/i/1213/c/22855.
Accessed March 1, 2013.

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4. National Eye Institute. eyeGENE - National Ophthalmic Disease


Genotyping Network: Genes and diseases. Available at:
http://www.nei.nih.gov/resources/eyegene/tableforgenes.asp. Accessed
March 1, 2013.
5. RetNet. Summaries of genes and loci causing retinal diseases.
Available at: https://sph.uth.edu/retnet/sum-dis.htm. Accessed March 1,
2013.
6. Bennett J, Maguire AM. The evolution of retinal gene therapy: from
DNA to FDA. Retin Today. 2011 October:55-58.
7. Penn Medicine. Penn study sheds light on the complexity of gene
therapy for congenital blindness. Available at:
http://www.uphs.upenn.edu/news/News_Releases/2013/01/blindness/.
Accessed March 1, 2013.
8. Lewis R. The Forever Fix: Gene Therapy and the Boy Who Saved It.
New York, NY; St. Martins Press; 2012.
9. Campochiaro PA. Gene transfer for neovascular age-related macular
degeneration. Hum Gene Ther. 2011;22:523-529.
10. Whalen J. Gene-therapy approval marks major milestone. Wall St J.
2012 Nov 2. Available at: http://online.wsj.com/article
/SB10001424052970203707604578095091940871524.html?KEYWORDS=glybera.
Accessed March 1, 2013.
11. Takefman D, Bryan W. The state of gene therapies: the FDA
perspective. Mol Ther. 2012;20:877-878.

Table 1. Gene Therapy Companies/Institutions


Active in Ophthalmology
Company/Instit

Platform

Product/Partner Application

Applied Genetic
Technologies
Corp. (AGTC)

AAV

AAV2-sFLT01 Genzyme

AAV2-RPE65 OHSU

- Univ of
Florida
- OHSU
- Univ of Br.
Col
- UPenn
- Univ of
Florida

Status

wet AMD

Phase I/II
NCT01024998

Lebers
Congenital
Amaurosis
(LCA)

Phase I/II
NCT00749957

X-linked
Retinoschisis

Pre-Clinical

Achromatopsia

Pre-Clinical

Glaucoma

Avalanche
Biotechnologies
Inc.

AAV

rAAV.sFlt-1 Lions Eye


(Australia)

Wet AMD

Phase I/II
NCT01494805

Ceregene

AAV

CERE-140
AAV-NT4

retinitis
pigmentosa
(RP)

Pre-Clinical

AMD
Childrens Hosp,
Philadelphia

AAV2

AAV2-hRPE65v2
- Univ of Iowa

Lebers
Congenital
Amaurosis
(LCA)

Phase I
NCT00516477
NCT01208389
(2nd eye)
Phase III
NCT00999609

Choroideremia
Copernicus
Therapeutics

EOS Neuroscience

AAV

Pre-Clinical

nanoparticle
delivery of genes
- Oklahoma
Health Services

Major retinal
diseases
rds (gene) RP

Pre-Clinical

Eos 013 -

retinitis
pigmentosa
(RP)
(optogenetic)

Pre-Clinical

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AMD (wet or
dry?)
Genable
Technologies

AAV

GT038

autosomal
dominant
retinitis
pigmentosa
(adRP)

Pre-Clinical

Genesolve Vision
Diagnostics

CVD Cure

L-Opsin

Color
Blindness

Pre-Clinical

GenVec

AAV

AdPEDF

wet AMD

Phase I*
*GenVec has
abandoned
this research
program

Hadassah Medical

AAV2

AAV2-hRPE65

LCA

Phase I
NCT00821340

Hemera
Biosciences

AAV2

HMR59

GA and Dry
AMD

Pre-clinical

Oxford Biomedica

LentiVector

RetinoStat Sanofi-Aventis
- Wilmer Eye
(Johns Hopkins
Univ)
- OHSU

wet AMD

Phase I
NCT01301443

diabetic
retinopathy
(DR)

IND prep.

StarGen Sanofi-Aventis
- OHSU
- Institute de
la Vision
(France)
UshStat Sanofi-Aventis
-OHSU
- Institute de
la Vision
(France)

ReGenX
Biosciences

NAV/AAV

Phase I/IIa
NCT01367444
Stargardts

RP/Usher
Syndrome
Type 1b

EncorStat Sanofi-Aventis

Corneal graft
rejection

Phase I/IIa
prep.

Glaucoma GT Mayo Clinic

chronic
glaucoma

IND prep

rAAV8 -

X-Linked
retinitis
pigmentosa
(RP)
Lebers
Congenital
Amaurosis
(LCA)

RetroSense

Targeted Genetics

AAV

AAV

RST-001 (Chop2)
(also known as
ChR2)

RPE65 -

(Now, AmpliPhi
Biosciences
Corporation)

Univ. College,
London/Moorfields
Eye Hospital

AAV

Phase I/IIa.
NCT01505062

AAV2-RPE65

Pre-Clinical

Pre-Clinical

retinitis
pigmentosa
(RP)
(optogenetic)

Pre-Clinical

dry AMD

Pre-Clinical

Lebers
Congenital
Amaurosis
(LCA)

Phase II*

Lebers
Congenital
Amaurosis

PhaseI/II
NCT00643747

*According to
my sources,
Targeted
Genetics made
the vector for
the
Moorfields/UCL
LCA trial and
have no
interest in
ocular
applications
going forward.

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(LCA)
Wellstat
Ophthalmics, Inc.
(Formerly Advanced
Vision Therapies,
Inc.)

AAV

AVT 101 -

dry AMD
wet AMD
diabetic
retinopathy
(DR)
retinitis
pigmentosa
(RP)

Univ of Southern
Calif.

Mx-dnG1

corneal
scarring

Phase I/II

Univ of Wisconsin

SCH-412499

glaucoma

Phase I

UPenn, UCLA, Univ


of Florida

Usher
Syndrome
Type 1b

Pre-Clinical

Univ of Michigan,
UPenn, Univ of
Florida NEI

X-linked
retinitis
pigmentosa
(RP)

Pre-Clinical

Choroideremia

Phase I/II
NCT01461213

Lebers
Congenital
Amaurosis
(LCA)

Phase I
NCT00481546

Imperial College
London, Oxford
Univ, Moorfields

AAV

rAAV2.REP1
-OHSU
-Nationwide
Childrens Hosp.

UPenn
UPenn
Univ of Florida

rAAV2-CBSB-hR
PE65
-NEI

Mass Eye & Ear

-NEI

Pre-clinical

Univ of Nantes

rAAV-2/4.hRPE65

Phase I/II
NCT01496040

Institute de la
Vision (Paris)
Friedrich Miescher
Instit (Basel)

AAV

King Khaled Eye


Hospital

AAV

Univ of Florida

AAV8

retinitis
pigmentosa
(RP)
(optogenetics)

Pre-Clinical

MERTK (gene)
-Univ Calif San
Diego
- Univ Florida
(produced the
vector - not
involved in
patient trials)

MERTK-related
autosomal
recessive RP

Phase I
NCT01482195

MFRP (gene)

arRP

Pre-Clinical

Irv Arons August 2012 (Version 13, Aug 9,


2012)
NCT - National Clinical Trial (ClinicalTrials.gov)

Table 2. Gene Therapy in Ophthalmology by


Application
Application

Company/Institution Status

Lebers
Applied Genetic
Congenital
Technologies
Amaurosis (LCA)
Childrens Hosp. Phil.

Clinical Trial

Phase I/II

NCT00749957

Phase I

NCT00516477
NCT01208389
NCT00999609

Phase I
Phase III
Hadassah Medical

Phase I

ReGeneX Biosciences

Pre-Clinical

Univ. College
London/Moorfields

Phase I/II

UPenn/Univ. of Florida Phase I


Mass Eye & Ear

Pre-Clinical

Univ. of Nantes

Phase I/II

Leber Hereditory Huazhong Univ.(China) Phase I


Optic

NCT00821340

NCT00643747

NCT00481546

NCT01496040
NCT01267422

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Neuropathy
Wet AMD

Genzyme

Phase I/II

NCT01024998

Avalanche
Biotechnologies/Lions
Eye (Perth)

Phase I/II

NCT01494805

Phase I

NCT01301443

Oxford
Biomedica/Sanofi
Dry
Hemera Biosciences
AMD/Geographic
Atrophy (GA)
RetroSense

Pre-Clinical

Achromatopsia

Applied Genetic
Technologies

Pre-Clinical

Choroideremia

Childrens Hospital
Philadelphia

Pre-Clinical

Imperial College
London/Oxford
Univ./Moorfields

Phase I/II

Color Blindness

Gensolve Vision
Diagnostics

Pre-Clinical

Diabetic
Retinopathy

Oxford Biomedica

IND-Prep

Stargardts

Oxford
Biomedica/Sanofi

Phase I/IIa NCT01367444

Corneal Graft
Rejection

Oxford
Biomedica/Sanofi

Phase I/IIa
Prep

Chronic
Glaucoma

Oxford
IND-Prep
Biomedica/Mayo Clinic
Univ. Of Wisconsin

Pre-Clinical

NCT01461213

Phase I

Corneal Scarring Univ. of Southern Calif. Phase I/II


Retinitis
Ceregene
Pigmentosa (RP)
EOS Neuroscience

X-linked
Retinoschisis

Pre-Clinical
Pre-Clinical

RetroSense

Pre-Clinical

Institute de la
Vision(Paris)/Friedrich
Mieshcer Institute
(Basel)

Pre-Clinical

Applied Genetic
Technologies

Pre-Clinical

ReGeneX

Pre-Clinical

Univ of
Michigan/UPenn/Univ of Pre-Clinical
Florida/NEI
Autosomal
Dominent RP
(adRP)

MERTK-related
autosomal
recessive RP

Genable Technologies

Pre-Clinical

Copernicus
Therapeutics

Pre-Clinical

King Khaled Eye


Hospital

Phase I

Univ. of Florida

Pre-Clinical

Usher Syndrome Oxford Biomedica


(1b)
UPenn/UCLA/Univ. of
Florida

NCT01482195

Phase I/IIa NCT01505062


Pre-Clinical

Irv Arons May 2012 (Version 4, 5/10/12)


Table 3. Gene Therapy in Ophthalmology Ongoing Clinical Trial Details
Disease State

Clinical Trial

Sponsor

Clinical Sites

Status

Number
Patients
to be
Treated

Number
Treated to
Date

Lebers
Congenital
Amaurosis
(LCA)

NCT00749957

Applied Genetic
Technologies

Casey Eye
(OHSU) - R*

Phase
I/II

12

NCT00516477

Childrens Hosp.
Phil

Childrens Hosp
(Phil) (Active,
not recruiting)

Phase
I

12

12

12

4+ (have

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NCT01208389

Childrens Hosp
(Phil) (Followup

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Phase
I

had second
eye treated)

nd

for 2 eye of
above) - R

NCT00999609

Childrens
Hosp (Phil) NYR*
Univ of Iowa
- NYR

Phase
III

24

NCT00821340

Hadassah Medical

Hadassah Med
-R

Phase
I

10

NCT00643747

Univ College
London

Moorfields Eye
Hosp - R

Phase
I/II

12

12+ (Phase
II has
started)

NCT00481546

UPenn/NEI

Shands
Childrens Hosp
(UFla) - R
Scheie Eye
Inst. (UPenn) R

Phase
I

15

NCT01496040

Univ of Nantes

Nantes
University
Hospital - R

Phase
I/II

Leber
Hereditory
Optic
Neuropathy
(LHON)

NCT01267422

Huazhong Univ
(China)

Tongji
Hospital, - R
Tongji
Medical
College, - R
Huazhong
University - R

Phase
I

Wet AMD

NCT01024998

Genzyme

Retinal
Consultants of
AZ - R
Johns
Hopkins
University - R
Ophthalmic
Consultants of
Boston - R
UMass
Medical School
-R

Phase
I

34

NCT01494805

Lions Eye
Institute
(Perth)/Avalanche
Biotechnologies

Lions Eye
Institute
(Perth) - R

Phase
I/II

48

NCT01301443

Oxford
BioMedica/Sanofi

Johns
Hopkins
University - R
Casey Eye
Institute
(OHSU)- NYR

Phase
I

18

9 (Cohort 3
completed)
Confirmatory
Dose Level
Study
Underway

Choroideremia

NCT01461213

University of
Oxford

Moorfields
Eye Hospital R
St Marys
Hospital,
Manchester
Univ - R
Oxford
Radcliffe
Hospitals - R
Eye Unit,
Southampton
University
Hospitals - R

Phase
I/II

12

61

Stargardts
Disease

NCT01367444

Oxford
BioMedica/Sanofi

Casey Eye
Institute
(OHSU)- R
Centre
Hospitalier
Nationale
dOphthalmolog
ie des QuinzeVingts (Paris) R

Phase
I/IIa

28

8 (In Cohorts
1&2, 4
treated for
severe
disease and
4 for less
severe)

3 (Observed
for 8 mo.)

4 (Cohort 3
underway at

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Current Status of the Use Of Gene Therapy in Ophthalmology

11 of 11

http://www.retinalphysician.com/articleviewer.aspx?articleID=108230

dose level 2)
MERTKrelated
autosomal
recessive RP

NCT01482195

King Khaled Eye


Hospital/King
Faisal Specialist
Hospital

King Khaled
Eye Specialist
Hospital - R

Phase
I

31

Usher
Syndrome
(1b)

NCT01505062

Oxford
BioMedica/Sanofi

Casey Eye
Institute -R
Centre
Hospitalier
Nationale
dOphthalmolog
ie des
Quinze-Vingts
(Paris) - NYR

Phase
I/IIa

18

3 (Cohort 1
Completed)
Cohort 2
Approved to
Proceed at
Dose Level 2

Irv Arons November 2012 (Version 5, November


20, 2012)
NYR - Not yet recruiting
R - Recruiting
1. Reported at ARVO 2012

Retinal Physician, Volume: 10 , Issue: April 2013, page(s): 30 - 32 75

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12/03/2014 1:47 AM