Path To A Cure

Since our inception in 2012, Achroma Corp has provided $397,144.00* in grants to DIRECTLY support research efforts in expediting a cure. This page highlights some of the work of prominent researchers currently involved with gene therapy. Gene therapy involves putting a normal copy of the affected gene back into cones of patients. Using Adeno-associated virus (AAV), the native (wild type) genes of the virus are removed and replaced with the gene of interest. This vector is then injected under the patient’s retina. Gene Therapy 101 is summarized in this article by Dr. Shannon Boye: click here to view

Sheep ACH Video: This fantastic video of sheep (affected with CNGA3 mutation) that were treated with gene therapy (subretinal-injection) as a result of collaboration between University of Florida, Hadassah-Hebrew University Medical Center, The Volcani Center, and the Hebrew University of Jerusalem. Special thanks to Dr. Hauswirth at the University of Florida for sharing it with Achroma Corp.

For each animal you see the ear tag before treatment and its poor performance navigating the maze. Then you see the same sheep (ear tag shown again) after treatment (just one eye) showing its performance markedly improved, actually very nearly normal.

Sheep video:

More about this study can be found HERE (click to read).

Banin E, Gootwine E, Obolensky A, Ezra-Elia R, Ejzenberg A, Zelinger L, Honig H, Rosov A, Yamin E, Sharon D, Averbukh E, Hauswirth WW, Ofri R.”Gene Augmentation Therapy Restores Retinal Function and Visual Behavior in a Sheep Model of CNGA3 Achromatopsia.”Mol Ther. 2015 23:1423-33 PMID:26087757

Research Articles

Gene Therapy in a Sheep Model of CNGA3 Achromatopsia: ARVO 2014 click here to view

History of Gene Therapy: Gene therapy rescues cone function in congenital Achromatopsia:
click here to view

We would like to acknowledge Drs. Andras Komaromy (Michigan St. U.), Gustavo Aguirre (U. Penn) and William Hauswirth (U. Florida), for providing this video. This video demonstrates the effects of gene therapy in treated dogs.

Dog ACH video:

MeiraGTx is a clinical-stage gene therapy company focused on developing potentially curative treatments for patients living with serious diseases. In partnership with leading experts around the world, we are developing investigational gene therapies for the treatment of multiple inherited retinal diseases (IRDs). We are currently conducting clinical trials of investigational gene therapies for the treatment of achromatopsia (ACHM) caused by mutations in either the CNGB3 gene or the CNGA3 gene. We are proud to have Janssen Pharmaceuticals, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson as our development partner as part of a global collaboration to develop and commercialize gene therapies for the treatment of IRDs. Janssen established its Retinal Disease portfolio in 2018 to develop transformational therapies and platforms that restore and preserve vision. The portfolio expands Johnson & Johnson’s already broad ophthalmic footprint and includes a pipeline of innovative treatments for inherited retinal diseases, as well as more common retinal diseases affecting millions of people worldwide.

Investigational Gene Therapies for the Treatment of Achromatopsia (ACHM):

AAV-CNGB3, a gene therapy treatment designed to restore cone function, is delivered via subretinal injection to the area of the eye where most of the cones in the retina are located.

Clinical Trial Details: https://www.clinicaltrials.gov/ct2/show/NCT03001310

AAV-CNGA3, a gene therapy treatment designed to restore cone function, is delivered to the cone receptors at the back of the eye via subretinal injection. It was designed with a synthetic promoter associated with strong gene expression to account for the larger amount of protein needed to restore cone function in patients with a CNGA3 gene mutation.

Clinical Trial Details: https://clinicaltrials.gov/ct2/show/NCT03758404

Natural History Study: We also have an ongoing prospective natural history study for patients with achromatopsia.

Natural History Study Details: https://clinicaltrials.gov/ct2/show/NCT04124185

For more information about our ACHM clinical programs, please visit the MeiraGTx website https://meiragtx.com/patients-families or email patients@meiragtx.com

Joseph Carroll, Ph.D.
Richard O. Schultz, MD / Ruth Works Professor of Ophthalmology Professor of Ophthalmology & Visual Sciences, Biophysics, and Cell Biology, Neurobiology and Anatomy Director, Advanced Ocular Imaging Program
Medical College of Wisconsin

The success of gene therapy relies on the presence of intact (albeit non-functioning) cone photoreceptors to treat. Many traditional imaging techniques, such as fundus photography, do not provide the resolution needed to determine whether these cells are present in the living human eye. The Advanced Ocular Imaging Program (AOIP) at the Medical College of Wisconsin is home to a variety of high-resolution imaging tools, such as adaptive optics scanning light ophthalmoscopy (AOSLO), which enables visualization of the retina on a cellular scale. Using this technique, we discovered that, although there are generally fewer cone cells in the retinas of patients with CNGB3-associated achromatopsia, the cone inner segments remain intact.[Langlo, 2016]

[caption: Shown are foveal images from two patients with CNGB3 achromatopsia, taken using “split-detection” AOSLO. Each large bump/divot represents an individual cone cell. The image on the left shows a very sparse mosaic of cones at the fovea, whereas the image on the right shows contiguous cone packing. This demonstrates the high variability in number and packing of cells is highly variable – the impact this may have on treatment success remains to be determined.]

Follow-up imaging of the same patients over multiple visits has revealed that cell structure remains generally stable over time,[Langlo, 2017; Hirji, 2018] which suggests that patients may be viable candidates for therapy throughout adulthood. We also found that there is a high degree of symmetry between the two eyes of the same patient,[Mastey, 2018] which means that the untreated eye should provide a good control for monitoring changes due to therapeutic efforts. We have also made important advances towards improving our techniques for quantifying the photoreceptors in achromatopsia, using the latest deep-learning algorithms[Cunefare, 2018].

We continue to improve our imaging and analysis techniques – in order to achieve this, we are striving to image as many patients as possible for high-resolution retinal imaging. You can learn more about our research or volunteer directly at www.mcw.edu/AOIP/Participate/How-to-volunteer.htm Patients must be aged five years or above. Travel costs to and from Milwaukee for imaging may be reimbursed.

Dr. Carroll’s work on achromatopsia has been funded by Achroma Corp, the National Eye Institute, Foundation Fighting Blindness, Research to Prevent Blindness, and numerous individual donors to the Advanced Ocular Imaging Program.

Research Articles

Cunefare, D., Langlo, C.S., Patterson, E.J., Blaum S., Dubra, A., Carroll, J., Farsiu, S. “Deep learning based detection of cone photoreceptors with multimodal adaptive optics scanning light ophthalmoscope images of achromatopsia” Biomedical Optics Express, 9(8): 3740-3756 (2018).

Hirji, N., Georgiou, M., Kalitzeos, A., Bainbridge, J.W., Kumaran, N., Aboshiha, J., Carroll, J., Michaelides, M. “Longitudinal assessment of retinal structure in achromatopsia patients with long-term follow-up” Investigative Ophthalmology & Visual Sciences, 59(15): 5735-5744 (2018).

Langlo, C.S., Erker, L.R., Parker, M., Patterson, E.J., Higgins, B.P., Summerfelt, P., Razeen, M.M., Collison, F.T., Fishman, G.A., Kay, C.N., Zhang, J., Weleber, R.G., Yang, P., Pennesi, M.E., Lam, B.L., Chulay, J.D., Dubra, A., Hauswirth, W.W., Wilson, D.J., Carroll, J.; ACHM-001 study group. “Repeatability and longitudinal assessment of foveal cone structure in CNGB3-associated achromatopsia” Retina, 37(10): 1956-1966 (2017).

Langlo, C.S., Patterson, E.J., Higgins, B.P., Summerfelt, P., Razeen, M.M., Erker, L.R., Parker, M., Collison, F.T., Fishman, G.A., Kay, C.N., Zhang, J., Weleber, R.G., Yang, P., Wilson, D.J., Pennesi, M.E., Lam, B.L., Chiang, J., Chulay, J.D., Dubra, A., Hauswirth, W.W., Carroll, J., ACHM-001 Study Group. “Residual foveal cone structure in CNGB3-associated achromatopsia” Investigative Ophthalmology & Visual Science, 57(10): 3984-3995 (2016).

Mastey, R., Litts, K.M., Langlo, C.S., Patterson, E.J., Strampe, M.R., Carroll, J. “Interocular Symmetry and Repeatability of Foveal Outer Nuclear Layer Thickness in Congenital Achromatopsia” bioRxiv (2018).

Joseph Carroll, Ph.D.
The Medical College of Wisconsin
Department of Ophthalmology
925 North 87th Street
Milwaukee, WI 53226-4812

Office Phone: (414) 955-2052
FAX: (414) 955-6690
Email: jcarroll@mcw.edu
Website: https://www.mcw.edu/departments/ophthalmology-eye-institute/faculty/joseph-carroll-phd


Dr. Joseph Carroll and Raymond	An image of Raymond’s cones (large bumps) within his retina as seen by Dr. Carroll’s split-detector adaptive optics.

Applied Genetic Technologies Corporation (AGTC)

Applied Genetic Technologies Corporation (AGTC) is a clinical-stage biotechnology company developing transformational genetic therapies for inherited retinal diseases, such as achromatopsia.

AGTC is currently conducting two separate Phase 1/2 clinical trials to evaluate the safety and efficacy of gene therapy product candidates for the two most prevalent causes of achromatopsia: a genetic mutation in either the CNGB3 or CNGA3 genes. Together, these two mutations account for up to 75% of the achromatopsia population.

Gene therapy is the process of modifying a person’s cells by adding a functional copy of the mutated gene that is causing the disease. The new functional copy allows an individual’s body to produce proteins to treat or prevent genetic conditions. A single treatment can provide long lasting benefits, potentially leading to a better quality of life. To learn more about gene therapy, check out AGTC’s animation: https://www.youtube.com/watch?v=xOQFJJOBGM0

AGTC uses a virus called adeno-associated virus, or AAV, as a way to deliver a normal copy of a missing or broken CNGB3 or CNGA3 gene. AAV is a safe virus that has never been known to cause disease. In order to use AAV for gene therapy, the two native AAV viral genes are removed and replaced by a copy of a normal human CNGB3 or CNGA3 gene to create an AAV vector. After the AAV vector enters a cell, the normal human gene in the vector directs the cell to make a normal version of the missing or broken protein, using the cell’s natural protein-making capabilities.

If you are a patient, caregiver or healthcare professional and are interested in more information about one of these trials please contact us at advocacy@agtc.com, or visit:

ACHMB3 Achromatopsia Phase 1/2 Clinical Trial (ClinicalTrials.gov Identifier: NCT02599922)

ACHMA3 Achromatopsia Phase 1/2 Clinical Trial (ClinicalTrials.gov Identifier: NCT02935517)

For more on AGTC’s achromatopsia research and progress, visit https://agtc.com/programs/achromatopsia/

* As of January 2022