Statement on Cell and Gene Therapy Research

Cell therapy research

Research on cell-based therapies offers new avenues for the development of therapeutic strategies for diseases in which damage to or loss of particular types of cells in the eye causes vision loss. The cells impaired or lost in these diseases often cannot be fixed or replaced, and many of these diseases are currently incurable. The development of therapies involving transplantation of stem cells or other cell types could lead to the rescue of dysfunctional cells or possibly the replacement of lost cells including but not limited to: corneal endothelium in corneal dystrophies, trabecular meshwork cells and retinal ganglion cells in glaucoma, retinal photoreceptors and pigment epithelium in inherited retinal degenerations and age-related macular degeneration, lacrimal gland cells in dry eye disease, and retinal and choroidal capillary endothelium in diseases such as diabetic retinopathy.

Collectively, these diseases currently account for a large portion of irreversible vision loss in both developed and developing nations. Existing therapies for them have shortcomings including suboptimal efficacy, risk of side effects, and high cost. Since many of these conditions develop or become more severe with age, the magnitude of the problem will increase as we all live longer.

Gene therapy research

Gene therapies are another group of promising treatment strategies. Based on advances in molecular genetics including the sequencing of the human genome during the last half century, gene therapies aim to cure inherited diseases by addressing their underlying genetic cause. Approaches to achieve this goal include gene augmentation therapy, in which a normal copy of the affected gene is added to ocular cells, often via use of a viral delivery vector. Genome editing, the goal of which is to correct the causative mutations in endogenous genes in situ, is another promising approach to treat genetic diseases.

Any monogenic blinding disease for which the causative genetic mutations are known has the potential to be effectively treated by gene therapy, including inherited retinal degenerations, such as those traditionally known as retinitis pigmentosa and Leber congential amaurosis. Patients with common complex diseases such as age-related macular degeneration and glaucoma, for which genetic variants increase the risk of disease, may also benefit from gene therapies in the future.

Potential benefits and risks

The Association for Research in Vision and Ophthalmology (ARVO) strongly supports technological developments and policies that enable and encourage all facets of cell and gene therapy research.

Cell and gene therapies are broadly used in biomedical research, including in clinical trials. However, the long-term safety and efficacy of these therapies remain to be fully explored. Additional research is needed for more of these potential therapies to become a reality. For example, we need to determine the specific mechanisms that control the differentiation of stem cells into particular cell types and the mechanisms by which they exchange material with host cells or integrate into the damaged eye. The safety and specificity of gene therapy approaches, including genome editing, needs to be further explored via studies of vector specificity and off-target effects. Improving the safety and efficiency of all of these methods will be valuable for delivering successful treatments to eye tissues.

Eye and vision scientists have performed lab-based translational research on gene and cell therapies, the results of which have led to many preclinical and clinical studies of these approaches for the treatment of ocular diseases. The December 2017 FDA approval of a gene augmentation therapy for one genetic form of inherited retinal degeneration is encouraging, and highlights the importance of these studies for development of new treatments that may help patients in the near future. However, currently there are no FDA-approved cell therapies and other gene therapies are still in the pre-clinical or clinical trial stages. Hence, patients and families should be aware that all clinical trials should be performed only in clinical research facilities that adhere to good clinical practice (GCP) guidelines and Institutional Review Board oversight. No fees should be requested for patients to participate except co-pays on “standard care” aspects of the patient's care. Study consent forms and related materials should be provided in formats that patients with visual impairment can access using assistive devices as required. Should patients consider enrolling into a stem cell or gene therapy research trial, patients and their families should fully understand the risks and possible benefits, and have sufficient time to consider these and to discuss the study with family members and other medical professionals before making a decision.

Approved: ARVO Board of Trustees – April 28, 2018