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Development of Treatments
for Age-Related Macular Degeneration

Age-related macular degeneration

Working in the ophthalmologic field as a first step in developing iPSC regenerative medicineWorking in the ophthalmologic field
as a first step in developing iPSC regenerative medicine

The retina is a light-sensitive nerve layer (similar in function to the film in a camera), lining the inner surface of the human eye. In the retina, light signals are converted to electrical signals and transmitted to the brain via the optic nerve. Eventually, light signals are processed as vision in the visual cortex. In the center of the posterior pole of the human retina, there is a special region known as the “macula.” In the center of the macula is the fovea, 1.5 to 2 mm in diameter, where light entering through the lens is focused, and functions most importantly for visual acuity. Therefore, if macular function is impaired, sufficient visual acuity cannot be obtained even when other regions of the retina are healthy. When an older person is having vision problems because of an impaired macula due to aging, it is referred to as age-related macular degeneration (AMD). AMD is the leading cause of vision loss in the elderly in Western countries and the fourth cause of vision loss in Japan.

The number of patients with AMD has increased due to longer lifespans of the elderly and a westernized lifestyle, whereas the incidence of AMD was considered to be relatively low in Japan until recently. Currently, the prevalence of AMD in Japan is estimated at approximately 1 percent of the population aged 50 years or older and increases with age (Hisayama Town Study, 1998 and 2007).

There are two types of AMD, wet (neovascular or exudative) and dry (atrophic), with different etiologies but similar symptoms. Two kinds of tissues, retinal pigment epithelium and choroid, are closely related with the pathology of AMD. The retinal pigment epithelium (RPE) cells form a monolayer, which is localized between the neurosensory retina and the choroid to maintain homeostasis of the retina, especially the macula. The choroid, a well-vascularized tissue, is localized under the RPE cells and nourishes the RPE and retina so they function properly and maintain good visual acuity at the macula.

In wet AMD, the function of the photoreceptor cells is impaired because of abnormal neovascularization, which occurs from the choroid and spreads out below the RPE cells or between the RPE cells and the photoreceptor cells. The neovascularization is caused by RPE cell damage from various causes associated with aging. These new vessels ultimately lead to bleeding or blood component leakage.

In dry AMD, visual acuity is decreased due to age-related inflammation in RPE cells and their death that often leads to the loss of photoreceptor cells.

Pathology of age-related macular degenerationPathology of age-related macular degeneration

Therapeutic approach for AMD

Currently, some therapies are available for treating wet AMD. However, these therapies can ameliorate wet AMD by preventing progression and inducing regression of neovascularization. In many cases those effects are transient and require frequent re-treatment. Therefore, these therapies cannot lead to a fundamental solution while maintaining or improving visual acuity. At Present, no effective therapy for dry AMD is available.

Healios is committed to the development of a fundamental therapeutic approach for treating AMD using RPE cell suspensions or RPE cell sheets with RPE cells differentiated from human induced iPS cells (iPSC-RPEs).

step_16_eiPS-RPE products and therapeutic approaches

Healios is focusing on the development of a therapeutic approach for wet AMD that restores retinal function via transplantation of iPS-RPE cell suspension to recover and maintain the health of photoreceptor cells.

Subretinal transplantation of iPSC-RPE cellsSubretinal transplantation of iPSC-RPE cells

In addition to an RPE cell suspension, Healios is also moving forward with preparation of an RPE sheet product and developing a transplant procedure.

For dry AMD, healthy RPE cells can be implanted to replace unhealthy RPE cells in lesion areas where RPE cells have been lost due to inflammation or other pathologies associated with dry AMD.

Our current goal is to launch two forms of iPS cell–derived RPE products, suspensions and sheets, in order to manage various types of AMD cases and provide the best therapeutic options. Toward our goal, we will work closely with health regulatory agencies to obtain approval for these two iPS cell–derived RPE products.

The path to realization

The foundations for regenerative medicines are nearing completion.The foundations for regenerative medicines are nearing completion.

In September 2014, the first transplant of an iPS-RPE sheet for an AMD patient was performed in Japan.
This case, part of the “Clinical study of transplantation of autologous induced pluripotent stem cell–derived retinal pigment epithelium (RPE) cell sheets for exudative age-related macular degeneration (AMD)” (authorized by the Ministry of Health, Labour and Welfare in July 2013), was conducted jointly by Riken and the Foundation for Biomedical Research and Innovation, with the cooperation of Kobe City Medical Center General Hospital.

The clinical course for the patient is important, but we expect this case study to provide a tailwind for clinical use of iPSC regenerative medicines.

Along with the start of Japan’s Act on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products and Cosmetics, and the enforcement of amendments to Pharmaceutical Affairs Act, the regulatory environment in Japan has now been established for obtaining rapid approval for the regenerative medical field.

We at Healios will make day-to-day progress to bring those study results into clinical practice as cellular and tissue-based products while resolving various remaining challenges, such as the establishment of a stable manufacturing system for safe and effective therapies, to commercialize iPSC regenerative medicines.

(Reference data)
Current situation of AMD treatment

The number of AMD patients and medical care costs are estimated as below;

The number of AMD patients and medical care costs are estimated

(Sources)

  • ・We created morbidity data based on the web sites of the National Eye Institute, the Japan Intractable Diseases Information Center and the American Macular Degeneration Foundation (AMDF).
  • ・Estimated medical care costs was extracted from published pharmaceutical company data (Roche, Bayer, Novartis, Regeneron, Santen Pharmaceutical).

    Based on the sales total of Lucentis® and Eylea® (including sales totals for indications other than wet AMD)
    Converted as 110 JPY/USD and 1.12 USD/CHF