Sub-retinal Transplantation of hESC Derived RPE(MA09-hRPE)Cells in Patients With Stargardt's Macular Dystrophy

This study is a Phase I/II, open-label, non randomized, sequential, multi-center clinical
trial. There will be 5 cohorts, the 4 low vision cohorts will contain 3 patients, the better
vision cohort will contain 4 patients. The enrolled cohorts will be as follows:

Three SMD patients- 50,000 MA09-hRPE cells transplanted

Three SMD patients- 100,000 MA09-hRPE cells transplanted

Four Better Vison SMD patients- 100,000 MA09-hRPE cells transplanted

Three SMD patients- 150,000 MA09-hRPE cells transplanted

Three SMD patients- 200,000 MA09-hRPE cells transplanted

Patients will be enrolled sequentially, and within each cohort of 3 patients, each patient's
clinical course over the first 6 weeks following cell transplantation will be reviewed by an
independent (DSMB) before enrollment is opened for the next 2 patients. A full safety
assessment of all 3 patients in each cohort will be made by the DSMB when the 3rd patient in
each cohort completes 4 weeks of follow-up, and before the first patient in the next cohort
receives a cell transplant. The exception is the better vision group where all patients may
be enrolled once DSMB approval has been received.

Each cohort will be enrolled sequentially in turn, with the exception of the better vision
cohort which may be enrolled in parallel with the other cohorts.

The day of the cell implantation will be Day 0, and patients will remain in the study until
the last visit at 12 months.

Inclusion Criteria:

- Adult male or female over 18 years of age.

- Clinical diagnosis of advanced SMD.

- If known, the patient's genotype will be recorded in the medical history, if unknown,
patient will allow for the submission of a sample for genotyping.Clinical findings
consistent with SMD.

- The visual acuity of the eye to receive the transplant will be no better than 20/400.
The visual acuity of the eye in the better vision cohort to receive the transplant
will be no better than 20/100.

- The visual acuity of the eye that is not to receive the transplant will be no better
than 20/400 for the worse vision patients and no worse than 20/100 for the better
vision patients.

- Peripheral visual field constriction documented on standard kinetic visual field
testing.

- Electrophysiological findings consistent with SMD.

- Medically suitable to undergo vitrectomy and subretinal injection.

- Medically suitable for general anesthesia or waking sedation, if needed.

- Medically suitable for transplantation of an embryonic stem cell line:

- Normal serum chemistry (sequential multi-channel analyzer 20 [SMA- 20]) and
hematology (complete blood count [CBC], prothrombin time [PT], and activated partial
thromboplastin time [aPTT]) screening tests.

- Negative urine screen for drugs of abuse.

- Negative human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV)
serologies.

- No history of malignancy,with the exception of successfully treated basal cell or
squamous cell carcinoma of the skin.

- Negative cancer screening within previous 6 months:

- complete history & physical examination;

- dermatological screening exam for malignant lesions;

- negative fecal occult blood test & if over age 50 years, negative colonoscopy within
previous 7 years;

- negative chest roentgenogram (CXR);

- normal CBC & manual differential;

- negative urinalysis (U/A);

- normal thyroid exam;

- if male, normal testicular examination; if over age 40, digital rectal examination
(DRE) and prostate specific antigen (PSA);

- if female, normal pelvic examination with Papanicolaou smear; and

- if female, normal clinical breast exam and if 40 years of age or older, negative
mammogram.

- If female and of childbearing potential, willing to use two effective forms of birth
control during the study.

- If male, willing to use barrier and spermicide contraception during the study.

- Willing to defer all future blood, blood component or tissue donation. -Able to
understand and willing to sign the informed consent.

Exclusion Criteria:

- History of malignancy,with the exception of successfully treated basal cell or
squamous cell carcinoma of the skin.

- History of myocardial infarction in previous 12 months.

- History of diabetes mellitus.

- Any immunodeficiency.

- Any current immunosuppressive therapy other than intermittent or low dose
corticosteroids.

- Serologic evidence of infection with Hepatitis B, Hepatitis C, or HIV.

- Current participation in any other clinical trial.

- Participation within previous 6 months in any clinical trial of a drug by ocular or
systemic administration.

- Any other sight-threatening ocular disease.

- Any chronic ocular medications.

- Any history of retinal vascular disease (compromised blood-retinal barrier.

- Glaucoma.

- Uveitis or other intraocular inflammatory disease.

- Significant lens opacities or other media opacity.

- Ocular lens removal within previous 3 months.

- If female, pregnancy or lactation.

- Any other medical condition, which, in the Investigator's judgment, will interfere
with the patient's ability to comply with the protocol, compromises patient safety,
or interferes with the interpretation of the study results.