Clinical trial for autologous bone marrow stem cells as treatment for AMD & RP shows promise

A phase 1 clinical trial utilizing human bone marrow CD34+ stem cells for patients with retinal vascular occlusion, hereditary or non-exudative age-related macular degeneration (AMD), or retinitis pigmentosa (RP) has shown safety and feasibility.


Currently, there are many research studies and clinical trials on-going to study the effectivness of stem cells as treatment options for retinal diseases such as AMD & RP. Differentiated retinal pigment epithelial cells derived from embryonic stem cells and inducible pluripotent stem cells have demonstrated to slow progression of retinal degeneration when injected into the subretinal space. However, this therapy requires systemic immunosuppressive therapy (possibly long-term) to minimize rejection of such cells by the patient's body. Furthermore, these stem cells are potentially teratogenic, raising long-term safety concerns.

Bone marrow (BM) contains a high concentration of adult stem cells that appear to play an important role in tissue maintenance and repair. Among the cells in human BM, much attention has been on CD34+ cells, which have been safely used for BM transplantation in clinical trials of coronary heart disease and other conditions.

Such CD34+ cells have been studied in animal studies as potential therapy for degenerative or ischemic retinal conditions. Intravitreally injected CD34+ cells have been demonstrated to migrate into the retina and home into the damaged retinal vasculature or neuronal tissue. Such cells have been detected in mouse retina as long as six months following injection with no associated safety issues.

Study: This study, conducted at the University of California Davis Eye Center, and published in the Investigative Ophthalmology & Visual Science, describes the preliminary observations of the first clinical trial exploring the safety and feasibility of using intravitreally injected autologous BM CD34+ cells to treat irreversible degenerative or ischemic retinal conditions such as retinal vascular occlusion, hereditary or non-exudative age-related macular degeneration, or retinitis pigmentosa. All patients were young adults except for the two AMD subjects (age range 23 to 85 years, mean of 48 years). All had advanced vision loss in the study eye with baseline bestcorrected visual acuity (BCVA) of 20/200 to 20/800. One subject had combined central retinal artery and venous occlusion, two others has Stargardt's disease, one patient had retinitis pigmentosa, while two others had advanced non-exedative (dry) macular degeneration. 

The CD34+ cells were isolated from the mononuclear cellular fraction of the BM aspirate and injected intravitreally into the eye. After the injection, in addition to regular ophthalmic examinations, serial tests included microperimetry/perimetry, fluorescein angiography, electroretinography (ERG), optical coherence tomography (OCT), and adaptive optics-OCT were performed over a six-month follow-up.

Outcome: A mean of 3.4 million (range of 1 to 7 million) CD34+ cells were isolated and injected per eye. The therapy was well-tolerated with no intraocular inflammation or hyper-proliferation. Best-corrected visual acuity and full-field ERG showed no worsening after six months. Clinical examination also showed no worsening during follow-up except among AMD subjects where mild progression of geographic atrophy was noted in both the study eye and contralateral eye at six-month follow-up, concurrent with some possible decline on multifocal ERG and microperimetry. Cellular in-vivo imaging using adaptive optics-OCT showed changes suggestive of new cellular incorporation into the macula of hereditary macular degeneration study eye.

Improvement in BCVA ranged from 0 to 11 lines in the ETDRS (Early Treatment for Diabetic Retinopathy Study) visual acuity chart during the six- month follow-up (mean improvement of three lines). Improvement of two or more lines of BCVA (i.e. 10 letters or more) was noted in four of six study subjects during the course of the study. The improvement in BCVA was larger in patient with retinal vascular occlusion when compared to the other subjects who had retinal degenerative conditions. The time course of improvement varied among the subjects. However, some improvement in measurement of BCVA was noted in all subjects by one-month follow-up. Most of the improvement was sustained during the six-month follow-up period with some fluctuations. However, the final BCVA at six-month follow-up usually was within one line of best-measured visual acuity during the follow-up period.

The best visual acuity improvement was observed in the patient with occlusion with the patient improving from 20/800 at base to 20/63 at 6 months (20/40 at 3 months). The two Stargardt's patients improved from 20/200 in both patients to 20/125 and 20/160 respectively, while the two AMD patients improved from 20/200 to 20/80 and 20/200 respectively.

clinicaltrials.gov