Blind World

First Drug Therapy for RP to Enter Human Safety Studies.

Editor's Note: Included with this article, is a preface, written by Gislin Dagnelie, and two abstracts,, following this article, which were also provided by Mr. Dagnelie.
-- Blind World.

By: Gislin Dagnelie.

This is an informative message from the Foundation Fighting Blindness, regarding the upcoming Neurotech trial.

The message does not provide specific results in RP-affected animals, but I have added two abstracts I found on Medline, one positive, the other cautionary.

The first abstract, from researchers working at the Neurotech company that is sponsoring the upcoming trial, shows that the retina in dogs with a retinal degeneration *looks* better after treatment with this form of growth factor release through modified RPE cells.

The second abstract reports that normal mice and mice with a retinal degeneration lost a significant fraction of their ERG amplitude, an important measure of retinal function (although it does not necessarily mean that the mice also saw less, or would lose vision more quickly).

Clearly, the clinical trial outcome could go either way, and it seems appropriate that this first trial will only involve patients with wevere vision loss.

[End of Preface.]

July 25, 2003.
The Foundation Fighting Blindness (FFB).
Press Release.

The Foundation Fighting Blindness recently learned that the U.S. Food and Drug Administration (FDA) approved an application from the biotechnology company Neurotech, to begin a phase 1 human clinical trial to test the safety of a delivery device containing a drug to treat patients with end-stage Retinitis Pigmentosa (RP). Clinical testing is scheduled to begin in the fall of 2003.

This safety study represents the first clinical trial of a drug therapy for RP.

One of the major challenges to treatment of retinal disease has been the ability to deliver therapeutic drugs directly to the retina.

Neurotech, based in France and Rhode Island, developed Encapsulated Cell Technology (ECT), which enables controlled, continuous, long-term delivery of a drug called ciliary neurotrophic factor (CNTF) in patients with end-stage RP.

The Foundation Fighting Blindness (FFB) was an early supporter of the use of this technology for retinal diseases.

Dr. Gerald Chader, Chief Scientific Officer of FFB said, “Today’s announcement is one we’ve all been anxiously awaiting. CNTF and several other drug therapies have shown promise in a wide variety of animal models with RP. However, none of these drugs can pass through the blood/retina barrier, making traditional drug delivery with systemic injections or pills ineffective. Neurotech’s implantable ECT device may have at last broken through this previously formidable barrier.”

The ECT device is a testament to The Foundation’s perseverance in advancing retinal disease therapies. The ECT device was originally developed for use in treating Lou Gehrig’s disease and cancer. It was during these studies that FFB realized that the ECT might be adaptable to treat diseases of the retina. FFB encouraged Neurotech to test the device with CNTF in RP animal models. Through FFB’s innovative Medical Therapy Program, which reaches out to industry to encourage and foster vision research, FFB provided funding to support these important tests.

ECT consists of a very small capsule containing retinal pigment epithelial cells (RPE) that have been genetically modified to produce CNTF. The capsule has very small pores that allow oxygen and nutrients to diffuse in to sustain the RPE cells and also allow CNTF to diffuse out. The tiny pores prevent the modified RPE cells from escaping and protect the cells from the body’s immune system.

CNTF was chosen for its potent ability to delay the death of retinal photoreceptor cells in animal studies.

Because CNTF has not been tested in patients before, the first phase of this clinical trial will test the drug and the ECT device in 10 pre-selected patients with end-stage RP. In this way, the safety of the treatment can be evaluated without risk to existing vision. If all goes well in this phase I safety study, a phase II trial would then test the ability of the treatment to preserve vision in sighted RP patients. The timing of future trials is not yet known, and at this time patients are not being selected for future trials.

ECT and other emerging drug delivery devices could open the door for several survival factors that, like CNTF, have shown promise in treating the entire spectrum of retinal degenerative diseases. We hope to soon see other drug therapies join CNTF in clinical trials. There’s still more work ahead, but The Foundation’s efforts are clearly bearing fruit.

The Foundation Fighting Blindness' Mission

FFB is dedicated to finding the causes, preventions, treatments and cures for retinal degenerative diseases, including retinitis pigmentosa (RP), macular degeneration, Usher syndrome and others. FFB funds 155 research projects at 55 prominent institutions around the world and, as part of its mission, works with companies and other research entities to help advance research.

[Start of Abstract 1.]

Invest Ophthalmol Vis Sci. 2002 Oct;43(10):3292-8

Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa.

Tao W, Wen R, Goddard MB, Sherman SD, O'Rourke PJ, Stabila PF, Bell WJ, Dean BJ, Kauper KA, Budz VA, Tsiaras WG, Acland GM, Pearce-Kelling S, Laties AM, Aguirre GD.

Neurotech USA,
Lincoln, Rhode Island 02865,

PURPOSE: The objective of the present study was to evaluate the therapeutic efficacy of ciliary neurotrophic factor (CNTF) delivered through encapsulated cells directly into the vitreous of the eye in an rcd1 canine model of retinitis pigmentosa.

The dose-range effect of the treatment was also investigated.

METHODS: Polymer membrane capsules (1.0 cm in length and 1.0 mm in diameter) were loaded with mammalian cells that were genetically engineered to secrete CNTF. The cell-containing capsules were then surgically implanted into the vitreous of one eye of rcd1 dogs

at 7 weeks of age, when retinal degeneration is in progress but not complete. The contralateral eyes were not treated. The capsules remained in the eyes for 7 weeks. At the end of the studies, the capsules were explanted, and CNTF output and cell viability were evaluated.

The eyes were processed for histologic evaluation.

RESULTS: In each animal, the number of rows of photoreceptor nuclei in the outer nuclear layer (ONL) was significantly higher in the eye that received a CNTF-secreting implant than in the untreated contralateral eye.

No adverse effects were observed on the retina in the treated eyes. The explanted capsules produced a low level of CNTF. The cells in the capsules remained viable and densely distributed throughout.

CONCLUSIONS: CNTF delivered through encapsulated cells directly into the vitreous of the eye protects photoreceptors in the PDE6B- deficient rcd1 canine model. Furthermore, sparing of photoreceptors appeared dose-dependent with minimum protection observed at CNTF doses of 0.2 to 1.0 ng/d. Incrementally greater protection was achieved at higher doses. The surgically implanted, cell-containing capsules were well tolerated, and the cells within the capsule remained viable for the 7-week implantation interval. These results suggest that encapsulated cell therapy may provide a safe and effective strategy for treating retinal disorders in humans.

[End of Abstract 1.]

[Start of Abstract 2.]

Gene Ther. 2003 Mar;10(6):523-7

Intraocular gene delivery of ciliary neurotrophic factor results in significant loss of retinal function in normal mice and in the Prph2Rd2/Rd2 model of retinal degeneration.

Schlichtenbrede FC, MacNeil A, Bainbridge JW, Tschernutter M,
Thrasher AJ, Smith AJ, Ali RR.
Department of Molecular Genetics, Institute of Ophthalmology, University College London, UK.

Intraocular delivery of a variety of neurotrophic factors has been widely investigated as a potential treatment for retinal dystrophy (RD). The most commonly studied factor, ciliary neurotrophic factor (CNTF), has been shown to preserve retinal morphology and to promote cell survival in a variety of models of RD.

In order to evaluate CNTF as a potential treatment for RD, we used the Prph2(Rd2/Rd2) mouse. CNTF was expressed intraocularly using AAV-mediated gene delivery either by itself or, in a second treatment group, combined with AAV-mediated gene replacement therapy of peripherin2, which we have previously shown to improve photoreceptor structure and function.

We confirmed in both groups of animals that CNTF reduces the loss of photoreceptor cells.

Visual function, however, as assessed over a time course by electroretinography (ERG), was significantly reduced compared with untreated controls. Furthermore, CNTF gene expression negated the effects on function of gene replacement therapy.

In order to test whether this deleterious effect is only seen when degenerating retina is treated, we recorded ERGs from wild-type mice following intraocular injection of AAV expressing CNTF. Here a marked deleterious effect was noted, in which the b-wave amplitude was reduced by at least 50%.

Our results demonstrate that intraocular CNTF gene delivery may have a deleterious effect on the retina and caution against its application in clinical trials.

Go to ...

Top of Page.

Previous Page.

List of Categories.

Home Page.

Blind World Website
Designed and Maintained by:
George Cassell
All Rights Reserved.

Copyright Notice
and Disclaimer.