Electronic Implants To Treat Blindness Clinical Trial Restores Unprecedented Level Of Vision

Retina Implant, AG, a leading developer of electronic implants to treat blindness, today announced successful results from the company’s first human clinical trial. The company is now setting up a UK trial of the implant. The results achieved in the 11 patients involved in the preliminary study far exceeded the company’s expectations. In fact, some patients were able to see objects and shapes clearly enough to read large letters and recognize words. Although other companies have developed retinal implants, until now the technology facilitated the ability to see light and outlines of objects, but did not produce a level of sight that enabled patients to read. Retina Implant’s clinical trial began in Germany in 2005 and has involved 11 patients who lost their sight due to retinitis pigmentosa (RP). The UK clinical trial will be led by Professor Robert MacLaren, Professor of Ophthalmology at the University of Oxford and a consultant retinal surgeon at the Oxford Eye Hospital and includes Mr Tim Jackson, a consultant retinal surgeon at King’s College Hospital in London.

There are two main approaches to retinal implants currently being developed by scientists across the globe: epiretinal and subretinal. Both electronic implants stimulate the retina, which is a light sensitive sheet of nerve cells at the back of the eye, similar to the film of a camera. In diseases such as RP and macular degeneration, the retina itself degenerates and loses its light sensitivity, rendering affected patients blind. The ‘epiretinal’ approach involves sticking an electronic implant in front of the retina to stimulate the nerve cells. The surgery to do this is more straightforward, but the epiretinal implant is not itself light sensitive and needs to be connected to a camera outside the eye, often mounted on the patient’s spectacles. The new ‘subretinal’ approach developed by Retina Implant AG involves placing the electronic device underneath the retina, which is technically challenging but stimulates the nerve cells in a more natural position. This may explain the dramatic visual results revealed by the company today. Furthermore the subretinal device is itself light sensitive, with a 1500 pixel array. This is stimulated by the natural image focused by the eye which completely does away with the need for an external camera.

“I have been working in developing new treatments for patients with retinal diseases for many years and I was initially skeptical about the role of electronic devices. However, this recent work by the Retina Implant team is very impressive indeed and I would now certainly consider this technology as a viable treatment option for patients blind from RP,” says Professor MacLaren. “It’s much more logical to place the implant underneath the retina where the residual neurons are orientated towards the implant electrodes, because this should equate to a much higher pixel resolution. Another development is that the implant itself is light sensitive, which I would view as a major technological advance because the whole device can be contained within the eye. A power supply is fed through a battery behind the ear similar to a hearing aid. This represents a true fusion of an electronic interface with the human central nervous system and we are likely now to learn a lot more about this technology as the trial progresses.”

Retinitis pigmentosa (RP) is one of the most common forms of inherited retinal degenerations affecting approximately 200,000 people in the world. A progressive condition that gets worse over time, RP typically causes severe vision problems in adulthood. While there are currently no approved treatment options that can restore vision for RP patients or impede the progression of the disease, retinal implants represent tremendous promise for enabling RP patients to regain sight.

“During the course of our first trial, we learned a great deal between our first and last patient, especially from patient 10 to 11,” said Dr. Walter-G. Wrobel, president and CEO of Retina Implant, AG. “Paramount in this discovery was learning that using the subretinal approach to place the chip in the macular region provided superior clinical outcomes. The eleventh/last patient in the study was the only one to have the chip placed exactly in the macular region, and he was able to see more clearly than any other patient in the trial. Additionally, every patient tolerated the surgery well; no adverse events occurred.”

“I first noticed my eyesight was impaired at 16, and over a period of 16-17 years, my condition deteriorated to complete blindness,” said the 11th patient, a 45 year-old Finland-based male. “I knew there was a chance the implant wouldn’t enable me to see anything, but I was willing to participate in the research with the hope I would regain some sight. When the microchip was turned on, I immediately was able to distinguish light from dark and see outlines of objects. As I got used to the implant, my vision improved dramatically. I was able to form letters into words, even correcting the spelling of my name. I recognized foreign objects such as a banana and could distinguish between a fork, knife and spoon. Most impressively, I could recognize the outlines of people and differentiate heights and arm movements from 20 feet away.”

Retina Implant is presenting results of this clinical trial at the Association for Research in Vision and Ophthalmology’s (ARVO) annual meeting May 2 – 6 in Fort Lauderdale, Fla.

Retina Implant, AG

Study: Lower Macular Degeneration Risk In Postmenopausal Women Taking Hormones

A study published in the Archives of Ophthalmology reports
that there is an association between women who take postmenopausal
hormones and the risk of developing age-related macular degeneration.
Diane Feskanich, Sc.D., (Brigham and Women’s Hospital and Harvard
Medical School, Boston) and colleagues found that, especially for women
who had taken oral contraceptives, postmenopausal hormones
reduced the risk of progressing to advanced stages of the eye disease.

Among older adults, age-related macular degeneration (AMD) is the chief
cause of blindness and loss of vision. The condition is responsible for
profound vision loss in 1.75 million
“Although genetics plays a key role in susceptibility to AMD,
environmental factors, such as smoking, are also important,” write
Feskanich and colleagues. “Evidence of higher rates of AMD in women
than in men
and links between AMD and cardiovascular disease suggested a role for
estrogen,” in how the disease develops.

The researchers used data from the Nurses’ Health Study to analyze AMD
and factors related to estrogen such as postmenopausal
hormone use, oral contraceptive use, ages of menarche (first period)
menopause, and history of childbirth. Of the 74,996 post-menopausal
women in the sample, 554 and 334 developed beginning-stage and
neovascular AMD, respectively, between 1980 and 2002. The neovascular
stage of AMD is more advanced and results in the development of new
blood vessels.

The researchers found that, “Current postmenopausal hormone users had a
notable 48 percent lower
risk of neovascular AMD compared with those who had never used
postmenopausal hormones, although risk did not decline linearly with
longer durations of use. Risk was lowest for
postmenopausal hormone users who had used oral contraceptives in the

However, oral contraceptive use was not linked to early AMD risk, and
current postmenopausal hormone users were 34% more likely to develop
early stage AMD than non-users. “The higher risk of early AMD among
postmenopausal hormone users was unexpected and in apparent conflict
with the observed inverse association for neovascular AMD,” write the

In addition, researchers found a 26% lower risk of early AMD among
women who had given birth.

The authors conclude that, “Taken together, these findings suggest a
role for estrogen in the
pathogenesis of AMD that requires further research in specific early
and late signs of disease.”

Menopausal and Reproductive Factors and Risk of Age-Related
Macular Degeneration
Diane Feskanich, ScD; Eunyoung Cho, ScD; Debra A. Schaumberg, ScD, OD,
MPH; Graham A. Colditz, MD, DrPH; Susan E. Hankinson, ScD
Archives of Ophthalmology (2008). 126[4]:
Here to View Abstract

: Peter M Crosta

New Finding In Rare Eye Disease

Researchers have made a finding which could pave the way for new treatments for sufferers of a rare eye disease which can lead to blindness.

In a paper published in the Journal of Pathology, scientists reveal they have discovered why mutations in a key gene can cause the cornea to go opaque and lead to sight loss.

Pax6 is the gene responsible for the development of the eye and mutations of it can cause the cornea to go cloudy.

Corneas – our windows on the world – are delicate, transparent tissues which are constantly exposed to potentially damaging environmental factors such as daylight, ultraviolet light and high levels of oxygen.

Normal corneas contain proteins that protect against the day to day stress of coping with these environmental stresses.

But around one in 40,000 people have Pax6 mutations which lead to them developing a condition called Aniridia, where the iris of the eye is missing.

As well as having no iris, most sufferers will develop some degree of corneal cloudyness which is called Aniridia-Related Keratopathy or ARK.

Now researchers have found that people with ARK have tiny holes in their corneas, which open up the corneas to extra levels of stress. They also discovered that they have less of the protective proteins, which results in their eyes being unable to cope with everyday conditions. Over time, this leads to the corneas going cloudy.

Dr Martin Collinson, a Senior Lecturer in Biomedical Sciences at the University of Aberdeen, led the research team. He said: “In the worst cases Aniridia-Related Keratopathy can be chronically painful and sight threatening. Current therapy is surgery, anti-inflammatory drugs, or nothing at all.”

The researchers found that if they applied chemicals to diseased corneas, they were able to reduce the stress caused by oxygen. This in turn gave cells on the eye’s surface more of a fighting chance of protecting the eye.

Dr Collinson added: “Our findings provide answers to a disease that has been very poorly understood and is rather difficult to treat.

“We hope that our studies could potentially lead to new treatments for people with ARK that could involve eye drops as opposed to surgery.”

The studies were undertaken during research funded by the Birth Defects Foundation charity Newlife and the BBSRC – Biotechnology and Biological Sciences Research Council.

University of Aberdeen

Lucentis(R) (Ranibizumab) Launched For Vision Loss Due To Diabetic Macular Oedema, A Serious And Common Complication Of Diabetes

Novartis Pharmaceuticals UK Ltd announced that Lucentis® (ranibizumab) has launched in the UK for the treatment of visual impairment due to diabetes, specifically diabetic macular oedema (DMO). This offers fresh hope for people with this serious and common complication of diabetes. Until now, laser treatment has been the current standard treatment but has not been shown to improve vision. Ranibizumab not only offers stabilisation of vision loss but can also lead to significant improvements in vision. It is the first licensed therapy to improve vision and vision-related quality of life in people with visual impairment due to diabetic macular oedema.3

Approval for this new indication for ranibizumab was based on data from two pivotal randomised Phase III trials, which demonstrated ranibizumab provided rapid, superior and sustained vision gains compared to the current standard of treatment.3,4 Data from the RESTORE Phase III study (354 eyes), show that ranibizumab is significantly more effective at treating visual impairment due to DMO, compared to laser treatment.3 At one year, the RESTORE results show that on average 37% of people treated with ranibizumab 0.5 mg alone, and 43% of those treated with ranibizumab plus laser therapy, gained a substantial vision improvement of 10 letters or more on an eye-chart, versus 16% of people treated with laser alone.3 In addition, ranibizumab was shown in the RESTORE Phase III study to provide a significant improvement in quality of life.3

The safety profile of ranibizumab in RESTORE is consistent with that previously observed in large controlled clinical trials for wet age-related macular degeneration (wet AMD), with no new safety risks observed. These efficacy and safety data support the earlier results of the pivotal RESOLVE study comparing ranibizumab to sham treatment.4

Mr. Nicholas Beare, Consultant Ophthalmologist, Royal Liverpool University Hospital, UK investigator in the RESTORE trial, explains what this new option means for the future of treating this condition “It is great news for both clinicians and people with diabetes alike that ranibizumab is now available to treat DMO in the UK. Ranibizumab has the potential to transform the way we treat DMO in the UK. For the last 25 years, laser therapy has been the standard of care in DMO but it is not generally associated with visual improvement, whereas ranibizumab has been shown to produce a rapid and sustained improvement in vision.”

DMO affects 5-10% of people with diabetes, and in many it will cause visual impairment.5 Visual loss due to DMO occurs in around 50,000 people in the UK.6,7 For people with diabetes, visual impairment is one of the most feared complications of the condition8 and is most often caused by DMO. People with visual impairment due to DMO are less able to live and work independently.

If DMO is left untreated, there is a 25-30% risk of developing clinically significant macular oedema, leading to vision loss.8 Moderate visual loss will occur in approximately 24% of untreated eyes where clinically significant macular oedema has developed.8 Furthermore, even with current treatment, 12% of eyes develop moderate visual loss after 3 years.1

Ranibizumab is currently licensed and marketed for wet AMD in more than 8010 countries, and it benefits from continuous safety monitoring through systematic pharmacovigilance.

The safety profile of ranibizumab in DMO is comparable to that seen in previous studies for Age-related Macular Degeneration (AMD), adding further weight to its established safety profile, shown through the robust ranibizumab clinical trial programme.11, 12, 13

About ranibizumab

Ranibizumab has been approved in the UK and more than 8010 countries for the intraocular treatment of wet age-related macular degeneration (AMD) under the brand name Lucentis®. Ranibizumab is the only NICE approved treatment for wet AMD and received EMA approval for the treatment of DMO with visual impairment on January 07, 2011. Ranibizumab was developed by Genentech and Novartis. Genentech has the commercial rights in the US, while Novartis has exclusive rights in the rest of the world.

About DMO

Diabetic macular oedema (DMO) is a consequence of diabetic retinopathy, the most common diabetic eye complication, and is characterised by changes in the blood vessels of the retina, the light-sensitive layer at the back of the eye. In people with DMO, leakage from these abnormal blood vessels occurs in the central portion of the retina, called the macula. Because this part of the eye is responsible for sharp central vision, DMO can lead to significant visual impairment. DMO affects 5-10%,5 and with visual impairment approximately 1-3%14 of people with diabetes,6,7 and DMO is a leading cause of blindness in the working-age population in most developed countries.



1. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol. 1985 Dec;103 (12):1796-806.

2. Cuilla TA et al. Diabetes Care 2003; 26:2653-2664

3. Data on file. Novartis Pharmaceuticals UK Ltd. LUCDOF10 -008 – RESTORE 12 month data

4. Data on file. Novartis Pharmaceuticals UK Ltd. LUCDOF-007- RESOLVE study

5. Chen et al 2010 Curr Med Res Opin 2010; 26: 1587-97

6. Data on file. Novartis Pharmaceuticals UK Ltd. Advanced notification and planning information for NHS decision makers and policy holders, July 2009: ranibizumab (Ranibizumab)

7. Diabetes UK. Diabetes in the UK 2010: Key statistics on diabetes 2010

8. Davidov E et al. Graefes Arch Clin Exp Ophthalmol 2009;247:267-272

9. National Institute for Health and Clinical Excellence. Draft scope for the proposed appraisal of ranibizumab for the treatment of diabetic macular oedema, 2010.

10. Data on file. Novartis Pharmaceuticals UK Ltd LUCDOF10-014

11. Rosenfeld PJ et al. N Engl J Med 2006;355:1419-1431

12. Brown DM et al. Ophthalmology 2009;116:57-65

13. Regillo CD et al. Am J Ophthalmol 2008;145:239-248

14. Data on file. Novartis Pharmaceuticals UK Ltd. LUCDOF10-009



View drug information on Lucentis.

Lux Biosciences Files For LUVENIQ™ Approval In US And Europe For Noninfectious Uveitis

Lux Biosciences, Inc. today announced its submission of simultaneous regulatory filings to both the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) seeking marketing approval for its investigational drug LUVENIQ™ (LX211; oral voclosporin) for the treatment of noninfectious uveitis involving the intermediate or posterior segments of the eye. Efficacy of LX211 in support of the indication sought was demonstrated in two controlled, randomized, multi-center trials including data from 450 patients at 56 sites in 7 countries. The safety data include a total of 2,110 subjects who received voclosporin during its clinical development in uveitis and psoriasis, about 500 of whom were treated for >36 weeks and about 200 for >52 weeks. LX211 had previously received orphan drug status from FDA and EMA, and fast track status from FDA. Based on the latter, Lux Biosciences has requested priority review from FDA.

“The results seen in the LUMINATE clinical trial program, the largest completed to date in non-infectious uveitis, support our belief that LX211 has the potential to significantly advance the treatment of this blinding disease,” said Ulrich Grau, Ph.D., Lux Biosciences’ President and Chief Executive Officer. “This is the first regulatory filing of voclosporin in any indication, in any country, which made this submission a complex task. It incorporates the research and development undertaken by our collaboration partner Isotechnika over more than a decade, and that of Lux Biosciences over the last 3 ?? years. Simultaneous filings of both a U.S. New Drug Application (NDA) and a European Marketing Authorization Application (MAA) for LX211 represent a major milestone for Lux Biosciences.”

He added, “I wish to thank all of the Lux Biosciences employees, our partner Isotechnika, investigators, patients, contractors and advisors who contributed to the development program and made these on-time filings possible. I am not aware of a company of our small size having accomplished a submission of this magnitude for a new molecular entity simultaneously in the United States and Europe. It is a tribute to our networked approach to development, whereby a large team led and managed by a small core group was able to complete a major international drug development program in record time.”

Results from the LUMINATE program, submitted in support of both the U.S. and European marketing applications, showed that LX211 at the recommended dose of 0.4 mg/kg twice daily provided clinically meaningful efficacy and enabled preservation of vision in treated patients, a critical patient benefit. Study LX211-01, in subjects with uncontrolled uveitis, showed LX211 to rapidly reduce inflammation in subjects with moderately severe disease, either alone or in combination with systemic corticosteroids. Subjects receiving LX211 experienced a 50% reduction in mean vitreous haze as compared to 29% in placebo-treated subjects. The proportion of subjects demonstrating an improvement of at least 2 grades in vitreous haze or a grade of ?��1+ for the study eye at last visit was 64% in the LX211 group as compared to 46% in the placebo group. Moreover, treatment with LX211 permitted the withdrawal of immunosuppressive therapy and the use of 5 mg/day or less of prednisone.

Study LX211-02 demonstrated the efficacy of LX211 in subjects whose disease was clinically quiescent at the time of enrollment. Nearly 90% of the patients in this study were receiving one or more forms of systemic immunosuppression prior to randomization. In this study, treatment with LX211 resulted in a 50% reduction in the rate of inflammatory exacerbations at the 26-week primary endpoint compared to those receiving placebo; a similar result was observed at 50 weeks. This indicates that relative to placebo, a patient’s exposure to ocular inflammatory exacerbations that lead to loss of vision and to potentially damaging exposure to high rescue doses of steroids is approximately cut in half when LX211 therapy is administered at the clinically effective dose. Treatment with LX211 also enabled the concomitant withdrawal of immunosuppressive therapy and allowed the reduction of systemic corticosteroids to 5 mg/day or less, as well as the complete elimination of topical corticosteroid therapy.

The most common adverse events (>5%) occurring at a rate higher in treated patients than those receiving placebo, regardless of whether they were drug related or not, were hypertension, decreased renal function, diarrhea, pyrexia and arthralgia. All cases of reported hypertension were treatable, and all cases of decreased renal function were reversible. The most commonly observed infections reported were nasopharyngitis, urinary tract infection, and upper respiratory infections, but no opportunistic infections were observed. Adverse event risks in general did not appear to be increased with longer-term use. Additionally, no meaningful signals of more serious treatment effects were observed, even at a lesser frequency, in either study.

“LX211 at the recommended dose of 0.4 mg/kg twice daily, possesses a favorable benefit-risk profile for the treatment of noninfectious uveitis involving the intermediate or posterior segments of the eye,” said Eddy Anglade, M.D., Lux Biosciences Chief Medical Officer. “If approved, LX211 would offer physicians a valuable oral treatment option capable of modifying the course of uveitis by effectively controlling the inflammation that characterizes this potentially blinding eye disease and significantly reducing its rate of recurrence. Avoiding inflammatory exacerbations that result in ocular morbidity and the loss of vision, coupled with avoidance of steroid-induced morbidities, is central to the management of patients afflicted with uveitis. LX211 has been shown to provide a means to attain these therapeutic goals in a disease that requires effective intervention and for which current therapeutic options are limited and deficient.”


LUVENIQ (LX211) is the oral form of a next-generation calcineurin inhibitor, voclosporin. Like other molecules of this class, the compound reversibly inhibits immunocompetent lymphocytes, particularly T-lymphocytes, and it also inhibits lymphokine production and release. Lux Biosciences has exclusive worldwide rights to voclosporin for ophthalmic use and is cooperating with the team at Isotechnika Pharma who discovered the molecule and develop it in psoriasis and organ transplantation.

About Uveitis

Uveitis, which represents a group of serious inflammatory eye conditions, is inevitably associated with either severe vision loss or substantial morbidity from steroid use. Non-infectious uveitis involving the posterior segment of the eye is a leading cause of vision loss and long-term disability and the fourth leading cause of legal blindness in the industrialized world. As the majority of uveitis patients are first diagnosed at ages under 40 years, the socio-economic burden of this disease is higher than that of other serious ocular conditions such as AMD and diabetic macular edema.

Lux Biosciences

How Deaf People’s Brains Change To Boost Sight

After studying the brains of congenitally deaf cats, the only animal apart from humans that can be born deaf, researchers
proposed that the part of the brain normally used for hearing is reorganized to boost sight in deaf people, thus explaining their
reported capacity for “supersight”.

You can read how the researchers made their discovery in a paper that was published online in the journal Nature
Neuroscience on 10 October.

The lead author was Dr Stephen G Lomber of The Centre for Brain and Mind at The University of Ontario in Canada, and his
co-authors were Dr M Alex Meredith of the School of Medicine at Virginia Commonwealth University in the US and Dr Andrej
Kral of Hannover Medical University’s Institute of Audioneurotechnology in Germany.

When the brain doesn’t receive input from one sense that is not working, it often compensates by boosting performance of another
sense that is working: for example deaf and blind people often report enhanced ability in other senses. But what remains a bit of
a mystery is how this happens neurologically.

As a result of what they found in congenitally deaf cats, Lomber and colleagues proposed that the brain is “plastic” enough to
reallocate areas normally dedicated to one sense to further the performance of the remainder.

Lomber, who is an associate professor in the Department of Physiology and Pharmacology at the Schulich School of Medicine &
Dentistry, and Department of Psychology in the Faculty of Social Science, both at The University of Ontario, explained that the
brains of deaf people probably use the redundant auditory brain areas to boost visual performance in two ways: enhancing
peripheral vision and detecting how fast things around them are moving.

For example, he said, ” if you’re deaf, you would benefit by seeing a car coming far off in your peripheral vision, because you
can’t hear that car approaching from the side; the same with being able to more accurately detect how fast something is

“The brain wants to compensate for the lost sense with enhancements that are beneficial,” said Lomber, adding that the “brain is
very efficient, and doesn’t let unused space go to waste”.

He and his colleagues already had a hunch that this was the case: “it has been proposed that cross-modal reorganization of deaf
auditory cortex may provide the neural substrate mediating compensatory visual function,” they wrote, so they tested their
hypothesis comparing congenitally deaf cats to hearing cats while they performed a series of psychophysically challenging

They found that the deaf cats had “have superior localization in the peripheral field and lower visual movement detection
thresholds”, compared to the hearing cats.

But when they performed reversible brain operations in the deaf cats that deactivated the posterior auditory cortex (the part that
normally picks up peripheral sound), they found the cats lost their superior performance in peripheral vision, which led them to
suggest the function stayed the same (to detect peripheral signals), but just switched from auditory to visual.

They also found that deactivating the deaf cats’ dorsal auditory cortex made them lose their superior visual motion

So Lomber and colleagues concluded that:

“Our results indicate that enhanced visual performance in the deaf is caused by cross-modal reorganization of deaf auditory
cortex and it is possible to localize individual visual functions in discrete portions of reorganized auditory cortex.”

Lomber and colleagues now want to investigate further how this phenomenon might affect deaf people who get cochlear
implants. What happens to the brains of people who have been deaf all their lives when they suddenly start getting auditory signals
to process; especially if the areas normally used to process hearing are being used to boost sight?

Lomber drew an analogy with letting a friend settle into a cottage you weren’t using for a while. And then suddenly you find you
need it back: but they have made themselves comfortable, rearranged the furniture, and made it suit their needs.

“They may not want to leave just because you’ve come back,” explained Lomber.

The team are also hoping to investigate if these same changes happen in the brains of people were not deaf at birth but became
deaf later in life. They want to know, for example, if experience of hearing stops the brain reorganizing the auditory cortex to
boost another sense.

“Cross-modal plasticity in specific auditory cortices underlies visual compensations in the deaf.”
Stephen G Lomber, M Alex Meredith & Andrej Kral.
Nature Neuroscience, Published online: 10 October 2010.

Source: University of Western Ontario.

: Catharine Paddock, PhD

Inspire Completes Patient Enrollment In Three Late-Stage Clinical Trials In Cystic Fibrosis, Dry Eye And Blepharitis

Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) announced today patient enrollment is complete in three of its late-stage clinical trials.

“We are pleased to be executing on our strategic plan with the achievement of these patient enrollment milestones in the clinical development programs for denufosol, PROLACRIA™ and AZASITE®, as this places us in a position to have top-line results from all our late-stage clinical programs within 18 months. We would like to thank the dedicated clinical investigators, study coordinators and patients who participated in our trials as well as the Cystic Fibrosis Foundation and its affiliates for raising awareness of the importance of participating in clinical trials,” stated Benjamin R. Yerxa, Ph.D., Executive Vice President and Chief, Research and Development.

Denufosol Tetrasodium for Cystic Fibrosis

Inspire announced today that TIGER-2, the Company’s second Phase 3 pivotal clinical trial (Trial 08-110) with denufosol tetrasodium inhalation solution for the treatment of cystic fibrosis (CF), has completed patient enrollment. TIGER-2 is a 48-week trial comparing 60 mg of denufosol to placebo, administered three-times daily by jet nebulizer, in a targeted 450 CF patients. The Company expects to have top-line results from TIGER-2 in the first quarter of 2011.

“We are excited that patient enrollment in TIGER-2 is complete. This is an important step toward bringing this potential new treatment to cystic fibrosis patients,” said Robert J. Beall, Ph.D., President and CEO of the Cystic Fibrosis Foundation. “Denufosol’s novel approach to treating the underlying ion channel defect in CF lung disease makes it a promising therapy, and we look forward to the results from this trial.”

PROLACRIA™ for Dry Eye

Inspire also announced today that patient enrollment is complete in its Phase 3 clinical trial (Trial 03-113) with PROLACRIA, the proposed U.S. tradename for diquafosol tetrasodium ophthalmic solution 2%, for the treatment of dry eye disease. This is a six-week trial comparing PROLACRIA to placebo, administered four-times daily as eye drops, in a targeted 450 dry eye patients. The trial is based on a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA). The Company expects to have top-line results from this trial in the first quarter of 2010.

Gary N. Foulks, M.D., F.A.C.S., Professor of Ophthalmology and Visual Science and Director of Corneal/External Disease at Kentucky Lions Eye Center, University of Louisville, and principal investigator of Trial 03-113, stated, “There is a significant need for new therapeutic treatments for dry eye disease. With its novel mechanism of action of stimulating the production of natural tear components, PROLACRIA could be of significant benefit to patients suffering from dry eye.”

AZASITE® for Blepharitis

The AZASITE (azithromycin ophthalmic solution) 1% for blepharitis Phase 2 program is targeted to enroll approximately 600 patients in two trials. One trial (Trial 044-101) includes a two-week treatment period with a two-week follow-up period and the other trial (Trial 044-102) includes a four-week treatment period with a four-week follow-up period. Inspire announced today that enrollment is complete in the four-week trial and enrollment in the two-week trial is progressing well with 250 out of a targeted 300 patients enrolled. The Company expects to have enrollment completed in the two-week trial in the first quarter of 2010.

About Denufosol Tetrasodium

Denufosol tetrasodium is a first-in-class receptor-mediated chloride channel activator that addresses the underlying ion transport defect in the lungs of patients with cystic fibrosis (CF). Denufosol is designed to enhance airway hydration and mucociliary clearance through receptor-mediated mechanisms that increase chloride secretion, inhibit sodium absorption and increase ciliary beat frequency. These integrated pharmacological actions are important to restoring airway clearance, maintaining lung function, and potentially delaying the progression of CF lung disease. Denufosol is targeted as an early intervention therapy for CF lung disease. This product candidate has been granted orphan drug and fast-track review status by the U.S. Food and Drug Administration (FDA) and orphan drug status by the European Medicines Agency (EMEA).


PROLACRIA, the proposed U.S. tradename for diquafosol tetrasodium ophthalmic solution 2%, is a proprietary and selective P2Y2 agonist Inspire is developing for the treatment of dry eye disease. PROLACRIA is designed to stimulate the release of the three natural tear components involved in tear secretion – mucin, lipids and fluid.


AZASITE (azithromycin ophthalmic solution) 1% is a prescription medicine approved by the U.S. Food and Drug Administration for the treatment of bacterial conjunctivitis in adults and children 1 year of age and older. AZASITE is for topical ophthalmic use only. In clinical trials, the most frequently reported ocular adverse event was eye irritation, which occurred in 1% – 2% of patients. Please see full Prescribing Information for AZASITE at azasite. Inspire is pursuing an additional potential indication for AZASITE for the treatment of blepharitis.


View drug information on AzaSite.

New Mechanism For Circadian Rhythm Discovered By Texas A&M Researchers

Molecules that may hold the key to new ways to fight cancer and other diseases have been found to play an important role in regulating circadian rhythm, says Liheng Shi, a researcher in Texas A&M’s Department of Veterinary Integrative Biosciences.

Circadian rhythm is the roughly 24-hour cycle of physiological activities of humans, animals and even bacteria, Shi explains.

He and colleagues have had their research, currently focusing on the circadian rhythm in chickens’ eyes, published in the Journal of Biological Chemistry. Chicken eyes have a lot in common with human eyes.

“The prefix ‘photo-‘ in photoreceptors means light, and photoreceptors in animals’ eyes receive light signals and then translate them into signals that their brain can understand, and that is how they see,” he explains.

Shi notes there are two kinds of photoreceptors – cone photoreceptors and rod photoreceptors, named for the shape they resemble.

Some channels that scientists call L-VGCCs are important to the circadian rhythm in chickens’ eyes. These channels are important because they are the pathways through which messages go in and out of photoreceptors, and these messages are crucial to the proper functioning of the eye.

A group of proteins (L-VGCC?�1C) carries the messages in and out. At night, they get more work done than during the day to “prepare chickens’ eyes for another day’s busy work” and “tell various parts of the eye to adjust to the darkness,” explains Shi, who holds a post-doctoral position under the mentorship of Gladys Ko, one of the coauthors of the article.

These proteins are controlled by messengers called mRNA, and they are especially active, raising the question of why, he says.

“There must be an explanation,” Shi says, “and we found a possible answer.”

The answer lies in a sibling of the messenger named microRNA-26a, a “small guy” in the RNA family.

“During the day, the ‘naughty small guy’ crawls onto the back of his brother mRNA, so his brother cannot concentrate on his work,” the Texas A&M researcher explains. “At night, however, he lets his brother go, so his brother focuses on his work and gets more work done.”

He advises not to “look down” on the mRNA. “If they quit their job, the chicken may become blind,” Shi adds. “Besides regulating circadian rhythm, the microRNA family also influence cancer development, cell division, heart disease, and so on.”

“What we know about microRNAs is probably only a tip of the iceberg,” the Texas A&M postdoc says. “As we get to know more about them, these small guys may be able to help us diagnose and treat many diseases.”

Liheng Shi

Texas A&M University

Research Highlights From The AAO-SOE Joint Meeting

The 2008 Joint Meeting of the American Academy of Ophthalmology (Academy) and European Society of Ophthalmology (SOE ), the largest and most comprehensive ophthalmic educational meeting in the world, is in session November 8 to 11 at the Georgia World Congress Center, Atlanta. Offerings include 277 continuing medical education courses, 179 “Breakfast with the Experts” roundtables, 95 skills transfer courses, and more than 100 hours of scientific presentations, at no charge.

The scientific program includes reports on a potential biomarker for age-related macular degeneration (AMD) that may also imply common biological signaling mechanisms for general aging and AMD, and on positive results in keratoconus patients treated with a promising technique, corneal collagen crosslinking.

Plasma Interleukin 6 as a Potential Biomarker of Age-related Macular Degeneration (AMD)

In its advanced stages, AMD destroys the detailed, central vision we need to read, drive, recognize faces, and enjoy daily life, and is a major cause of vision loss in the U.S. Ophthalmic researchers are making rapid progress in understanding how genetics, immune system factors, nutrition choices, and other variables interact to produce or prevent AMD. These discoveries will enable ophthalmologists (Eye M.D.s) to more precisely identify those who are likely to develop AMD, to select optimal, individualized treatments, and to monitor the disease.

Janice C. Law, MD, and her colleagues at the Vanderbilt Eye Institute, looked for plasma (blood) biochemical markers, or biomarkers, that would indicate systemic oxidative stress and an inflammatory response in 57 patients with AMD and in an age-matched control group. Oxidative stress occurs in the body when there is an imbalance between cells’ production of reactive oxygen (such as superoxide and hydrogen peroxide) and cells’ ability to detoxify byproducts of reactive oxygen, such as free radicals, which can damage protein, DNA and other cell components. In an inflammatory response, the body’s vascular and immune systems work in concert to remove disease-causing agents, damaged cells, or other irritants, and to initiate tissue healing. If immune system regulation goes awry, an overly strong inflammatory response–such as hay fever or atherosclerosis–can result.

In Dr. Law’s study an inflammation-promoting biochemical, interleukin 6 (IL-6), was found to be significantly higher in the AMD patients, and IL-6 levels also correlated with oxidative stress measurements in these patients. This suggests that IL-6 is a good candidate for further study as a potential AMD biomarker. It also indicates that common biological signaling mechanisms may be involved in both oxidative stress and inflammation and may contribute to AMD development as well as general aging.

Other recent research has established that AMD is closely associated with certain genetic variations that control aspects of the immune system, especially the inflammatory response. Numerous studies have also confirmed the role of oxidative stress in AMD development and progression. Dr. Law’s study focused on plasma-based biomarkers because blood sample screening is a relatively simple yet accurate diagnostic tool.

This preliminary cohort study did not attempt to determine whether IL-6 levels varied with AMD types–“wet” AMD, characterized by rapid growth of abnormal blood vessels and heightened risk of vision loss, or the more common “dry” type–or with disease severity.

Corneal Collagen Crosslinking: Treatment Results in Keratoconus Patients

Keratoconus is an eye disorder that causes corneal tissue to become abnormally thin and the central area to protrude in a cone shape, distorting vision. The cornea is the clear tissue that covers the front of the eye and is crucial to focusing light on the back of the eye. In the US, keratoconus occurs in 50 to200 per 100,000 people; reported rates vary with the criteria used for diagnosis. Unofficial reports indicate this disorder may be more prevalent in the Indian subcontinent, Arabia, and New Zealand. Although usually a progressive disease, recent data suggests that it stabilizes after time in most patients, and that treatment with rigid contact lenses is successful for many. Ten to 20 percent of keratoconus patients in the US eventually receive corneal transplants to restore their vision.

Co-investigators Mohan Rajan, MD, and Sujatha Mohan, MD, of the Rajan Eye Care Hospital, India, studied collagen crosslinking in 48 patients (60 eyes), aged 12 to 48 years, who had progressive keratoconus. The collagen crosslinking technique, developed in recent years, is under study for the treatment of several eye disorders. In keratoconus patients, drops containing riboflavin, a B-complex vitamin, are applied to the cornea which is then exposed to UVA light; this stimulates collagen fibers to connect to one another, or crosslink. Collagen is the primary protein constituent of the body’s connective tissues. The procedure helps restore appropriate curvature and structure to the cornea, and makes it possible for most patients who need them to wear rigid contact lenses again. Collagen crosslinking may prove a viable alternative to cornea transplant, and three FDA-approved trials are now underway in the US.

The Rajan-Mohan study involved 40 eyes (group A) in which infected tissue and any foreign matter were removed from the top tissue layer, and 20 eyes (group B) in which the tissue layer was left intact prior to treatment. Patients received follow-up exams at one, three, six and twelve months. Vision corrected with eyeglasses or contact lenses improved in 45 percent of patients by six months, but no change was noted in any patients’ vision when measured without eyeglasses or contact lenses. The corneal curve flattened appropriately in 51 of 60 eyes (85 percent), with more significant flattening in group A patients. Based on subjective reports, 46.6 percent of participants were better able to tolerate wearing contact lenses. No significant side effects were noted.

“In our study collagen crosslinking showed promising results,” said Dr. Mohan. “The positive corneal changes observed in these patients, together with improved vision and contact lens tolerance, indicates that it was a safe and effective procedure for these keratoconus patients.” Because it is less invasive than corneal transplant, the patient’s surgery-related risks are reduced. As a less expensive, technically simpler procedure, collagen crosslinking could be particularly useful in developing countries where corneal transplant and other procedures may be difficult to access.

About the American Academy of Ophthalmology

AAO is the world’s largest association of eye physicians and surgeons – Eye M.D.s – with more than 27,000 members worldwide. Eye health care is provided by the three “O’s” – opticians, optometrists and ophthalmologists. It is the ophthalmologist, or Eye M.D., who can treat it all: eye diseases and injuries, and perform eye surgery. To find an Eye M.D. in your area, visit the Academy’s Web site at aao/

Source: Mary Wade

American Academy of Ophthalmology

Stem Cell Therapy Makes Cloudy Corneas Clear, According To Pitt Researchers

Stem cells collected from human corneas restore transparency and don’t trigger a rejection response when injected into eyes that are scarred and hazy, according to experiments conducted in mice by researchers at the University of Pittsburgh School of Medicine. Their study will be published in the journal Stem Cells and appears online today.

The findings suggest that cell-based therapies might be an effective way to treat human corneal blindness and vision impairment due to the scarring that occurs after infection, trauma and other common eye problems, said senior investigator James L. Funderburgh, Ph.D., associate professor, Department of Ophthalmology. The Pitt corneal stem cells were able to remodel scar-like tissue back to normal.

“Our experiments indicate that after stem cell treatment, mouse eyes that initially had corneal defects looked no different than mouse eyes that had never been damaged,” Dr. Funderburgh said.

The ability to grow millions of the cells in the lab could make it possible to create an off-the-shelf product, which would be especially useful in countries that have limited medical and surgical resources but a great burden of eye disease due to infections and trauma.

“Corneal scars are permanent, so the best available solution is corneal transplant,” Dr. Funderburgh said. “Transplants have a high success rate, but they don’t last forever. The current popularity of LASIK corrective eye surgery is expected to substantially reduce the availability of donor tissue because the procedure alters the cornea in a way that makes it unsuitable for transplantation.”

A few years ago, Dr. Funderburgh and other University of Pittsburgh researchers identified stem cells in a layer of the cornea called the stroma, and they recently showed that even after many rounds of expansion in the lab, these cells continued to produce the biochemical components, or matrix, of the cornea. One such protein is called lumican, which plays a critical role in giving the cornea the correct structure to make it transparent.

Mice that lack the ability to produce lumican develop opaque areas of their corneas comparable to the scar tissue that human eyes form in response to trauma and inflammation, Dr. Funderburgh said. But three months after the lumican-deficient mouse eyes were injected with human adult corneal stem cells, transparency was restored.

The cornea and its stromal stem cells themselves appear to be “immune privileged,” meaning they don’t trigger a significant immune response even when transplanted across species, as in the Pitt experiments.

“Several kinds of experiments indicated that the human cells were alive and making lumican, and that the tissue had rebuilt properly,” Dr. Funderburgh noted.

In the next steps, the researchers intend to use the stem cells to treat lab animals that have corneal scars to see if they, too, can be repaired with stem cells. Under the auspices of UPMC Eye Center’s recently established Center for Vision Restoration, they plan also to develop the necessary protocols to enable clinical testing of the cells.

Other authors of the paper include Yiqin Du, M.D., Ph.D., and Martha L. Funderburgh, M.S.P.H., both of the University of Pittsburgh; Eric C. Carlson, Ph.D., and Eric Pearlman, Ph.D., both of Case Western Reserve University; David E. Birk, Ph.D., of the University of South Florida; Naxin Guo, M.D., Ph.D., of the University of Rochester; and Winston W-Y Kao, Ph.D., of the University of Cincinnati.

The research was supported by grants from the National Institutes of Health, the Eye and Ear Foundation (Pittsburgh), and an unrestricted grant from Research to Prevent Blindness, N.Y. Dr. Funderburgh holds the Jules and Doris Stein Professorship from Research to Prevent Blindness.

The University of Pittsburgh School of Medicine is one of the nation’s leading medical schools, renowned for its curriculum that emphasizes both the science and humanity of medicine and its remarkable growth in National Institutes of Health (NIH) grant support, which has more than doubled since 1998. For fiscal year 2007, the University ranked sixth out of more than 3,000 entities receiving NIH support with respect to the research grants awarded to its faculty. As one of the university’s six Schools of the Health Sciences, the School of Medicine is the academic partner to the University of Pittsburgh Medical Center (UPMC). Their combined mission is to train tomorrow’s health care specialists and biomedical scientists, engage in groundbreaking research that will advance understanding of the causes and treatments of disease and participate in the delivery of outstanding patient care.

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