Month: February 2014

ThromboGenics NV (Euronext Brussels: THR), a biotechnology company focused on eye disease, vascular disease and cancer, announces promising six month follow-up results from its Phase IIb MIVI III trial, which was designed to evaluate the safety and efficacy of microplasmin in vitrectomy. The results were presented at the American Academy of Ophthalmology in Atlanta, USA, by Dr. Kirk Packo, Professor and Chairman at the Department of Ophthalmology, Rush University Medical Center in Chicago, Illinois.

The six month results from the MIVI III (MIVI III – Microplasmin for Vitreous Injection) trial continue to support the one month data previously reported, namely that the most effective dose of microplasmin studied (125 micrograms) was able to resolve the underlying disease in approximately 30% of patients without the need for vitrectomy. The six month data also show that these patients continue to do well. As anticipated, all patients in the trial who at 1 month had achieved complete resolution of vitreomacular traction or macular hole without need for surgery did not have recurrence of either traction or macular hole during the full 6 month follow up period.

The six month results also show that these patients continue to see an improvement in their visual acuity. On average, the microplasmin treated patients who had resolution of their underlying condition without need for vitrectomy achieved a 9 letter improvement when reading a standard eye chart, in comparison to the baseline reading taken prior to treatment with microplasmin. Crucially, this improvement in visual acuity is at least as good as the results seen in patients who had to undergo a surgical vitrectomy in order to resolve their underlying eye disease. These results, along with the same findings observed in the MIVI II Traction trial, represent the first ever demonstration of a pharmacologic treatment option for these conditions that would otherwise have required major eye surgery.

The MIVI III trial was a Phase IIb, randomized, double-masked, placebo-controlled, dose-ranging trial evaluating three doses of microplasmin (25, 75 and 125 micrograms) versus placebo in 125 patients scheduled for vitrectomy. The patients were recruited at 19 centers across the United States. The trial was designed to assess the safety and efficacy of microplasmin intravitreal injection given 7 days prior to the patient’s planned vitrectomy. The detailed one month results from this study were presented in June by Dr. George Williams (Beaumont Hospital, Michigan, USA) at the World Ophthalmology Congress in Hong Kong.

ThromboGenics is currently working to finalise the Phase III clinical trial program for microplasmin in the treatment of back of the eye disease, following a successful “End of Phase II meeting” with the FDA. The initial indication planned for the program is the Nonsurgical Resolution of Vitreomacular Adhesion. Two placebo controlled trials are planned, one in the U.S. and one combined European and North American trial. Together it is anticipated that the two trials will recruit a total of approximately 640 patients, with both trials expected to begin in Q1 2009. The Phase III development program will use the 125 micrograms dose of microplasmin.

Dr. Steve Pakola, Chief Medical Officer of ThromboGenics, commenting on today’s announcement, said: “We are delighted with the encouraging six month follow up data from the Phase IIb MIVI III trial. These findings support microplasmin’s potential to significantly change the treatment of a range of important back of the eye diseases. The maintained tolerability and nonsurgical benefit achieved in many of these patients highlights both the potential medical and economic value of microplasmin therapy. We look forward to confirming these important benefits in the forthcoming Phase III development program for this exciting product.”

About ThromboGenics

ThromboGenics is a biotechnology company focused on the discovery and development of biopharmaceuticals for the treatment of eye disease, vascular disease and cancer. The Company has several programs in Phase II clinical development including microplasmin, which is being evaluated as a treatment for vitreoretinal disorders and as a thrombolytic agent in stroke. ThromboGenics is also developing novel antibody therapeutics in collaboration with BioInvent International; these include TB-402 (Anti-Factor VIII), a long acting anti-coagulant, and TB-403 for cancer.

ThromboGenics has built strong links with the University of Leuven and the Flanders Institute for Biotechnology (VIB) and has exclusive rights to certain therapeutics developed at these institutions. ThromboGenics is headquartered in Leuven, Belgium and has subsidiaries in Dublin, Ireland and New York, U.S. The Company is listed on Eurolist by Euronext Brussels under the symbol THR. More information is available at thrombogenics.

Important information about forward looking statements

Certain statements in this press release may be considered “forward-looking”. Such forward-looking statements are based on current expectations, and, accordingly, entail and are influenced by various risks and uncertainties. The Company therefore cannot provide any assurance that such forward-looking statements will materialize and does not assume an obligation to update or revise any forward-looking statement, whether as a result of new information, future events or any other reason. Additional information concerning risks and uncertainties affecting the business and other factors that could cause actual results to differ materially from any forward-looking statement is contained in the Company’s Annual Report.

ThromboGenics NV
thrombogenics

Recipients of the first six grants from the new Shaffer Fund for Innovative Glaucoma Research were announced at Glaucoma Research Foundation’s 30th Anniversary Benefit. The Shaffer Grants expand Glaucoma Research Foundation’s longstanding commitment to one-year incubation grants. Additionally, Mark Filla PhD (University of Wisconsin, Madison) was named as the inaugural recipient of the new Shaffer Prize for Innovative Science, as a result of recent research funded by the Glaucoma Research Foundation (GRF).

“In August, 2007, we all mourned the loss of Dr. Robert N. Shaffer, one of the nation’s great pioneering glaucoma physicians,” said GRF President and CEO Thomas M. Brunner. “In 1978, Dr. Shaffer co-founded the Glaucoma Research Foundation with Drs. H. Dunbar Hoskins Jr. and John Hetherington, to seek better treatment options for glaucoma patients.”

In 1993, GRF launched its Pilot Project Grants program, offering one-year research grants to explore novel or promising ideas in the study of glaucoma. Altogether, more than 120 Pilot Project grants have been awarded, producing more than 100 peer-reviewed papers published in scientific journals.

With the passing of Dr. Robert Shaffer and the desire to permanently imbue his founding spirit of serving glaucoma patients, the GRF Board of Directors has renamed the Pilot Project grants “The Shaffer Fund for Innovative Glaucoma Research.” First recipients of the new Shaffer Grants are:

– Paul Habib Artes, PhD, Dalhousie University, Halifax, NS, Canada – “Analysis of Progression in Glaucoma”

– Jamie Craig, PhD, Flinders University of South Australia – “Genome-wide association in Primary Open Angle Glaucoma: The Blindness in Glaucoma Genetic Epidemiology Relative Risk Study”

– Brad Fortune, OD, PhD, Devers Eye Institute, Portland, OR – “Imaging the course of axonal degeneration in experimental glaucoma”

– Kate E. Keller, PhD, Casey Eye Institute, Portland, OR – “RNAi gene silencing of enzymes in the glycosaminoglycan biosynthetic pathway”

– Raquel L. Lieberman, PhD, Georgia Institute of Technology, Atlanta, GA – “Development of pharmacological chaperone therapy for inherited primary and juvenile open angle glaucoma”

– Yutao Liu, MD, PhD, Duke University Medical Center, Durham, NC – “Investigation of gene copy number variants in primary open-angle glaucoma.”

The Shaffer Prize for Innovative Science

The memory of Dr. Shaffer was further reinforced by creating “The Shaffer Prize for Innovative Science,” to be selected annually by the GRF Scientific Advisory Committee (SAC).

Mark Filla, PhD (University of Wisconsin – Madison) was selected by the GRF SAC to receive the first Shaffer Prize for Innovative Science, based on the results of his research funded by a Pilot Project grant awarded in January 2006. “Dr. Filla’s work examined the ability of specific cell surface receptors to cause rearrangements in the intracellular skeletal system of the cells that regulate aqueous humor outflow from the eye,” explained SAC Chair, George Cioffi, MD, Director Chief Medical Officer and Vice President of the Devers Eye Center in Portland.

The results of Filla’s research, Cioffi said, were selected for publication in the July 2006 edition of Investigative Ophthalmology and Visual Science, and point the way to possible new therapies less likely to elicit side effects. Results from Dr. Filla’s Pilot Project led to grants from the National Institutes of Health, and the National Eye Institute, enabling Filla to continue this valuable research, Cioffi said.

In addition to Cioffi, members of the Scientific Advisory Committee selecting the grantees and naming the Shaffer Prize winner are: Balwantray Chauhan PhD, Dalhousie University, Nova Scotia; Anne Coleman, MD, PhD, Jules Stein Eye Institute, Los Angeles; Christopher Girkin, MD, University of Alabama at Birmingham; Sayoko Eileen Moroi, MD, PhD, University of Michigan, Ann Arbor; Harry Quigley, MD, Wilmer Eye Institute, Baltimore; Joel Schuman, MD, University of Pittsburgh; Ernst Tamm MD, University of Regensburg, Germany; Douglas Vollrath MD, PhD, Stanford University; Arthur Weber, PhD, Michigan State University, East Lansing; Robert Weinreb, MD, University of California, San Diego; and Janey Wiggs, MD, PhD, Massachusetts Eye and Ear Infirmary, Boston.

About The Glaucoma Research Foundation

Glaucoma is the leading cause of preventable blindness. Founded in 1978 in San Francisco, the Glaucoma Research Foundation works to prevent vision loss from glaucoma by investing in innovative research, education, and support with the ultimate goal of finding a cure.

Glaucoma Research Foundation

The visual system has limited capacity and cannot process everything that falls onto the retina. Instead, the brain relies on attention to bring salient details into focus and filter out background clutter. Two recent studies by researchers at the Salk Institute for Biological Studies, one study employing computational modeling techniques and the other experimental techniques, have helped to unravel the mechanisms underlying attention.

“In everyday viewing a visual detail that is the target of our attention is generally surrounded by a lot of stimuli that are momentarily irrelevant to behavior,” says John H. Reynolds, Ph.D., an associate professor in the Systems Neurobiology Laboratory at the Salk Institute, who led the study published in the March 26, 2009 issue of the journal Neuron. “Attention dynamically routes relevant information to decision-making areas in the brain and suppresses the surrounding clutter.”

But just how the brain achieves this feat has been the topic of much debate. In an earlier issue of Neuron, Reynolds and David J. Heeger, Ph.D., a professor in the Department of Psychology and the Center for Neural Science at NYU, put forth a new theoretical model of attention. Their model suggests that attention co-opts the same neural circuitry used by the visual system to adjust its sensitivity, which allows us to perceive the world irrespective of huge changes in contrast and illumination over the day.

“The central role of attention in perception has been known since the dawn of experimental psychology. An enormous amount of research has been done on the subject, but ostensibly conflicting experimental data have bewildered researchers for years,” says Reynolds. “Our model brought what seemed like a hodgepodge of observations together within a simple framework, and our latest study tested and confirmed predictions of the theory.”

The strength of visual input fluctuates over orders of magnitude. The visual system reacts automatically to these changes by adjusting its sensitivity, becoming more sensitive in response to faint inputs, and reducing sensitivity to strong inputs. For example, when we walk into a darkened lecture hall on a sunny day at first we see little, but over time our visual system adapts, increasing its sensitivity to match the environment.

A subtler version of this is the so-called contrast gain control. “Spend a few minutes staring at an Ansel Adams photograph. You will find that your visual system will adapt to low-contrast parts of the image, revealing subtleties that were invisible at first,” explains Reynolds.

Heeger proposed a simple but powerful model of the cortical circuitry that helps mediate this form of automatic gain control. “We believe that this circuitry has been co-opted through evolution, enabling the brain to exploit the same circuitry to adjust its sensitivity endogenously,” says Reynolds. “It doesn’t just adjust sensitivity in response to changes in input strength, it also enables the brain to emphasize task-relevant information and suppress neuronal signals driven by task-irrelevant clutter.”

Neurons in the visual cortex view the world through their “receptive fields,” the small portion of the visual field individual neurons actually “see” or respond to. Whenever a stimulus falls within the receptive field, the cell produces a volley of electrical spikes, known as “action potentials” that convey information about the stimulus in the receptive field.

But the strength and fidelity of these signals also depends on other factors. Scientists generally agree that neurons typically respond more strongly when attention is directed to the stimulus in their receptive fields. In addition, the response of individual neurons can be strongly influenced by what’s happening within the immediate surroundings of the receptive field, a phenomenon known as contextual modulation.

“The surround has the ability to suppress the neuron’s response,” explains first author Kristy Sundberg, Ph.D., a former graduate student in Reynolds’ lab and now a postdoctoral researcher at Yale University. “It keeps us from responding all the time if there’s something that’s big and uniform and not particularly interesting or useful. This raised the possibility that the receptive field surround might provide a way to suppress the responses of task-irrelevant distracters.”

To get to the bottom of this, Sundberg set up a series of experiments in which she placed one stimulus in the receptive field and another in the surround. As predicted by Reynolds’ and Heeger’s theory, she found that directing attention to the center stimulus immunized the neuron from the suppressive effects of the stimulus in the surround. When she instead directed attention to a stimulus in the surround, it suppressed the neuron’s response to the task-irrelevant stimulus in the center.

“The attentional system exploits the center-surround organization of the receptive field to keep neurons that transmit task-relevant information from being suppressed by distracters in the environment, while at the same time suppressing the responses of neurons that respond to irrelevant clutter,” says Sundberg. “The brain uses the receptive field surround actively to separate the wheat from the chaff.”

Notes:

Jude F. Mitchell, Ph.D., a postdoctoral researcher in Reynolds’ lab also contributed to the study.

The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health, and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.

Source:
Gina Kirchweger

Salk Institute

Current research suggests that melatonin therapy may help treat uveitis, a common inflammatory eye disease. The related report by Sande et al., “Therapeutic Effect of Melatonin in Experimental Uveitis,” appears in the December issue of The American Journal of Pathology.

People with uveitis develop sudden redness and pain in their eyes, and their vision rapidly deteriorates. Untreated, uveitis can lead to permanent vision loss, accounting for an estimated 10-15% of cases of blindness in the US. Uveitis has a wide variety of causes, including eye injury, cancer, infection, and autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. There is currently no optimal treatment for uveitis. Corticoid steroid eye drops are often used; however, long-term corticoid use has many negative side effects, including the possible development of glaucoma.

Researchers lead by Dr. Ruth Rosenstein of The University of Buenos Aires and The National Research Council (CONICET) hypothesized that melatonin, which regulates sleep/wake cycles and reduces jet lag, may be able to prevent the ocular inflammation in uveitis. They found in an experimental model of uveitis that levels of two factors that contribute to inflammation, TNF?� and NF??B, were reduced with melatonin treatment. Importantly, melatonin treatment also decreased the appearance of clinical symptoms of uveitis such as inflammation, blood vessel expansion and cataract, and protected the blood-ocular barrier integrity.

Taken together, the data from Sande et al suggest that “melatonin, which lacks adverse collateral effects even at high doses, could be a promising resource in the management of uveitis. Alone or combined with corticosteroid therapy, the anti-inflammatory effects of melatonin may benefit patients with chronic uveitis and decrease the rate and degree of corticosteroid-induced complications.” Future studies will aim at understanding the mechanisms governing melatonin protection in the eye.

This work was supported by grants from the Agencia Nacional de Promoci??n Cient?�fica y Tecnol??gica (ANPCyT), the University of Buenos Aires, CONICET, Argentina, and the John Simon Guggenheim Memorial Foundation.

Sande PH, Fernandez DC, Aldana Marcos HJ, Chianelli MS, Aisemberg J, Silberman DM, S??enz, DA, Rosenstein RE: Therapeutic effect of melatonin in experimental uveitis. Am J Pathol 2008 173:1702-1713

The American Journal of Pathology, official journal of the American Society for Investigative Pathology, seeks to publish high-quality, original papers on the cellular and molecular biology of disease. The editors accept manuscripts that advance basic and translational knowledge of the pathogenesis, classification, diagnosis, and mechanisms of disease, without preference for a specific analytic method. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, animal, biological, chemical, and immunological approaches in conjunction with morphology.

Source: Angela Colmone

American Journal of Pathology

ESBATech AG, a leading developer of antibody fragment therapeutics,
announced that the company has successfully completed its Phase I clinical
study of the company’s lead product candidate, ESBA105, in ophthalmic
indications. In April 2008, ESBATech initiated the Phase I study designed to
evaluate the safety, tolerability and pharmacokinetic profile of ESBA105,
when delivered topically via eye drops in healthy volunteers. This trial was
conducted as a single and repeated dose escalation study in Switzerland.
ESBA105 is a single-chain antibody fragment directed against TNF-alpha, and
it is being developed initially for ophthalmic indications. Several
additional clinical studies are in the preparation stages.

Manfred Zierhut, Professor in the Department of Ophthalmology at the
University of Tuebingen in Germany, will present preclinical pharmacokinetic
data on ESBA105 on Friday, September 12, 2008, at the 7th International
Symposium on Uveitis in Constance, Germany. For more information on the
symposium and on Prof. Zierhut’s abstract, please visit iusg2008.

Dominik Escher, Ph.D., Chief Executive Officer of ESBATech AG, commented,
“The completion of this Phase I study with ESBA105 in ophthalmic indications
marks a critical clinical milestone for the company. Recently, ESBATech
secured CHF 23M (USD 22M) in an extended Series B venture financing round.
This financing will fund further clinical studies with ESBA105 in ophthalmic
indications, as well as build broad franchises in ophthalmology, rheumatology
and respiratory diseases for ESBA105 and other antibody fragments. We look
forward to announcing the results of this Phase I study and future clinical
trials.”

Peter Lichtlen, M.D., Ph.D., Head of Clinical Development at ESBATech AG,
commented, “We are encouraged by the safety and pharmacokinetic profile that
ESBA105 has demonstrated in this Phase I study and we look forward to
continuing our progress in the clinical development of this product.”

About ESBATech AG

ESBATech AG is a Zurich, Switzerland-based, privately held drug discovery
and development company focused on advancing antibody fragments for
therapeutic applications. The company applies its proprietary, fully human
single-chain antibody frameworks to generate product candidates against
targets of clinical relevance. ESBATech is focused on delivering high
concentrations of its therapeutic antibody fragments to the targeted sites,
in combination with extremely low systemic load, in order to achieve low risk
of systemic drug reactions using topical and local delivery.

Current venture investors include SV Life Sciences, Clarus Ventures, HBM
BioVentures, HBM BioCapital, Novartis Bioventures, BioMedinvest and VI
Partners. For more information about ESBATech, please visit,
esbatech.

ESBATech AG

Can The US Really Cut Health Care Spending?

A new study suggests that while health care is one of the strongest sectors of the ailing US economy, achieving a substantial, sustainable reduction is US health care spending is not probable. The author, who completed health care policy literature and position article reviews, reveals that despite far greater expenditures, US hospitalization rates, lengths-of-stay, and inpatient hospital beds are all lower than they are in other first-world nations. Furthermore, Americans pay higher prices for the same health services than citizens in other countries – including Canada. The study outlines steps that could be taken by the US to reduce spending, but contends that unless Americans are willing to discuss and accept restrictions and/or limitations on health care, spending growth is unlikely to decrease. This study appears in the January 2009 issue of Plastic and Reconstructive Surgery, the official medical journal of the American Society of Plastic Surgeons.

By The Numbers:
According to ASPS statistics, $12.4 billion was spent on elective cosmetic procedures in 2007.

In 2007, the Centers for Medicare and Medicaid Services estimated that health care spending in the US reached $2.2 trillion – and is projected to exceed $4 trillion by 2017.

Medicine Cabinet Mainstays Pose Risks to Cosmetic Surgery Patients

Common antidepressants and herbal medications may have potentially harmful intraoperative effects on patients undergoing cosmetic surgical procedures, according to a new study. Researchers from New York conducted and reviewed case studies regarding the effects of the 29 most commonly used herbs and antidepressants, on anesthesia and surgery. After identifying a number of harmful, intraoperative risks, ranging from increased bleeding to fatal interactions, the authors established recommendations for the management of these medications before elective surgery. The authors suggest that patients using those antidepressants and herbs noted in the study consult with the prescribing physician about discontinuing use for up to two weeks prior to surgery. This study appears in the January 2009 issue of Plastic and Reconstructive Surgery, the official medical journal of the American Society of Plastic Surgeons.

By The Numbers:
According to ASPS statistics, 11.8 million cosmetic procedures were performed in the US in 2007.

In 2005, the National Center for Health Statistics (NCHS) estimated that $118 million of the $2.4 billion spent of prescription medications was on antidepressants.

In 2000, it was identified that 32% of the ambulatory surgery population used herbal medications, according to the NCHS.

Preventing and Managing ‘Dry Eye’

New research evaluates the development of dry eye syndrome and outlines the proper steps for the detection, prevention and management of the affliction. During the study, researchers from Texas and Florida conducted a chart review of 202 patients who underwent upper and lower eyelid surgery, and collected data that identified the risk factors associated with dry eye symptoms. While such symptoms are temporarily common in most eyelid surgery patients, they are expected to last for only a few days. However, 10% of patients in the study group experienced dry eyes for 2 weeks or longer. Researchers identified the use of contact lenses, premenopausal state, and history of laser-assisted vision correction among the risk factors for persistent dry eye symptoms. They suggest that proper understanding of anatomy, preoperative recognition of risk factors, intraoperative maneuvers, and immediate and aggressive postoperative management are key to minimizing the occurrence of chronic dry eye in these patients. This study appears in the January 2009 issue of Plastic and Reconstructive Surgery, the official medical journal of the American Society of Plastic Surgeons.

By The Numbers:

In 2007, 241,000 eyelid surgeries were performed in the US, according to ASPS statistics.

Source: ASPS Public Relations

American Society of Plastic Surgeons

Researchers in Singapore have reported an outbreak of Fusarium keratitis (a fungal infection of the cornea) associated with soft contact lens wear and linked with use of certain contact lens cleaning solutions, according to an article in the June 28 issue of JAMA.

Keratitis, an inflammation of the cornea, is a potentially blinding infection and is one of the most severe complications associated with contact lens use. However, outbreaks of fungal keratitis are rare in contact lens wearers. Since March 1, 2005, Singapore has seen a sharp increase in the number of keratitis cases caused by the Fusarium fungus species. Recent reports have also confirmed that 122 patients in the U.S. and 33 in Hong Kong have developed Fusarium keratitis, suggesting that this outbreak may be part of a global problem for contact lens wearers, according to information in the article.

Wei-Boon Khor, M.B.B.S., of the Singapore Eye Research Institute, and colleagues examined the Fusarium keratitis outbreak in Singapore. All cases of fungal keratitis among contact lens wearers from March 2005 through May 2006 were included in the study. Researchers collected corneal samples and patients’ contact lenses, lens cases and current bottle of contact lens solution for testing. Telephone interviews were also conducted.

During the 15-month period, 66 contact lens wearers (68 affected eyes) were diagnosed with Fusarium keratitis. From this, the researchers estimated that the annual national incidence of Fusarium keratitis was 2.35 cases for every 10,000 contact lens wearers in Singapore. Nearly all patients wore soft, disposable contact lenses (98.5 percent) and a high proportion (93.9 percent) reported using ReNu brand cleaning solution, including 42 patients (63.6 percent) who reported using ReNu with MoistureLoc. Most patients (81.8 percent) had poor lens hygiene habits, including wearing daily contacts overnight, wearing expired lenses and wearing contacts while swimming. The authors suggest that these habits, however, cannot fully account for the outbreak. Two-thirds of patients (n = 44) had severe, sight-threatening lesions requiring an average first-visit hospital stay of 6.5 days, and five patients required corneal transplantation.

“We believe that Singapore is facing a new and unprecedented outbreak of Fusarium keratitis and that this is the first time that such an outbreak has been reported among contact lens wearers anywhere in the world,” the authors write. “A national case-control study currently under way will shed further light on the probable risk factors for this outbreak, including the role of contact lens solutions.” The authors conclude by encouraging physicians and clinicians to “maintain a high index of suspicion for fungal infection when evaluating and treating patients with contact lens-associated microbial keratitis.”

(JAMA. 2006; 295: 2867 – 2873.

Contact: Donald T.H. Tan, F.R.C.S.

JAMA and Archives Journals

Last night the Foundation Fighting Blindness honored two outstanding individuals, Jennifer Rothschild and Dr. Stephen J. Ryan, for their contributions to the vision impaired community at the 7th Annual “For the Love of Sight” Valentines Party. Emmy Award-winning journalist and bestselling authorCokie Roberts and her husband, George Washington University professor and fellow journalist Steve Roberts, served as the evening’s emcees. Also in attendance were actor Val Kilmer, Senator Robert Bennett and his wife Joyce, Senator Kit Bond and his wife Linda, Senator Arlen Specter, Congressman Russ Carnahan and his wife Debra, Congressman Danny Davis and his wife Vera, Congresswoman Sheila Jackson Lee, Congressman Jerry Lewis and his wife Arlene Willis, Congressman Pete Sessions, Acting Secretary of the Department of Health and Human Services Charles Johnson, Former Director of the Office of Management and Budget Jim Nussle and his wife Karen, and Director of the National Eye Institute Paul A. Sieving, M.D., Ph.D.

Jennifer Rothschild, author, songwriter and mother who suffers from a rare degenerative eye disease that has rendered her blind, was thrilled to receive the Foundation’s Hope and Spirit Award and said, “It is a great honor to be recognized by such a distinguished group. The Foundation’s successful efforts towards funding new and critical research will help me and the more than 10 million Americans who struggle with vision loss eventually regain our sight. I am proud to be part of this exciting and important group, as well as tonight’s event.”

The Foundation’s Visionary Award was presented to Dr. Stephen J. Ryan, founding President of the National Alliance for Eye and Vision Research and an internationally recognized expert in the field of retinal diseases and ocular trauma. “I want to thank the Foundation Fighting Blindness for the critical funding they provide to doctors and researchers. Through their continued efforts, I am hopeful that we will be capable of finding a cure for these devastating diseases in the near future,” said Dr. Ryan.

The “For the Love of Sight” Valentine’s Party benefits the Foundation Fighting Blindness, a national non-profit organization and the largest source of non-governmental funding for retinal degenerative disease research in the world. The Foundation has already paved the way for groundbreaking studies of gene therapy that has restored sight in dogs and now, in clinical trials, is restoring sight in humans. Past “For the Love of Sight” events have raised almost $2.5 million for the Foundation’s mission.

.

About the Foundation Fighting Blindness

The mission of the Foundation Fighting Blindness is to drive the research that will provide preventions, treatments and cures for people affected by retinitis pigmentosa (RP), macular degeneration, Usher syndrome, and the entire spectrum of retinal degenerative diseases. Over 10 million Americans suffer vision loss from these diseases. The Foundation funds leading-edge research in promising areas such as genetics, gene therapy, retinal cell transplantation, and pharmaceutical and nutritional therapies. Since its inception in 1971, the Foundation has raised over $350 million.

Important Facts:

– Over 10 million Americans of every age and race suffer vision loss from blinding diseases. With the aging population, that number is expected to increase 50% by 2020.

– Age-related macular degeneration, characterized by a progressive loss of central vision, is the leading cause of legal blindness in adults over age 55.

– RP and Usher syndrome are inherited diseases commonly diagnosed during childhood or young adulthood.

– RP causes severe vision loss leading to legal and/or complete blindness.

– Children with Usher syndrome are born with varying degrees of deafness and later develop RP.

About the 7th Annual For the Love of Sight Valentine’s Party

– Emcees – Cokie and Steve Roberts

– Awards – Hope and Spirit Award presented to Jennifer Rothschild and the Visionary Award presented to Dr. Stephen J. Ryan

– Event Chairs – Bill and Colleen Carty, Susan Davis, Gordon and Llura Gund, Carlos and Edilia Gutierrez, Ann McLaughlin Korologos and Tom Korologos, and Ken Rietz and Ursula Landsrath

– Dinner Committee Members include: John Brady and Margaret Kirk Brady, Connie Falvo, Dave and Pam Foley, George and Molly Franklin, Ed and Sandy Gollob, Manuel and Mary Johnson, B.R. and Laura McConnon, Steve McMahon and Cynthia Alksne, Tom Nides and Virginia Moseley, Brad and Uyen O’Leary, Dick and Debby Patrick, Basil and Karen Petrou, Abe and Irene Pollin, The Catherine B. Reynolds Foundation, Terry and Brooke Ross, Fred and Jeri Thompson, and, Ed and Carole Walter.

Foundation Fighting Blindness

Diabetic retinopathy could be associated with poorer memory and diminished brain power in people with Type 2 diabetes, according to new research announced this week at Diabetes UK’s Annual Professional Conference.

The study looked at 1,066 people with Type 2 diabetes aged between 60 and 75 years. Participants completed seven tests looking at memory, logic and concentration to establish their level of brain function. Those with retinopathy had worse average scores on most of the individual tests as well as on general cognitive ability compared to those without the condition. The results were independent of age and gender.

What this means

Mrs Jie Ding from the University of Edinburgh, who helped lead the research (as part of the Edinburgh Type 2 Diabetes Study), said: “These findings suggest that the severity of diabetic retinopathy is independently associated with cognitive dysfunction in people with Type 2 diabetes aged between 60 and 75 years old.

“This can mean either that cerebral microvascular disease, as indexed by retinopathy, may lead to cognitive decrements in old age or that poorer cognitive ability makes diabetes management more difficult, and in turn promotes the development of cerebral microvascular disease.

“It is also possible that a third unidentified factor is causing both diabetic retinopathy and the cognitive changes. The four-year follow-up data of the ET2DS study may clarify the temporal relationship of these associations. The seven neuropsychological tests assessed people’s memory for faces, recollection of linear stories, vocabulary, the ability to re-organise a sequence of letters as well as some other cognitive functions.

“The results provide insights into the specific underlying mechanism of cognitive dysfunction in Type 2 diabetes, which is possibly due to a break-down of blood brain barrier (similar to changes in blood-retinal barrier as seen in diabetic retinopathy). From a clinical perspective, cognitive impairment in Type 2 diabetes may therefore be amenable to treatment and preventive strategies targeted at this small vessel disease.”

Adding to body of research

Dr Iain Frame, Director of Research at Diabetes UK, said: “Retinopathy is an indicator of cerebral microvascular disease, which is when the small blood vessels in the brain are narrowed or blocked off and lead to a reduction in blood supply to the brain tissues. There is already evidence to suggest that cerebral microvascular disease and Type 2 diabetes may exacerbate the effects of aging on cognitive function.

“This study adds to this body of research as it suggests that diabetic retinopathy is linked to estimated life time cognitive decline in older people with Type 2 diabetes.

“Cognitive decline is the decline of brain functions such as memory, attention, and planning.

“If anyone with diabetes is concerned about their health they should consult their GP or diabetes healthcare professional.”

Retinopathy and Type 2 diabetes in the UK

There are 2.35 million people diagnosed with Type 2 diabetes in the UK and up to 500,000 who have the condition but do not know it. Almost two thirds of the 2.35 million people with Type 2 diabetes develop some degree of retinopathy within 20 years of being diagnosed.

Source
Diabetes UK

For some years now a small group of scientists have been pioneering a revolutionary idea that the vertebrate immune system could have a role in the regulation of iron in the body. And now, a work soon to be published in the journal Immunology, shows that human lymphocytes (white blood cells) actually produce hepcidin, the most important protein in the regulation of iron levels in the body. What was also unexpected was the fact that hepcidin affected lymphocyte multiplication which occurs for example during an infection showing that the two systems seem to be much more interlinked than even previously imagined.The discovery has far reaching implications as Jorge Pinto, the first author of the study, resumes: ” from new players in both iron metabolism and immunology to a new understanding of how cell division in itself is controlled (both normal cell division and cancer) to even help us to better understand the evolution of the immune system”. The work comes from a team of Porto University, Portugal, led by Maria de Sousa, the scientist that first proposed the idea of a link between the immune system and iron homeostasi.

Thirty years ago Maria de Sousa, then at the beginning of her career, noticed that lymphocytes were attracted to places with surplus of iron. This, together with

1. the fact that the vertebrate immune system (IS) was incredibly more complex that those of its ancestors (and evolution rarely increases complexity, which is energetically costly, unless something is gained)

2. the IS unique capacity to reach everywhere in the body

led her to a revolutionary new idea – could this new complexity be evolutionary sound, because it allowed the IS to perform some important new function, maybe protecting the body against iron toxicity?

In fact iron, although an essential element for most life forms, can also be toxic to these same organisms when free (not attached to proteins). This means that in this form it needs to be “watched” and regulated around the clock. In vertebrates, this is done through hepcidin, a liver protein that “moves” iron between cells and plasma according to the body needs (or potential dangers). The problem is that the hepcidin liver cells have limited mobility so a complementary far reaching iron control system was needed. Lymphocytes, with their unique capacity to move throughout the body were the perfect candidates and since 1978, de Sousa and her group have been chasing this idea.

Much of their work has been done on hemochromatosis a disease where there are problems in the absorption of iron through the digestive track leading to too much iron in the organism and to its toxic accumulation in the organs.

From this work we know now that hemochromatosis patients also have a defective IS, and more, that their iron overload levels correlate with their lymphocyte deficiency the less lymphocytes they have the more severe the disease. Work in animal models with iron overload problems or instead, with lymphocyte deficiencies have again found links between excess of iron in the body and deficient IS further supporting de Sousa’s “immuno-iron idea”.

And meanwhile, human lymphocytes were shown to produce several proteins crucial for the regulation of iron levels ferritin, which acts as the body storage of iron (so holding to it when there is too much in the body or releasing it when there is deficiency) and ferroportin, which is the cells’ iron “exit door” (again releasing or retaining iron as necessary) . The fact that lymphocytes had both proteins gave them the potential to be a “mobile” and easily “mobilizable” iron-storage compartment, characteristics perfect for an important role in iron homeostasis.

Nevertheless, the exact mechanism how this could happen remained elusive

But hepcidin, the central piece of iron regulation, is known to be also an important player in the immune response what has raised the possibility that it could be in it the clue to this problem. In fact, during infection hepcidin shuts down the “door” through which iron leaves the cell (ferroportin) reducing iron availability in the plasma and thus helping to control infection as bacteria need iron to divide. And now several studies have shown that hepcidin is produced by a variety of cells involved in the immune response. Finally, last year, a study suggested, for the first time, that lymphocytes were also capable of producing the protein putting the possibility that hepcidin could actually be “the missing link” of de Sousa’s theory.

To clarify this hypothesis Jorge Pinto, Maria de Sousa and colleagues at the Institute for Molecular and Cell Biology (IBMC) of Porto University looked at hepcidin production in human lymphocytes in situations of toxic iron concentrations or immune activation, as de Sousa’s theory proposed that lymphocytes could play a role in both situations. They found that hepcidin not only was produced by all classes of lymphocytes, but also that its production increased both in the presence of high quantities of iron, and when lymphocytes were activated, backing de Sousa’s proposals.

Pinto explains: “We show, for the first time, that lymphocytes can “feel” the toxic levels of iron in circulation and respond by increasing their own capacity to retain it within, restoring “normality”. The same mechanism is seen being used in situations of (iron) demand, such as when the cells are activated by the occurrence of an infection and need to divide.”

They also found something else totally unexpected that hepcidin was involved in this second mechanism, suggesting an even closer dependence between the two systems than de Sousa had thought.

To Hal Drakesmith, a researcher at the University of Oxford working on the possibility of manipulating iron transport as a way to combat infections such as HIV, malaria and Hepatitis C these results raise particularly interesting questions as he explains “This seems to suggest that control of iron metabolism may be an integral component of lymphocyte immunity. Withholding iron from pathogens is an accepted part of our defence against infection, but a role for lymphocytes in controlling iron transport has not been proposed before.

“Crucially – says Pinto we still believe that the main regulator of systemic iron levels is the liver but not only are lymphocytes (and not liver cells) able to sense toxic forms of iron, but they are also able to travel and be activated in specific places where the pathogens accumulate helping to control infection. “

These results are a major step to understand the link between the IS and iron and, if confirmed in live organisms all this work was done on human cells in the laboratory can be the beginning of a totally different view of what the immune system is and how to approach immunologic problems.

As Hal Drakesmith says “the paper describes several new findings which are highly likely to be of interest and importance to the iron and immunity fields of research” A simple example is the anaemia that usually accompanies chronic inflammatory diseases and that so far can not be clearly explained. Pinto and Sousa’s results suggest that lymphocyte chronic activation, so characteristic of these diseases, by leading to hepcidin production could be part of the phenomenon as iron is an integral part of red blood cells.

Pinto, de Sousa and colleagues now plan to go back to those diseases of iron overload associated to immune abnormalities and see if hepcidin proves to be, in fact, the connection between them. Other possibility is the construction of mice without the hepcidin gene in the bone marrow where lymphocytes develop to analyse the changes that this could bring to both iron homeostasis and the immune response.

Whatever happens this is a strikingly interesting story with decades of persistence and believe behind it and which, I am sure, still has much to tell us.

Source: Ci??ncia Viva