El propósito de este sitio es proporcionar información y recursos que ayudarán a aquellos diagnosticados con lupus mejor comprender y manejar esta enfermedad, al igual que ayudar a aquellos que vienen a nosotros para recibir información. Queremos proporcionarle los recursos educativos más actuales e informativos. Creemos que nuestros programas y servicios son una fuente de estímulo y poder. Nuestra meta es mejorar la calidad de vida para aquellos afligidos con lupus a través de educación, servicios, concienciación y trabajo comunitario, y apoyo a la investigación que resultará en mejores tratamientos y, algún día, en una cura.

Estamos en el proceso de traducir las páginas de este sitio y de poder ofrecerles más y más información y recursos en español muy pronto.

Support Groups - Our support groups are held throughout Nassau, Suffolk and Queens. A professional counselor who is also a person with lupus facilitates these groups. For a list of support group locations and times.

LupusLine Long Island- Queens - a free telephone peer counseling service for people with lupus and their families.

New Patient Orientation- Free classes for newly diagnosed people with lupus, their families and friends are held every other month at the chapter office. Please check the calendar for dates.

Education Day Programs - An all day education program on lupus that helps participants learn the medical facts about Lupus and how to live with this chronic illness. The group is limited in size so that experiences can be shared.

Doctor Referral List - Our Alliance provides a list of specialists in Rheumatology and dermatology who have indicated an interest in treating individuals with lupus. This list contains physicians in Nassau, Suffolk, Queens, Brooklyn and Manhattan. Call our office and we will help you locate a doctor in your area.

If you would like to research a rheumatologist in your area go to:
http://www.rheumatology.org/directory

If you would like to research a dermatologist go to: http://www.aad.org

Newsletters -The Lupus News Link is mailed quarterly to people with lupus, their families, health care professionals, and clinics. The newsletter gives current information about lupus, research updates, volunteer opportunities, chapter events and more.

Seminars - An annual seminar, as well as periodic workshops, is specifically designed to meet the needs of the lupus community. Presentations are by both medical and business professionals. Topics are based on requests from members and participants. Dates, topics and locations appear in our newsletter and in our calendar.

Resource Library - Books on the various aspects of lupus are available for purchase. Members are also able to borrow books and videos from the Alliances lending library.

Financial Assistance Program - The Quality of Life program was developed in 2000 to help individuals with lupus meet needs that are not covered by other resources. Inquiries regarding the eligibility and availability of this program may contact our office at 1-800-850-9000. This program is limited in scope and as a source of last resort.

Speakers’ Bureau - Trained speakers are available to address professionals, schools and personal groups about lupus and the Lupus Alliance, Long Island/Queens Affiliate. No group is too large or too small. Call our office to schedule a speaker.

Kids Programs - Our “Let Kids be Kids” program is available to children 7-17 who have lupus or a family member with lupus. Day trips to fun places are planned, transportation included. Scholarships are also available to children afflicted with lupus who have special needs that cannot be covered by other means.

Spanish speaking staff

Wheelchairs Available. We now have 4 wheelchairs that have been donated to this office. If anyone has a need for one, they will be available for borrowing. Please contact the office to request one.

Phone: 516-783-3370 or1-800-850-9000

Fax: 516-826-2058
Email: info@lupusli.org, info@lupusliqueens.org

A copy of our annual report may be obtained, upon request, from the Lupus Alliance or from the Office of the Attorney General, Charities Bureau, 120 Broadway, New York New York 10027. For a copy of our 990 and financial information go to www.guidestar.org

Friday 9:30AM - 4:00 PM

Around eight years ago, Human Genome Sciences survived the first event, when patients were first given the firm's experimental lupus treatment. Sometime in July, and many hundreds of millions of dollars later, they will gather in a hotel conference room to see how they endured the second crucial event -- final human testing results. David Stump, the firm's head of drug development, is hoping the first PowerPoint slide the biostatistician shows will say success.

"You work yourself into a zone of contemplation," Stump said. "It is one of those acquired skills you develop in this business. You have to make your peace with success and failure. If you can't make your peace with failure, then this isn't the business you should be in."

And plenty of people on Wall Street predict that the Rockville company will fail. Lupus, a complicated autoimmune disease in which the body attacks its organs, is known as the drug industry's black hole, where even the world's top scientists go to fail. There hasn't been a new lupus drug approved in 50 years. Not long ago, biotech behemoth Genentech stumbled with its own candidate.

"No one has any real conviction that HGS's drug is going to work," said Geoffrey Porges, a Sanford C. Bernstein analyst. "Nothing has really ever worked in lupus. It's a very difficult disease." In downgrading the stock recently, Lazard Capital Markets analyst Terence Flynn told investors, "We continue to believe that the probability that this drug succeeds is extremely low."

The difficulty in going after lupus is that the disease waxes and wanes, heightening the possibility of a placebo effect. Also, because many organs are involved, it is difficult to measure success because the disease is a moving target. In cancer, drug developers generally target stationary tumors with a laser focus. Treating lupus is like trying to corner a hyper cat.

In key mid-stage testing in 2005, HGS fell short of the goal line. But when executives took a closer look at the data, they saw that their drug, now called Benlysta, was successful in treating a subset of patients who had biologic indicators in their blood showing that the disease was active. Wall Street analysts generally dismiss such retrospective analysis.

"It's changing the rules of the race," Porges said. "We lost the marathon, but if it had been a half marathon, we would have won."

Nonetheless, in the final stage of testing, HGS, with the agreement of federal regulators, only enrolled that subset of patients in the study. Stump said that if what happened in the retrospective analysis of the earlier failed study repeats itself, "We will have very favorable results." But there is still room for doubt, he said: "The patient variability component is still there." Translation: The cat is always on the move.

HGS chief executive H. Thomas Watkins said Wall Street's reservations did not bother him. He pointed to recent positive results from an extension of the last study, which showed that for patients who stayed on the drug, after four years there was sustained improvement in the disease.

"The consensus out there may be that we shouldn't count on it working, but that doesn't change the prospect of it working," Watkins said. "Our chances of success are independent of what the market thinks." Later in the interview, he said, "It will succeed, it will succeed," almost like a mantra.

The stakes for HGS and lupus patients are enormous. For the company, it would be a significant validation of the founding principles of genomic medicine, but more importantly it would provide a much-needed source of revenue for a firm whose only product on the market is a treatment for anthrax. A lupus drug has the potential to become a billion-dollar drug. HGS is also working on a treatment for hepatitis C, though that drug has also been criticized by some analysts.

Hanging over HGS's head: About $400 million in convertible debt due in 2011 and 2012 if the company's shares don't trade for more than $15. HGS shares are currently trading for under $3. Analysts who are less negative about the company's prospects for success in lupus say a positive study result could send the shares over $20. "In our view, this could be a tremendous opportunity if the data is positive," Citigroup analyst Yaron Werber recently told investors.

Then there's the lupus patients, who haven't had a new drug in five decades and who currently take a combination of drugs with serious side effects. "The patients are very excited," said Sandra Raymond, president of the Lupus Foundation of America. "They have waited a long time, so this is a very exciting prospect. I believe we will have a new medication for lupus, and it will start with this drug."

Stump, the drug development chief hoping for that positive first PowerPoint slide, said: "Heaven knows these patients need something different." Everyone will know soon.

The Double-Edged Sword of Immunity

In response to infection, a healthy immune system produces antibodies—proteins that fight and destroy invading pathogens such as viruses, bacteria, and other foreign substances. But in lupus something goes awry with the chain of events leading to antibody production. As a result, the immune system produces "autoantibodies" against some of the body's own molecules, cells and tissues.

TLRs are proteins found in immune cells that normally help stimulate the initial response of the immune system to foreign pathogens. Humans have 10 different types of TLRs. Some of them sit on the surface of immune cells and seek out molecules that appear on the coating of bacteria and viruses. Other TLRs—TLR 3, TLR7, (TLR 8 in humans, but not mice), and TLR 9—reside inside immune cells, in a compartment known as the endolysosome, where bits of foreign substances usually end up.

When bacteria or viruses enter the body, some are engulfed by immune cells and degraded in the endolysosome. Inside this compartment, resident TLRs come across the bacterial and viral debris. These TLRs specifically detect the genetic material of pathogens—viral DNA, viral RNA, and bacterial DNA—and stimulate immune cells to produce antibodies against these molecules.

But the production of antibodies against foreign DNA and RNA seems to be particularly prone to error. The most common types of autoantibodies found in lupus patients are ones to the body's own genetic material—the DNA and RNA that resides inside the cell's command center, or nucleus. As a result, doctors often test for the presence of "antinuclear" antibodies to diagnose lupus.

"That's the Achilles heel," says Kono. "These endolysosomal TLRs are needed for viral and bacterial immunity, but they open the possibility of self reactivity."

Toll-Like Receptors and Lupus

Scientists don't quite know how antinuclear antibodies develop, but have suspected for some time that TLRs might be involved. By engineering mice that lack either TLR 7 or TLR9, scientists have gathered evidence that these TLRs may play a role in the disease.

"Earlier studies had strongly suggested that endolysosomal TLRs were important, but if you eliminate one or the other you do not get a huge effect," says Kono. "So we asked, 'What happens if you get rid of all the endolysosomal nucleic acid-sensing TLRs at once?'"

To answer this question, Kono and colleagues took advantage of strains of laboratory mice prone to lupus. These mice spontaneously develop many of the same signs and symptoms as humans with the disease. The next step was to eliminate TLR 3, TLR 7, and TLR 9 in these lupus-prone mice.

But how do you get rid of three proteins at once? Kono and colleagues knew that these TLRs need to be transported to the endolysosome to function. They also knew that one particular protein, called UNC-93B, produced by a gene called Unc93b1, serves as an essential "taxi" service. The UNC-93B protein attaches itself to TLR 3, TLR 7, and TLR 9 and facilitates their transport from the compartment in the cell where they are made to the endolysosome.

Using geneticists' tools of the trade, Kono and colleagues, engineered lupus-prone mice with an inactive Unc93b1 gene. Compared to lupus-prone mice with a functioning Unc93b1 gene, the mice with the Unc93b1 mutation produced fewer antinuclear antibodies and had fewer and less severe symptoms of lupus.

As a further test, Kono and colleagues treated the mutant mice with a substance that stimulates TLR 4—as TLR 4 stimulation is known to promote the production of autoantibodies. But even with TLR 4 stimulation, the mice lacking functioning TLR 3, TLR 7, and TLR 9 did not develop lupus.

"It seems like these three TLRs are absolutely required for optimal autoantibody production," says Kono. "This is an important finding that builds on results obtained by other groups."

The results "suggest that the three endosomal TLRs, or UNC-93B itself, might be good targets for therapy," says Kono, adding that more tests will be needed before these findings are translated into treatments for patients. "We are definitely getting closer to understanding the etiology of this autoimmune disease."

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In addition to Kono, other co-authors of the article "Endosomal TLR signaling is required for anti-nucleic acid and rheumatoid factor autoantibodies in lupus," include M. Katarina Haraldsson, Brian R. Lawson, K. Michael Pollard, Yi Ting Koh, Xin Du, Carrie N. Arnold, Roberto Baccala, Bruce Beutler, and Argyrios N. Theofilopoulos of The Scripps Research Institute, and Gregg J. Silverman of the University of California, San Diego.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California with a second campus located in Jupiter, Florida. Research at Scripps Florida focuses on basic biomedical science, drug discovery, and technology development.

HGS and GlaxoSmithKline (GSK) have agreed terms to develop and sell belimumab, formerly LymphoStat-B and now known under the brand name Benlysta. Under the agreement HGS will conduct the phase 3 trial, with help from GSK.

Lupus is an autoimmune disease that affects mainly women in their childbearing years. The immune system attacks the patient's own body and tissue, causing inflammation at the site of the attack, which varies from person to person.

Estimates suggest there are 5 million people worldwide living with various forms of lupus, including SLE, 1.5 million of them in the US. For many people with lupus it is little more than a nuisance, but for some it is life-threatening.

Symptoms of lupus vary, depending on which part of the body is affected, for instance it could be a rash if the skin is attacked, or joint pain if the joints are attacked. For this reason lupus often mimics other diseases such as multiple sclerosis and rheumatoid arthritis and can be very difficult to diagnose. There is no single definitive test of the disease and accurate diagnosis relies on a number of factors, including symptoms and history.

There are two types of lupus: discoid, which affects only the skin, and the other is systemic (full name systemic lupus erythematosus, SLE), which affects the skin, joints and often internal organs such as the heart and/or kidneys. Belimumab, the drug tested in this trial, is designed to treat the second type, SLE.

Dr Joan T Merrill, a study investigator, Program Chair, Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, and Professor, Department of Medicine, University of Oklahoma Health Sciences Center, said that the results presented at EULAR 2009 suggest:

"The apparent durability of clinical effect and the favorable safety profile observed for belimumab suggest that belimumab has the potential to become an important new treatment for patients with SLE."

HGS Vice President, Clinical Research - Immunology, Rheumatology and Infectious Diseases, Dr William W Freimuth, said they were encouraged by the results and the safety data presented at the meeting.

"The incidence rates per 100 patient years of all adverse event categories, including serious adverse events, overall adverse events, and serious infections were similar for belimumab and placebo during the 52-week double-blind period, and remained the same or decreased over four years of continuous treatment," said Freimuth.

Depending on how well Benlysta (belimumab) performs in the phase 3 trial, the drug could "represent a significant advance in the treatment of SLE", he added.

The phase 3 data for Benlysta will appear in July 2009 from the BLISS-52 trial, and in November 2009 from the BLISS-76 trial. Both these trials are the largest clinical trials ever conducted in lupus patients, said HGS in a press statement.

Benlysta (belimumab) is a human monoclonal antibody that selectively targets and inhibits the B-lymphocyte stimulator (BLyS), a naturally occurring protein discovered by HGS. The protein plays an important role in turning B-lymphocyte cells into mature plasma B cells, which produce antibodies, the immune system's first line of defence against infection (the "foot soldiers" of the immune system).

Higher than normal levels of BLyS produce too many antibodies, which appears to correlate with the severity of disease in lupus and other autoimmune illnesses.

"Preclinical and clinical studies demonstrate that BLyS antagonists can reduce autoantibody levels and help control autoimmune disease activity," said the HGS statement, which stated that the trial data presented at the EULAR 2009 meeting showed:
Continued treatment with Benlysta (belimumab) was associated with "sustained improvement or stabilization of SLE disease activity and with decreased frequency of SLE disease flares in serologically active patients through four years of treatment".

The overall incidence of adverse events, serious or otherwise, infections and malignancies, including lab abnormalities either decreased or stabilized from week 52 to week 208 of the trial.

Increase from 46 to 57 per cent in the response rate that was chosen as the primary endpoint of the phase 3 trial. This was a cluster of measures, including:" improvement in SELENA SLEDAI score of 4 points or more, no BILAG worsening, and no worsening in Physician's Global Assessment; post hoc; intention-to-treat analysis".

Decrease from 62 to 16 per cent in the overall frequency of SLE flares, as measured by the SELENA SLEDAI Flare Index.

Plus a decrease from 8 to 1 per cent in frequency of severe flares.

Decrease from 23 to 5 per cent in frequency of patients having one new BILAG A organ domain score, or more than one new BILAG B organ domain score (BILAG A indicates a severe flare, while B indicates a moderate flare due to lupus disease).
For the trial, which evaluated the effectiveness and safety of Benlysta (belimumab) plus standard care against placebo plus standard care, a total of 449 SLE patients were randomly assigned to have either one of three different doses of the active drug or placebo over 52 weeks.

At the end of 52 weeks, 345 of the patients chose to continue in an optional 24 week extension, during which all patients received the active drug. At the end of 76 weeks, 296 patients chose to continue with belimumab in an "open-label long-term continuation phase" where all patients were given the same dose. The current situation, as of 1 June 2009, is that 213 patients are still receiving treatment in the continuation study, said HGS.

Petar Lenert, from the University of Iowa, worked with a team of researchers to develop and test the compounds. He said, "The increased potency of class R INH-ODNs for certain cells involved in lupus flare-ups will help patients by providing specific inhibition, yet allowing them to generate a protective immune response when needed".

Lenert and his colleagues found that their INH-ODN drugs, composed of double-stranded DNA-like analogues carrying autoimmune-inhibitory sequences, were able to selectively reduce the activity of autoreactive B cells and dendritic cells. When given to mice with lupus, the compounds delayed death and reduced kidney damage.

Systemic lupus erythematosus, more commonly known simply as lupus, is thought to affect around a million people in the USA, but prevalence varies by country and ethnicity. It is much more common in women than men and there is currently no known cure. During periodic 'flares', the immune system of people with the condition mounts an attack on cells and tissues throughout the body, resulting in a range of symptoms including the characteristic 'butterfly rash' across the cheeks. With further testing, Lenert and his colleagues hope that class R INH-ODNs may become another weapon in the fight against the disease.

DNA-like class R inhibitory oligonucleotides (INH-ODNs) preferentially block autoantigen-induced B-cell and dendritic cell activation in vitro and autoantibody production in lupus-prone MRL-Fas lpr/lpr mice in vivo
Petar Lenert, Kei Yasuda, Liliana Busconi, Patrice Nelson, Courtney Fleenor, Radhika S Ratnabalasuriar, Peter L Nagy, Robert F Ashman, Ian R Rifkin and Ann Marshak-Rothstein
Arthritis Research & Therapy http://arthritis-research.com/