New Haven, Conn. — Yale University researchers were able to reduce symptoms of lupus in mice by eliminating a key immune system cell and in doing so may have identified a new therapeutic target for a variety of other autoimmune diseases.
The findings, reported in the December 16 issue of the journal Immunity, focused on the role the dendritic cell plays in systemic lupus erythematosus or SLE, a chronic inflammatory disease that affects a variety of parts of the body including skin, joints, blood and kidneys. Dendritic cells are important for initiating the immune response to pathogens but it is unclear what role they play in autoimmune diseases, such as SLE.
A team led by Mark Shlomchik, Professor of Laboratory Medicine and of Immunobiology and senior author of the paper, knocked out dendritic cells in lupus-prone mice and found a dramatic reduction in symptoms of lupus. They also discovered another surprise.
Dendritic cells were believed to be crucial in activating T cells, which along with B cells comprise the two main arms of the immune system. However, knocking out the dendritic cells in lupus mice did not reduce the activation of pathogenic T cells as expected. Instead, the cells disappeared from inflamed tissue such as kidneys, causing a reduction in symptoms in lupus mice lacking the dendritic cells. Dendritic cells appear to play a localized role in lupus tissue damage and so might make a good therapeutic target for lupus and possibly other autoimmune diseases as well, the authors say.
“Dendritic cells could be having the same effects in a variety of other autoimmune diseases, but we will not know until we do similar experiments in other disease models,” Shlomchik said.
Other Yale authors of the paper are Lino Teichmann, Michael Kashgarian, and Michelle Harris-Ols.
The work was funded by the National Institute of Arthritis and Musculoskeletal Diseases and the Lupus Research Institute.
http://insciences.org/article.php?article_id=9737
Thursday, December 16, 2010
Tuesday, November 16, 2010
FDA recommends new Lupus drug for approval!
[from WSJ:]
A Food and Drug Administration panel of outside experts recommended Tuesday that the agency approve lupus drug Benlysta, developed by Human Genome Sciences Inc. and GlaxoSmithKline PLC.
The 13-to-2 vote increases the likelihood of the drug getting to patients with the autoimmune disease, making it the first new treatment in more than 50 years. The panel also voted that the data surrounding the drug demonstrated its effectiveness and its safety.
Lupus has historically been a difficult development area for drug makers, partly because of the varied nature of its symptoms make it hard to prove a treatment is effective in a large-scale clinical trial. Attempts to develop new treatments for the condition have created a long list of failures.
Benlysta is important for both companies as it one of the most important new drugs in Glaxo's pipeline and Human Genome Sciences has no products on the market.
Leerink Swann & Co. analysts project that global sales of Benlysta could exceed $5 billion in 2020. The drug's success in two large studies, called Bliss, has produced consistent speculation that Glaxo, or another large drug maker, would acquire Human Genome.
Lupus occurs when the body attacks itself, causing inflammation and tissue damage virtually anywhere in the body, making it both difficult to diagnose and treat. It affects about 1.5 million people nationally, according to the Lupus Foundation of America.
Benlysta is designed to help relieve lupus symptoms that can include joint pain and swelling resembling severe arthritis as well as rashes and inflammation of the kidneys. It blocks a protein required for the development of certain immune system cells thought to play a key role in lupus.
If Benlysta is approved, its label will likely include strong warnings, as many drugs for rheumatoid arthritis already do. After voting on the approval, many panel members urged that the label of the drug should note that the drug hasn't been tested in certain populations, including those with severe kidney disease.
On Tuesday, researchers who worked with the companies presented data from large clinical trials that they said showed the drug was effective.
After failing earlier testing, the companies worked with the FDA to design the trials with a never-used combination of several disease-activity measures, including the drug's effect on recurring flare-ups and on symptom severity.
At the meeting, numerous lupus patients testified about their experiences with the disease including constant fatigue, crippling pain and respiratory problems that required lengthy, repeated hospitalization. They expressed frustration with the lack of effective therapies and urged the FDA to approve Benlysta.
Some patients--many of whose travel expenses were reimbursed by the companies--talked about their positive experiences with the drug in clinical trials. Most of the patients who testified were women or teenage girls; lupus largely targets females of child-bearing age.
Because the disease can cause various symptoms, physicians traditionally use different treatments, including anti-inflammatory drugs, steroids, antimalarials and immunosuppressants, all of which have their own potential side effects.
FDA staff scientists also testified and reiterated concerns expressed in an analysis released Friday that associated the drug with an increase in death, and serious side effects including infections and adverse psychiatric events.
Panel member David Blumenthal, assistant professor of medicine at Case Western Reserve University, strongly questioned the presentation of clinical data for Benlysta. The first study, called Bliss-52, only included patients in Asia, Latin America and Eastern Europe, and therefore wasn't representative of lupus patients in the U.S., he said.
The second study, Bliss-76, used patients from the U.S. and Western Europe and showed less effectiveness results than the previous trial after a year. A six-month follow-up showed that some benefits of the drug declined.
Several panel members reiterated Dr. Blumenthal's doubts about the strength of that data. Panel members and the FDA representative expressed concerns that the drug appeared less effective or perhaps even harmful in certain subgroups including African-Americans. Agency scientists also noted that African-American patients' symptoms seemed to worsen on Benlysta. That is particularly troublesome because African-Americans generally have a more aggressive form of lupus, the FDA memo said.
A company-affiliated researcher said at Tuesday's meeting that the results in African-Americans were disappointing and needed to be addressed in future research.
Rheumatologist Murray Urowitz of the University of Toronto told the panel that several factors, including lupus patients' continued use of the steroid prednisone during Bliss tests, make doing any clinical trials on lupus "daunting."
But Dr. Urowitz, who participated in the companies' Benlysta research, added that results from clinical trials indicate good efficacy compared to placebos in relieving some symptoms.
The president of the Lupus Foundation of America, Sandra Raymond, told the advisory committee that patients need new drugs that will improve their quality of life, and recommended Benysta's approval. The foundation, like several lupus groups that urged FDA approval, receives donations from the drug industry.
A Food and Drug Administration panel of outside experts recommended Tuesday that the agency approve lupus drug Benlysta, developed by Human Genome Sciences Inc. and GlaxoSmithKline PLC.
The 13-to-2 vote increases the likelihood of the drug getting to patients with the autoimmune disease, making it the first new treatment in more than 50 years. The panel also voted that the data surrounding the drug demonstrated its effectiveness and its safety.
Lupus has historically been a difficult development area for drug makers, partly because of the varied nature of its symptoms make it hard to prove a treatment is effective in a large-scale clinical trial. Attempts to develop new treatments for the condition have created a long list of failures.
Benlysta is important for both companies as it one of the most important new drugs in Glaxo's pipeline and Human Genome Sciences has no products on the market.
Leerink Swann & Co. analysts project that global sales of Benlysta could exceed $5 billion in 2020. The drug's success in two large studies, called Bliss, has produced consistent speculation that Glaxo, or another large drug maker, would acquire Human Genome.
Lupus occurs when the body attacks itself, causing inflammation and tissue damage virtually anywhere in the body, making it both difficult to diagnose and treat. It affects about 1.5 million people nationally, according to the Lupus Foundation of America.
Benlysta is designed to help relieve lupus symptoms that can include joint pain and swelling resembling severe arthritis as well as rashes and inflammation of the kidneys. It blocks a protein required for the development of certain immune system cells thought to play a key role in lupus.
If Benlysta is approved, its label will likely include strong warnings, as many drugs for rheumatoid arthritis already do. After voting on the approval, many panel members urged that the label of the drug should note that the drug hasn't been tested in certain populations, including those with severe kidney disease.
On Tuesday, researchers who worked with the companies presented data from large clinical trials that they said showed the drug was effective.
After failing earlier testing, the companies worked with the FDA to design the trials with a never-used combination of several disease-activity measures, including the drug's effect on recurring flare-ups and on symptom severity.
At the meeting, numerous lupus patients testified about their experiences with the disease including constant fatigue, crippling pain and respiratory problems that required lengthy, repeated hospitalization. They expressed frustration with the lack of effective therapies and urged the FDA to approve Benlysta.
Some patients--many of whose travel expenses were reimbursed by the companies--talked about their positive experiences with the drug in clinical trials. Most of the patients who testified were women or teenage girls; lupus largely targets females of child-bearing age.
Because the disease can cause various symptoms, physicians traditionally use different treatments, including anti-inflammatory drugs, steroids, antimalarials and immunosuppressants, all of which have their own potential side effects.
FDA staff scientists also testified and reiterated concerns expressed in an analysis released Friday that associated the drug with an increase in death, and serious side effects including infections and adverse psychiatric events.
Panel member David Blumenthal, assistant professor of medicine at Case Western Reserve University, strongly questioned the presentation of clinical data for Benlysta. The first study, called Bliss-52, only included patients in Asia, Latin America and Eastern Europe, and therefore wasn't representative of lupus patients in the U.S., he said.
The second study, Bliss-76, used patients from the U.S. and Western Europe and showed less effectiveness results than the previous trial after a year. A six-month follow-up showed that some benefits of the drug declined.
Several panel members reiterated Dr. Blumenthal's doubts about the strength of that data. Panel members and the FDA representative expressed concerns that the drug appeared less effective or perhaps even harmful in certain subgroups including African-Americans. Agency scientists also noted that African-American patients' symptoms seemed to worsen on Benlysta. That is particularly troublesome because African-Americans generally have a more aggressive form of lupus, the FDA memo said.
A company-affiliated researcher said at Tuesday's meeting that the results in African-Americans were disappointing and needed to be addressed in future research.
Rheumatologist Murray Urowitz of the University of Toronto told the panel that several factors, including lupus patients' continued use of the steroid prednisone during Bliss tests, make doing any clinical trials on lupus "daunting."
But Dr. Urowitz, who participated in the companies' Benlysta research, added that results from clinical trials indicate good efficacy compared to placebos in relieving some symptoms.
The president of the Lupus Foundation of America, Sandra Raymond, told the advisory committee that patients need new drugs that will improve their quality of life, and recommended Benysta's approval. The foundation, like several lupus groups that urged FDA approval, receives donations from the drug industry.
Thursday, November 11, 2010
Stats
Finish time: 5:28:15
We raised: $3,000
Money raised by Team Life Without Lupus: over $130,000!
Thanks all :)
We raised: $3,000
Money raised by Team Life Without Lupus: over $130,000!
Thanks all :)
Tuesday, November 9, 2010
J's pictures
First Avenue
Reunited with my ski jacket and my boy.
And my girls.
My awesome gloves purchased at the expo.
Celebratory cake!
Monday, November 8, 2010
Marathon part 5: Manhattan, again
I missed the Harlem choir I'd heard about. Perhaps I was out of it? Or maybe they got tired before I got there. In any case, there was a lot of music and a flock of very enthusiastic kids handing out random food. I felt bad turning it all down, but was feeling some nausea from the exertion, three Nutrigrains ingested to get me that far and a half cup of Gatorade every mile.
I was very glad to have been warned that the first sight of trees is a park, but not the park. It's Marcus Garvey, and we ran around it to continue along Fifth Avenue. We headed down Fifth Avenue, but it was all up hill. Looooooong uphill. I knew it was long; I knew I'd be tired. I knew from Saturday exactly where than 24 mile mark was and I told myself to look ten feet in front of me and not to the top of the hill. Let the hill come to me, I love you hill, come to me hill. The crowds grew again. I listened to both the roar and a blasting ipod for power. I thought, this is as tough as it gets and I'm doing it. I was fine, and the truth is that I never doubted my ability to finish (saving severe migraine, ferry breakdown or other catastrophe). Am I "digging deep" now? Even at mile 23.8 after almost two miles of hill, I wasn't and I knew I wasn't. My feet hurt and it was not that easy to keep my legs going, but there was no wall, there were no cramps, and I've done harder.
I hit 90th Street, went into the park, hit the 24 mile mark, passed the Met at the top of a hill. I realized I was making it; it was basically the end. I suddenly remembered why I was running and thought about why I didn't feel like I was "digging deep". I had dug deep just to keep myself moving when I was stuck in a never ending and undiagnosed lupus flare, when I didn't have a lot of hope that that I'd be able to physically function like a "normal" person and have the energy to have "normal" person experiences without constant pain and be happy. This just wasn't as hard; I was in control.
On the way down the hill, I passed my parents, best friends and my person. I held it together, smiled and kept it light, but burst out crying thirty seconds later. Had I not been diagnosed and lucky enough to respond well to my life-quality-saving medication, I could've missed my out-of-this world college experience and these people that will always be my second family; and a third family from law school that I thought I'd been too lucky already to find and keep (even if by gchat). I could've missed the energy to jump into a train-distance relationship, move to Manhattan, make decisions fueled by ambition. I certainly would have missed the opportunity to see my people looking at me like they had no doubt I could run that far and my dad look at me at mile 24.5 without concern.
I pulled it together up the last hill to Central Park South. A spectator just to my left yelled "you can do it, Kate, you've got it, looking strong!" I rounded the corner and gradually picked up the pace along Central Park South. I smelled horse poop and wondered whether it really would have been that hard to clean the street for forty thousand people on their last legs. I hit Columbus circle, saw the glowing orange sun beginning to set between two buildings, and turned back into the park between a stage and some kind of metal structure with lighting equipment. I could see the mile 26 sign. I picked up the pace and people cheered louder, which I knew they would. I hit mile 26 and ran faster. They cheered louder and yelled things about a strong finish. The signs read "300 yards," "200 yards," and then I saw the finish line and the cameras. I smiled, pumped my arms harder, and sped across the line.
And burst out crying again. An old woman in a visor put the medal around my neck.
My feet hurt a lot at the end and I fell asleep at 8pm last night. Training was harder, and taking the leap to sign up was harder than that. Just going for it without knowing first that my body would cooperate was scary and not what cautious me was used to. This cause is obviously important to me, but it also ended up being an important lesson in how I should be thinking about pushing myself now, going for it without knowing it's a foregone conclusion.
So, a last thank you for contributing to the cause and encouraging me on this journey that has ended up meaning quite a lot to me.
[I'll post some pictures here as they become available so that you all can see my I'm-trying-to-look-cute/hot/tough/happy/relaxed awkward, sweaty smiles.]
I was very glad to have been warned that the first sight of trees is a park, but not the park. It's Marcus Garvey, and we ran around it to continue along Fifth Avenue. We headed down Fifth Avenue, but it was all up hill. Looooooong uphill. I knew it was long; I knew I'd be tired. I knew from Saturday exactly where than 24 mile mark was and I told myself to look ten feet in front of me and not to the top of the hill. Let the hill come to me, I love you hill, come to me hill. The crowds grew again. I listened to both the roar and a blasting ipod for power. I thought, this is as tough as it gets and I'm doing it. I was fine, and the truth is that I never doubted my ability to finish (saving severe migraine, ferry breakdown or other catastrophe). Am I "digging deep" now? Even at mile 23.8 after almost two miles of hill, I wasn't and I knew I wasn't. My feet hurt and it was not that easy to keep my legs going, but there was no wall, there were no cramps, and I've done harder.
I hit 90th Street, went into the park, hit the 24 mile mark, passed the Met at the top of a hill. I realized I was making it; it was basically the end. I suddenly remembered why I was running and thought about why I didn't feel like I was "digging deep". I had dug deep just to keep myself moving when I was stuck in a never ending and undiagnosed lupus flare, when I didn't have a lot of hope that that I'd be able to physically function like a "normal" person and have the energy to have "normal" person experiences without constant pain and be happy. This just wasn't as hard; I was in control.
On the way down the hill, I passed my parents, best friends and my person. I held it together, smiled and kept it light, but burst out crying thirty seconds later. Had I not been diagnosed and lucky enough to respond well to my life-quality-saving medication, I could've missed my out-of-this world college experience and these people that will always be my second family; and a third family from law school that I thought I'd been too lucky already to find and keep (even if by gchat). I could've missed the energy to jump into a train-distance relationship, move to Manhattan, make decisions fueled by ambition. I certainly would have missed the opportunity to see my people looking at me like they had no doubt I could run that far and my dad look at me at mile 24.5 without concern.
I pulled it together up the last hill to Central Park South. A spectator just to my left yelled "you can do it, Kate, you've got it, looking strong!" I rounded the corner and gradually picked up the pace along Central Park South. I smelled horse poop and wondered whether it really would have been that hard to clean the street for forty thousand people on their last legs. I hit Columbus circle, saw the glowing orange sun beginning to set between two buildings, and turned back into the park between a stage and some kind of metal structure with lighting equipment. I could see the mile 26 sign. I picked up the pace and people cheered louder, which I knew they would. I hit mile 26 and ran faster. They cheered louder and yelled things about a strong finish. The signs read "300 yards," "200 yards," and then I saw the finish line and the cameras. I smiled, pumped my arms harder, and sped across the line.
And burst out crying again. An old woman in a visor put the medal around my neck.
My feet hurt a lot at the end and I fell asleep at 8pm last night. Training was harder, and taking the leap to sign up was harder than that. Just going for it without knowing first that my body would cooperate was scary and not what cautious me was used to. This cause is obviously important to me, but it also ended up being an important lesson in how I should be thinking about pushing myself now, going for it without knowing it's a foregone conclusion.
So, a last thank you for contributing to the cause and encouraging me on this journey that has ended up meaning quite a lot to me.
[I'll post some pictures here as they become available so that you all can see my I'm-trying-to-look-cute/hot/tough/happy/relaxed awkward, sweaty smiles.]
Marathon part 4: Manhattan
Everyone knows that the marathon goes up First Avenue, and I knew that. Except that whenever I pictured arriving in Manhattan, in my head, we ran up Second. So, while I was excited to see the crowd I was hearing, exiting the bridge and making a left down to First Avenue just felt really wrong.
But the crowds, as promised, were terrific. They were loud and rowdy (helped, I'm sure, by the bars), reading and screaming my name like they knew me. I counted down block by block until 74th, a rising feeling of nervousness and excitment until I hit the people that actually knew me. Hugs, kisses and refusals of additional supplies. I was happy that I looked good enough that they wouldn't worry before they saw me again.
Up, up, up First Avenue to like 1,950th St.
Then another hill on a stupid little bridge, and back to people with signs!
"Welcome to the Bronx"
"Nice Legs!"
"Go Hotstuff!"
"Beer ===>"
"Your Feet Hurt Cause You're Kicking Ass"
"Who needs toenails? You have glory!"
Steel drumb band, booming something hard rock-y, and then a children's Asian drumming group in full uniform. We couldn't have been in the Bronx for more than twenty minutes to a half hour; in, a semi-circle, and back out. Then, a big hill of a bridge (I will forever notice that all bridges are hills) back to Manhattan.
Leaving the Bronx, there was more than one sign that read: "Run like you stole something."
But the crowds, as promised, were terrific. They were loud and rowdy (helped, I'm sure, by the bars), reading and screaming my name like they knew me. I counted down block by block until 74th, a rising feeling of nervousness and excitment until I hit the people that actually knew me. Hugs, kisses and refusals of additional supplies. I was happy that I looked good enough that they wouldn't worry before they saw me again.
Up, up, up First Avenue to like 1,950th St.
Then another hill on a stupid little bridge, and back to people with signs!
"Welcome to the Bronx"
"Nice Legs!"
"Go Hotstuff!"
"Beer ===>"
"Your Feet Hurt Cause You're Kicking Ass"
"Who needs toenails? You have glory!"
Steel drumb band, booming something hard rock-y, and then a children's Asian drumming group in full uniform. We couldn't have been in the Bronx for more than twenty minutes to a half hour; in, a semi-circle, and back out. Then, a big hill of a bridge (I will forever notice that all bridges are hills) back to Manhattan.
Leaving the Bronx, there was more than one sign that read: "Run like you stole something."
Marathon part 3: Queens
"Brooklyn Believes in YOU!" turned to "Queens Welcomes You!"
The Pulaski Bridge sucks. It's steep and the surroundings are 'eh'. We ran in a semi circle, I think, through some boring buildings in Queens, which felt annoyingly indirect and, compared to much of the course, unremarkable. But then I saw a beautiful sight, Scandals, my favorite strip club. Why? Location, location, location. I knew it meant I was approaching the onramp to the Queensboro Bridge. Everyone complains about it and a great many people walk up it (because it's a hill, but mostly, I think, because nobody is there to see), but I have never thought the Queensboro was that bad. Running to Manhattan and my waiting people made it mentally easier to stay running, and I took out the ipod for the first time. The song, "Wanna Be," was perfect for meeting my lover with my spice girl friends.
Approaching the end of the bridge, we could hear a loud roar.
[Next up: Manhattan]
The Pulaski Bridge sucks. It's steep and the surroundings are 'eh'. We ran in a semi circle, I think, through some boring buildings in Queens, which felt annoyingly indirect and, compared to much of the course, unremarkable. But then I saw a beautiful sight, Scandals, my favorite strip club. Why? Location, location, location. I knew it meant I was approaching the onramp to the Queensboro Bridge. Everyone complains about it and a great many people walk up it (because it's a hill, but mostly, I think, because nobody is there to see), but I have never thought the Queensboro was that bad. Running to Manhattan and my waiting people made it mentally easier to stay running, and I took out the ipod for the first time. The song, "Wanna Be," was perfect for meeting my lover with my spice girl friends.
Approaching the end of the bridge, we could hear a loud roar.
[Next up: Manhattan]
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