The Search for Answers to Lupus: How  You  Can Get Involved Meggan Mackay, MD, MS Bronx-Lebanon Hospital Center Bronx, New...
Systemic Lupus Erythematosus Le Loup :   “The Wolf”
Lupus <ul><li>A chronic   autoimmune  disease that can cause inflammation and injury in different parts of the body, most ...
Lupus
Lupus
fatigue depression memory thief Lupus                                                        
Signs and Symptoms <ul><li>    Symptoms Occurrence    </li></ul><ul><li>Achy joints (arthralgias)    95%  </li></ul><ul><l...
Important Questions in Lupus <ul><li>What causes lupus? </li></ul><ul><li>Why are women, especially women of color, more a...
Lupus: Current Treatment Options <ul><li>Hydroxychloroquine/ Plaquenil </li></ul><ul><li>Steroids </li></ul><ul><li>Azathi...
Belimumab Buzz   ! “  Lupus drug belimumab (Benlysta) data highly promising:  GSK, Human Genome Sciences” “ No new drug fo...
&quot;I Have Lupus, Lupus Does  NOT   Have Me!&quot;
Research in Lupus <ul><li>The more that is known about clinical outcomes and immune abnormalities associated with lupus, t...
Clinical  Research:   Patient   Oriented Research Observational  Studies Interventional : Clinical  Trials Translational  ...
Observational  Studies Looking for Clues… <ul><li>No Medications! </li></ul><ul><li>Many Purposes: </li></ul><ul><li>Natur...
Observational  Studies Looking for Clues… <ul><li>Cohorts of subjects (groups of patients) that agree to participate </li>...
Observational  Studies Looking for Clues… <ul><li>Question:  </li></ul><ul><li>Are autoantibodies present before the onset...
Antibodies <ul><li>Antibodies are proteins made by activated B cells in the immune system to help fight infections </li></ul>
Autoantibodies <ul><li>ANA: </li></ul><ul><li>Antinuclear antibodies (ANAs) are directed against parts of the cell nucleus...
Observational  Studies Looking for Clues… Development of Autoantibodies Before the Clinical Onset of Systemic Lupus Erythe...
Observational  Studies Looking for Clues… Development of Autoantibodies Before the Clinical Onset of Systemic Lupus Erythe...
Correlation of vitamin D with SLEDAI score (disease activity) Observational  Studies Looking for Clues… p=.026 Mean SLEDAI...
Translational  Studies <ul><li>Taking bench science to the bedside in search of  mechanisms  of disease… </li></ul><ul><li...
Translational  Studies Mechanisms of Disease… <ul><li>Differences between patients  </li></ul><ul><li>and healthy individu...
Translational   Studies Mechanisms of Disease… <ul><li>Example:  Prospective study of inhibitory FcIIb receptors on B cell...
Figure 2.  Expression of  Fc γ RIIB   on naïve and memory B cells in normals vs SLE Naïve B Cells ( p =NS) Normal SLE Figu...
Translational  Studies Mechanisms of Disease…  
Correlation of vitamin D with SLEDAI score (disease activity) Observational  Studies Looking for Clues… p=.026 Mean SLEDAI...
Translational   Studies Mechanisms of Disease… Addition of  vitamin D   to lupus plasma inhibits transfer of the interfero...
Translational  Studies Mechanisms of Disease… <ul><li>The interferon signature in blood cells is inhibited after one month...
<ul><li>Translational  Studies Mechanisms of Disease… </li></ul><ul><li>Unraveling the mystery of cognitive dysfunction in...
Cognitive Dysfunction <ul><li>The most common form of brain involvement in lupus; 50-80% of patients affected </li></ul>As...
Cognitive Dysfunction <ul><li>Why do brain cells die in lupus patients? </li></ul><ul><li>Autoantibody Associations: </li>...
Brain Cell Death/anti-NR2 Antibodies <ul><li>Anti-NR2 antibodies are found in 50% of patients and have been eluted from SL...
Brain Damage by Lupus  Antibody in Mice Control antibody Cresyl violet Neu -N Lupus  antibody
Neural Compensation for Damage Sternberg 1 object/retention phase Disease > 10 years Disease <2 years
Clinical Trials <ul><li>What are they? </li></ul><ul><li>Very carefully controlled human studies of drugs that are not yet...
Clinical Trials <ul><li>Expectation :   Drug A will be very effective in treating kidney disease in lupus </li></ul><ul><l...
Clinical Trials <ul><li>150 Lupus Patients with Active Kidney Disease </li></ul><ul><li>75 to Receive  Drug A   75 to Rece...
Clinical Trials <ul><li>Important Things to Know: </li></ul><ul><li>All drugs have been tested in many animal models befor...
Clinical Trials <ul><li>Each  Clinical Trial  is designed to answer a specific question therefore: </li></ul><ul><li>Only ...
Clinical Trials <ul><li>“ But….aren’t I still being used as a  guinea pig ?” </li></ul>
The Search for Answers to Lupus: You’re   participation makes a BIG difference! Remember,
&quot;I Have Lupus,  Lupus Does  NOT  Have Me!&quot;
Thank You!
Upcoming SlideShare
Loading in …5
×

Clinical Research In Lupus by Dr. Meggan Mackay

2,753 views
2,597 views

Published on

Published in: Health & Medicine, Business
0 Comments
4 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
2,753
On SlideShare
0
From Embeds
0
Number of Embeds
11
Actions
Shares
0
Downloads
0
Comments
0
Likes
4
Embeds 0
No embeds

No notes for slide

Clinical Research In Lupus by Dr. Meggan Mackay

  1. 1. The Search for Answers to Lupus: How You Can Get Involved Meggan Mackay, MD, MS Bronx-Lebanon Hospital Center Bronx, New York
  2. 2. Systemic Lupus Erythematosus Le Loup : “The Wolf”
  3. 3. Lupus <ul><li>A chronic autoimmune disease that can cause inflammation and injury in different parts of the body, most commonly the skin, joints and kidneys. Lupus can be a mild disease, a severe and life-threatening illness or anything in-between. </li></ul>
  4. 4. Lupus
  5. 5. Lupus
  6. 6. fatigue depression memory thief Lupus                                                        
  7. 7. Signs and Symptoms <ul><li>    Symptoms Occurrence    </li></ul><ul><li>Achy joints (arthralgias)   95%  </li></ul><ul><li>Fever more than 100 degrees F (38 degrees C)   90%  </li></ul><ul><li>Arthritis (swollen joints)   90%  </li></ul><ul><li>Prolonged or extreme fatigue    81%  </li></ul><ul><li>Skin Rashes    74%  </li></ul><ul><li>Anemia    71%   </li></ul><ul><li>Kidney Involvement    50%  </li></ul><ul><li>Pain in the chest on deep breathing (pleurisy)    45%   </li></ul><ul><li>Butterfly-shaped rash across the cheeks and nose    42%   </li></ul><ul><li>Sun or light sensitivity (photosensitivity)    30%  </li></ul><ul><li>Hair loss    27%   </li></ul><ul><li>Abnormal blood clotting problems    20%  </li></ul><ul><li>Raynaud's phenomenon (fingers turning white   and/or blue in the cold)    17%   </li></ul><ul><li>Seizures    15%   </li></ul><ul><li>Mouth or nose ulcers    12% </li></ul>
  8. 8. Important Questions in Lupus <ul><li>What causes lupus? </li></ul><ul><li>Why are women, especially women of color, more affected? </li></ul><ul><li>What makes the disease flare? </li></ul><ul><li>Why do some patients have more severe disease than others? </li></ul><ul><li>Can we make better medications for lupus? </li></ul><ul><li>Can we prevent lupus? </li></ul><ul><li>Can we cure lupus? </li></ul>
  9. 9. Lupus: Current Treatment Options <ul><li>Hydroxychloroquine/ Plaquenil </li></ul><ul><li>Steroids </li></ul><ul><li>Azathioprine/ Imuran </li></ul><ul><li>Methotrexate </li></ul><ul><li>Cellcept </li></ul><ul><li>Arava </li></ul><ul><li>Cyclophosphamide </li></ul>
  10. 10. Belimumab Buzz ! “ Lupus drug belimumab (Benlysta) data highly promising: GSK, Human Genome Sciences” “ No new drug for lupus has been approved in more than 50 years”
  11. 11. &quot;I Have Lupus, Lupus Does NOT Have Me!&quot;
  12. 12. Research in Lupus <ul><li>The more that is known about clinical outcomes and immune abnormalities associated with lupus, the better equipped we are to fight the disease! </li></ul>
  13. 13. Clinical Research: Patient Oriented Research Observational Studies Interventional : Clinical Trials Translational Studies
  14. 14. Observational Studies Looking for Clues… <ul><li>No Medications! </li></ul><ul><li>Many Purposes: </li></ul><ul><li>Natural course of the disease </li></ul><ul><li>Effects of gender, age, ethnicity and environmental influences on disease outcomes </li></ul><ul><li>Effects of gender, age, ethnicity and environmental influences on disease susceptibility </li></ul>
  15. 15. Observational Studies Looking for Clues… <ul><li>Cohorts of subjects (groups of patients) that agree to participate </li></ul><ul><li>Observational studies may not give definite answers to specific questions </li></ul><ul><li>however </li></ul><ul><li>many hypotheses are generated from observational studies </li></ul>
  16. 16. Observational Studies Looking for Clues… <ul><li>Question: </li></ul><ul><li>Are autoantibodies present before the onset of lupus? </li></ul>
  17. 17. Antibodies <ul><li>Antibodies are proteins made by activated B cells in the immune system to help fight infections </li></ul>
  18. 18. Autoantibodies <ul><li>ANA: </li></ul><ul><li>Antinuclear antibodies (ANAs) are directed against parts of the cell nucleus </li></ul><ul><li>Found in more than 95% of patients with lupus </li></ul><ul><li>Most lupus patients also have other autoantibodies directed against different cells in the body </li></ul>
  19. 19. Observational Studies Looking for Clues… Development of Autoantibodies Before the Clinical Onset of Systemic Lupus Erythematosus Arbuckle et al, NEJM 2003
  20. 20. Observational Studies Looking for Clues… Development of Autoantibodies Before the Clinical Onset of Systemic Lupus Erythematosus Arbuckle et al, NEJM 2003
  21. 21. Correlation of vitamin D with SLEDAI score (disease activity) Observational Studies Looking for Clues… p=.026 Mean SLEDAI scores 0 1 2 3 4 5 6 7 25-D<=10 25-D>10 n=40 n=125 SLEDAI score
  22. 22. Translational Studies <ul><li>Taking bench science to the bedside in search of mechanisms of disease… </li></ul><ul><li>“ To study the phenomenon of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” </li></ul><ul><li>William Osler </li></ul>
  23. 23. Translational Studies Mechanisms of Disease… <ul><li>Differences between patients </li></ul><ul><li>and healthy individuals on a </li></ul><ul><li>molecular level </li></ul><ul><li>Differences in the immune </li></ul><ul><li>system between patients in remission and patients with active disease </li></ul><ul><li>Predictors of disease flares </li></ul>
  24. 24. Translational Studies Mechanisms of Disease… <ul><li>Example: Prospective study of inhibitory FcIIb receptors on B cells in lupus patients to identify: </li></ul><ul><li>Associations with demographic data </li></ul><ul><li>Associations with disease activity </li></ul><ul><li>Associations with medication use </li></ul>
  25. 25. Figure 2. Expression of Fc γ RIIB on naïve and memory B cells in normals vs SLE Naïve B Cells ( p =NS) Normal SLE Figure 2A Normal SLE Figure 2B Memory B Cells ( p <0.001) MFI MFI
  26. 26. Translational Studies Mechanisms of Disease…  
  27. 27. Correlation of vitamin D with SLEDAI score (disease activity) Observational Studies Looking for Clues… p=.026 Mean SLEDAI scores 0 1 2 3 4 5 6 7 25-D<=10 25-D>10 n=40 n=125 SLEDAI score
  28. 28. Translational Studies Mechanisms of Disease… Addition of vitamin D to lupus plasma inhibits transfer of the interferon signature to normal blood cells
  29. 29. Translational Studies Mechanisms of Disease… <ul><li>The interferon signature in blood cells is inhibited after one month of vitamin D replacement therapy in 3 lupus patients </li></ul>Interferon inducible genes before and after Vitamin D
  30. 30. <ul><li>Translational Studies Mechanisms of Disease… </li></ul><ul><li>Unraveling the mystery of cognitive dysfunction in lupus: </li></ul><ul><li>Memory Word </li></ul><ul><li> Finding </li></ul><ul><li>Concentration </li></ul>
  31. 31. Cognitive Dysfunction <ul><li>The most common form of brain involvement in lupus; 50-80% of patients affected </li></ul>Associated with brain shrinkage suggesting that brain cells may be dying
  32. 32. Cognitive Dysfunction <ul><li>Why do brain cells die in lupus patients? </li></ul><ul><li>Autoantibody Associations: </li></ul><ul><li>Antiphospholipid antibody </li></ul><ul><li>Anti-ribosomal P antibody </li></ul><ul><li>Anti-neuronal antibody </li></ul><ul><li>Anti-NR2 antibody </li></ul><ul><li>Cytokines released by </li></ul><ul><li>cells in the brain </li></ul>I have to squeeze my brain really hard to get a thought out!
  33. 33. Brain Cell Death/anti-NR2 Antibodies <ul><li>Anti-NR2 antibodies are found in 50% of patients and have been eluted from SLE brain tissue </li></ul><ul><li>They can bind to brain cells and kill them </li></ul><ul><li>Normal mice injected with these antibodies end up with a “shrinking brain” and have abnormal memory and </li></ul><ul><li>fear responses </li></ul>
  34. 34. Brain Damage by Lupus Antibody in Mice Control antibody Cresyl violet Neu -N Lupus antibody
  35. 35. Neural Compensation for Damage Sternberg 1 object/retention phase Disease > 10 years Disease <2 years
  36. 36. Clinical Trials <ul><li>What are they? </li></ul><ul><li>Very carefully controlled human studies of drugs that are not yet approved by the U.S. Food and Drug Administration (FDA) for use in a particular disease. </li></ul><ul><li>The FDA will approve a drug once it has been proven that the benefits of the drug outweigh the risks. </li></ul>
  37. 37. Clinical Trials <ul><li>Expectation : Drug A will be very effective in treating kidney disease in lupus </li></ul><ul><li>Problem : How do we prove this? </li></ul>
  38. 38. Clinical Trials <ul><li>150 Lupus Patients with Active Kidney Disease </li></ul><ul><li>75 to Receive Drug A 75 to Receive Placebo </li></ul><ul><li>Plus regular therapy Plus regular therapy </li></ul>Which Group has a better outcome?
  39. 39. Clinical Trials <ul><li>Important Things to Know: </li></ul><ul><li>All drugs have been tested in many animal models before human studies </li></ul><ul><li>All patients entering into clinical trials are volunteers </li></ul><ul><li>All patients entering into clinical trials have signed an informed consent meaning that ALL of the possible risks have been explained to them </li></ul><ul><li>All clinical trials are designed so that the patient’s safety is the primary concern </li></ul>
  40. 40. Clinical Trials <ul><li>Each Clinical Trial is designed to answer a specific question therefore: </li></ul><ul><li>Only eligible patients are accepted into each study </li></ul><ul><li>Entering a clinical trial requires a commitment from the patient as well as the investigator </li></ul><ul><li>You should always speak with your primary Rheumatologist before deciding to enter a clinical trial </li></ul>
  41. 41. Clinical Trials <ul><li>“ But….aren’t I still being used as a guinea pig ?” </li></ul>
  42. 42. The Search for Answers to Lupus: You’re participation makes a BIG difference! Remember,
  43. 43. &quot;I Have Lupus, Lupus Does NOT Have Me!&quot;
  44. 44. Thank You!

×