2001 Central Nervous System
Some ten years ago, scientist Dr. Betty Diamond came to the Lupus Research Institute with a critical clinical question that could only be answered with molecular research – why do four out of five people with lupus suffer with some type of neuropsychiatric difficulty? With funding granted on the merit of her hypothesis, Dr. Diamond found her answer. Based on that research, she is now developing a novel drug-like molecule that could lead to a treatment for lupus.
Dr. Diamond’s original LRI-supported research discovery found that a particular type of lupus antibody found in the brains of lupus patients can attach to and kill nerve cells in the brain, causing neurological and cognitive difficulties. Dr. Diamond, together with Dr. Yousef Al-Abed and other colleagues at the Feinstein Institute of Medical Research in New York, recently published a paper in the Proceedings of the National Academy of Sciences describing how their new molecule neutralizes (counteracts) the specific type of nerve-damaging lupus autoantibody she had identified years before. In this recent study, the new molecule protected brain cells in mice from damage by lupus autoantibodies.
“The LRI was the first organization to fund studies of this model of neuropsychiatric lupus,” said Dr. Diamond. “With the Institute’s grant as well as subsequent funding from the NIH, we provided the first molecular explanation of how the central nervous system is attacked in lupus. We are even more excited to have now developed a molecule that can block that attack.”
Potential for Patients
Like any breakthrough, this discovery did not happen in a vacuum. Other research teams have been able to neutralize the autoantibodies Dr. Diamond originally identified by using a peptide (a short chain of amino acids) that mimics the receptor the autoantibodies bind to. But its potential as a treatment is limited because the peptide cannot be taken orally and can inadvertently activate the immune system. Dr. Diamond’s group designed their new molecule with a similar shape as the earlier peptide, but to overcome its limitations, used distinct chemical building blocks so that the molecule can be absorbed orally and avoid triggering the immune system.
The Feinstein researchers stress that the molecule is still at an early stage of drug development. They will share a $571,610 NIH grant with Biomedical Research Models Inc. to test the molecule to see if it is safe for clinical trials with patients.
Cognition and immunity; antibody impairs memory. Immunity. 2004 Aug;21(2):179-88. Kowal C, DeGiorgio LA, Nakaoka T, Hetherington H, Huerta PT, Diamond B, Volpe BT.
Immunity and behavior: antibodies alter emotion. Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):678-83. Huerta PT, Kowal C, DeGiorgio LA, Volpe BT, Diamond B.
Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors. Eur J Neurol. 2005 May;12(5):392-8. Omdal R, Brokstad K, Waterloo K, Koldingsnes W, Jonsson R, Mellgren SI.
Autoantibodies to a NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus. Ann Rheum Dis. 2005 Aug;64(8):1210-3. Husebye ES, Sthoeger ZM, Dayan M, Zinger H, Elbirt D, Levite M, Mozes E.
Generation of a unique small molecule peptidomimetic that neutralizes lupus autoantibody activity. Bloom O, Cheng KF, He M, Papatheodorou A, Volpe BT, Diamond B, Al-Abed Y. Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10255-9. Epub 2011 Jun 6.
Dr. Diamond won a $6.5 million program grant from the NIH to build on more strategies for dealing with this devastating lupus-related development.
Rev. March 2012