• CORRECTION: On Feb 27, 2015, this story was updated to correct the direction of pH change in T cells from mice with lupus symptoms. Lupus cells had lower pH levels.
Volume 93 Issue 8 | p. 7 | News of The Week
Issue Date: February 23, 2015 | Web Date: February 19, 2015

Drugs That Regulate Metabolism May Treat Lupus

Autoimmune Disease: Immune cells in mice with lupus symptoms have overactive metabolisms, study shows
Department: Science & Technology
News Channels: Biological SCENE
Keywords: lupus, autoimmune disease, T cells, metabolism, glycolysis, 2-deoxyglucose, metformin

In a patient with the autoimmune disease lupus, immune cells attack the body’s own tissues as if they were an invading pathogen. This can lead to damage to the skin, joints, kidneys, and even the brain.

Now a team of immunologists reports that some of these errant immune cells have an overactive metabolism, and that inhibiting two key metabolic pathways can reverse lupus symptoms in mice (Sci. Transl. Med. 2015, DOI: 10.1126/scitranslmed.aaa0835).

The study provides compelling evidence that a combination of metabolic inhibitors could be an effective lupus therapy, say Manan M. Mehta and Navdeep S. Chandel of Northwestern University in a perspective they wrote about the study.

Before testing these inhibitors, Laurence M. Morel at the University of Florida and her colleagues first studied the metabolism of CD4+ T cells. In lupus, the immune cells command B cells to produce ­autoantibodies, which target the body’s own tissue.

When T cells are on the hunt for pathogens, they ramp up their metabolism so they can proliferate quickly. Morel hypothesized that in lupus patients, overly aggressive T cells would also have an overly active metabolism.

To test the idea, the researchers looked at two pathways involved in glucose metabolism: glycolysis and oxidation that occurs in a cell’s energy-generating mitochondria. Compared with T cells from healthy mice, lupus cells had lower pH levels and consumed more oxygen, signs of high rates of glycolysis and mitochondrial oxidation, respectively.

Morel and her team then tested two metabolic inhibitors on lupus mice: 2-deoxyglucose, which inhibits glucose metabolism, and metformin, which slows electron transport in the oxidation pathway in mitochondria. Lupus mice that received the two compounds in their drinking water showed a reversal of symptoms over three months. Levels of autoantibodies dropped, kidney health improved, and T-cell activation returned to normal.

Metformin is already approved by the Food & Drug Administration for treating type 2 diabetes, but Morel says she needs to collect more data on the inhibitors and their effects on the immune system before starting a clinical trial in lupus patients.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society
Comments
Ramesh Pappu, M.D (Fri Feb 20 09:23:23 EST 2015)
Have you considered looking at large prospective cohorts of diabetic patients on oral agents such as metformin and investigate the incidence of systemic lupus. That will be another way at looking at this interesting concept.
Torrie kolbeck (Tue May 09 15:22:43 EDT 2017)
I think that is a great place to start. I am a type 1 diabetic who also has lupus. I have brittle diabetes and so I suggested trying metformin in order to help with my Blood Glucose numbers. Then I read about using metformin to treat lupus. I am always open to being in a trial. Please consider this and feel free to contact me. Thank you
Norma Patricia Gallegos Ríos (Thu Sep 03 11:42:19 EDT 2015)
hola
tengo 46 años de los cuales 8 padeciendo el lupus que inicio en mis articulaciones impidiéndome trabajar el lupus llego hasta mi cabeza provocando convulciones tuve derrame de pleura por lo cual me tuvieron que someter a quimioterapias que me estabilizaron aproximadamente dos años y ahorita regresaron los problemas con las convulsiones con las articulaciones y mi ojo izquierdo no deja brincar me gustaria que pudiera ser yo una de las personas en las que experimentarán o probaran la cura del lupus por que se que será un éxito para poder disfrutar a mis hijas y poder tener un mejor futuro
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