Credit: NHLBI
The apoptosis inhibitor aurin tricarboxylic acid (ATA) is active against paroxysmal nocturnal hemoglobinemia (PNH), according to research published in PLOS ONE.
PNH is a rare condition in which red blood cells (RBCs) become vulnerable to attacks by the complement immune system and subsequently rupture.
This can lead to complications such as anemia, kidney disease, and fatal thromboses.
PNH results from a lack of 2 proteins that protect RBCs from destruction: decay-accelerating factor (CD55), an inhibitor of alternative pathway C3 convertase, and protectin (CD59), an inhibitor of membrane attack complex (MAC) formation.
Because previous studies suggested that ATA selectively blocks complement activation at the C3 convertase stage and MAC formation at the C9 insertion stage, researchers thought ATA might prove effective against PNH.
First, they compared RBCs from 5 patients with PNH (who were on long-term treatment with eculizumab) to RBCs from healthy individuals.
Despite the eculizumab, the PNH patients’ RBCs were twice as vulnerable to complement-induced lysis as the healthy subjects’ RBCs. And western blot revealed both C3 and C5 convertases on the membranes of patients’ RBCs.
However, when the researchers added ATA to patients’ blood samples, the RBCs were protected from complement attack. In fact, the drug restored the RBCs’ resistance to the same level as normal RBCs.
“Our study suggests that ATA could offer more complete protection as an oral treatment for PNH, while eliminating the need for infusions,” said study author Patrick McGeer, MD, PhD, of the University of British Columbia in Vancouver, Canada.
“PNH is a disease that may happen to anyone through a chance mutation, and, if nature were to design a perfect fix for this mutation, it would be ATA.”
Dr McGeer added that many diseases are caused or worsened by an overactive complement immune system. So his group’s findings could have implications for conditions such as Alzheimer’s disease, Parkinson’s disease, macular degeneration, amyotrophic lateral sclerosis, multiple sclerosis, and rheumatoid arthritis.
He and his colleagues are now proceeding with further testing, and Dr McGeer expects ATA could be available in clinics within a year.
