Researchers from Massachusetts General Hospital, part of Mass General Brigham healthcare system, utilized a recently approved recombinant form of human ADAMTS13 to rescue a young mother suffering from immune thrombotic thrombocytopenic purpura (iTTP), an uncommon condition causing excessive blood clotting in small blood vessels. This groundbreaking use of the drug for iTTP is detailed in the New England Journal of Medicine.
id=”text”>
The medication is a modified version of the enzyme that is missing in iTTP. The lead author, Pavan K. Bendapudi, MD, who works in the Division of Hematology and Blood Transfusion Service at Massachusetts General Hospital and also teaches at Harvard Medical School, stated that the drug successfully reversed the disease process in a patient with a severe form of iTTP.
iTTP occurs when the body’s immune system attacks an enzyme called ADAMTS13, which is responsible for breaking down a protein involved in blood clotting. The current main form of treatment for this life-threatening condition is One treatment for blood disorder is plasma exchange, which eliminates harmful autoantibodies and provides extra ADAMTS13. Although plasma exchange can induce a positive clinical response in most patients, it can only restore about half of normal ADAMTS13 activity at best. On the other hand, a synthetic form of human ADAMTS13 (rADAMTS13) has the potential to greatly increase ADAMTS13 delivery.
rADAMTS13 was recently approved for patients with congenital thrombotic thrombocytopenic purpura, a condition that occurs in patients born with a complete loss of the ADAMTS13 gene. It is uncertain whether rADAMTS13 could be effective in treating iTTP due to the presence of inhibitory anti-ADAMT.S13 autoantibodies, but Bendapudi and his colleagues received permission from the US Food and Drug Administration to utilize rADAMTS13 donated from the manufacturer under a compassionate use protocol in a dying patient with treatment-resistant iTTP.
“We discovered that rADAMTS13 quickly reversed this patient’s disease process despite the current belief that inhibitory autoantibodies against ADAMTS13 would make the drug ineffective in this condition,” said Bendapudi. “We were the first doctors to use rADAMTS13 to treat iTTP in the United States, and in this case it helped to save the life of a young mother.”
Bendapudi noted that the iThe patient’s inhibitory autoantibodies were overcome by rADAMTS13, which reversed the thrombotic effects of iTTP. This effect was observed almost immediately after the failure of daily plasma exchange to induce remission.
“I believe rADAMTS13 has the potential to become the new standard of care in acute iTTP. We will need larger, well-designed trials to assess this possibility,” said Bendapudi.
A phase 2b randomized clinical trial of rADAMTS13 in iTTP was recently started.
