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Clinicians report first successful drug test for patient with life-threatening blood clotting disorder

Clinicians report first successful drug test for patient with life-threatening blood clotting disorder


A team led by researchers at Massachusetts General Hospital, a founding member of Massachusetts General Hospital, used a new drug to save the lives of patients with immune thrombotic thrombocytopenic purpura (iTTP). iTTP is immune thrombotic thrombocytopenic purpura, a rare disease characterized by uncontrolled clotting throughout its life. small blood vessels. This group describes the first clinical use of the drug for iTTP. New England Medical Journal.

“We have shown that this drug, a genetically engineered version of the missing enzyme in iTTP, can reverse the disease process in very critically ill patients,” said lead author Pavan K. Bendapudi, MD. said the doctor. He is a researcher in the Division of Hematology and Transfusion at Massachusetts General Hospital and an assistant professor at Harvard Medical School.

iTTP is caused by an autoimmune attack on an enzyme called ADAMTS13, which is responsible for cleaving large proteins involved in blood clotting. The current mainstay of treatment for this life-threatening blood disease is plasma exchange, which removes harmful autoantibodies and provides additional ADAMTS13. Although plasmapheresis induces a clinical response in most patients, it can restore, at best, only about half of normal ADAMTS13 activity. In contrast, a recombinant form of human ADAMTS13 (rADAMTS13) offers the potential to significantly increase ADAMTS13 delivery.

rADAMTS13 was recently approved for patients with congenital thrombotic thrombocytopenic purpura. Congenital thrombotic thrombocytopenic purpura occurs in patients with congenital thrombotic thrombocytopenic purpura. ADAMTS 13 gene. Although it is questionable whether rADAMTS13 is effective in iTTP given the presence of inhibitory anti-ADAMTS13 autoantibodies, Bendapudi et al. permission was obtained to use rADAMTS13 in dying patients. His iTTP is treatment-resistant.

“We found that rADAMTS13 rapidly reversed the disease process in this patient, despite the current wisdom that inhibitory autoantibodies to ADAMTS13 render the drug ineffective in this condition,” Bendapudi said. “We were the first doctors in the United States to use her rADAMTS13 to treat her iTTP, and in this case it helped save the young mother's life.”

Bendapudi noted that the injected rADAMTS13 overwhelmed the patients' inhibitory autoantibodies and reversed the thrombotic effects of iTTP. This effect was observed immediately after administration of rADAMTS13 after daily plasma exchange failed to induce remission.

“We believe that rADAMTS13 has the potential to replace the current standard of care in acute iTTP. Larger, well-designed trials are needed to evaluate this potential,” Bendapudi said. .

A phase 2b randomized clinical trial of rADAMTS13 in iTTP was recently initiated.




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