Disc Medicine planning trial of iron overload treatment for sickle cell
Problem is common one in SCD due to frequent blood transfusions
Disc Medicine says it’s planning to launch a clinical trial before the end of the year that will test DISC-3405, its treatment candidate for reducing high iron levels and easing iron overload, in people with sickle cell disease (SCD).
“We’re … excited about the progress across our iron homeostasis [balance] portfolio, DISC-0974 and DISC-3405, as these programs will be important drivers of Disc’s future growth,” John Quisel, PhD, Disc’s CEO and president, said in a company press release outlining its “anticipated milestones.”
“We … plan to initiate … a Phase 1b trial of DISC-3405 in sickle cell disease by year end,” Quisel said.
The company did not provide further details about the trial’s design or timeline, but noted its launch among its “key near-term business objectives.”
A genetic disorder, SCD is caused by mutations in a gene that encodes a subunit of hemoglobin, the protein that red blood cells use to carry oxygen through the bloodstream.
This results in the production of an abnormal version of hemoglobin that is prone to clumping in red blood cells, and which deforms cells into the sickle shape that gives the disease its name. These deformed cells are more likely to get stuck in blood vessels and block blood flow, and they also are vulnerable to being destroyed, which can lead to anemia.
Without treatment, iron overload can damage liver, heart
To treat anemia, people with SCD and other blood disorders are commonly given blood transfusions. This can provide a fresh supply of healthy blood cells, thereby improving blood flow and oxygen delivery.
But because blood is very rich in iron, getting frequent transfusions can also lead to dangerously high iron levels — know as iron overload — which can damage organs such as the liver and heart.
Formerly known as MWTX-003, DISC-3405 is an antibody-based therapy designed to reduce iron levels by targeting transmembrane serine protease 6 (TMPRSS6), a protein involved in iron metabolism.
The TMPRSS6 protein suppresses the production of a hormone called hepcidin that helps to control how the body absorbs and stores iron. By blocking TMPRSS6, DISC-3405 is expected to increase hepcidin levels, which will ultimately reduce iron levels.
This mechanism of action mimics what happens naturally in people carrying mutations in the gene that encodes TMPRSS6, which makes them less likely to experience problematically high iron levels, Disc states on its website.
The company is hoping to develop DISC-3405 to treat a variety of conditions marked by iron overload. One such condition is polycythemia vera, a rare blood cancer, and the therapy is already being tested in this patient population in a Phase 2 trial.
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