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 Company scientists said on Wednesday the protein Activin-A, which
normally blocks bone growth, triggers hyperactive bone growth in
patients with a genetic mutation that causes the disease. The
disease is known as Fibrodysplasia Ossificans Progressiva, or FOP.
The researchers showed that an antibody that blocks Activin-A helped
shut down the growth signal in genetically modified mice. The effect
lasted as long as six weeks, according to the study, published in
the journal Science Translational Medicine.
Aris Economides, executive director of skeletal diseases and
co-founder of the Regeneron Genetics Center, said the findings could
eventually lead to a treatment for the disease. FOP is a lethal
genetic disorder in which muscle and soft tissue gradually are
replaced by bone, forming an extra skeleton that immobilizes and
eventually suffocates patients.
The condition currently affects 800 people globally, including 200
in the United States.
FOP is caused by mutations in the gene ACVR1 which makes a receptor
that controls bone growth in cells. Regeneron discovered that this
mutated receptor has an abnormal response in the presence of Activin-A,
a growth factor often secreted by the immune system in response to
injury and inflammation.
Normally, Activin-A blocks the receptor, putting the brakes on bone
growth. In individuals with the FOP mutation, Activin-A has the
opposite effect. "It's as if the brakes are hot-wired to the gas
pedal," Economides told Reuters.
The finding explains how abnormal bone forms in FOP patients, often
in response to injuries or illness that cause tissue swelling or
inflammation, he said.
To test their finding, researchers developed a therapeutic antibody
designed to block Activin-A. When injected in mice that developed a
form of the disease, the drug blocked the formation of excess bone.
Economides said the antibody works in a similar way to Regeneron and
Sanofi's newly approved antibody drug Praluent, a
cholesterol-lowering drug which blocks a receptor called PSCK9 on
liver cells that controls the removal of "bad" LDL cholesterol.
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Betsy Bogard, director of global research development for the
International FOP Association and the sister of an FOP patient,
called Regeneron's findings "incredibly exciting," as they help
explain some of science behind FOP and also raise hope for a new
treatment approach.
But Bogard, who is a former executive of the drug company Genzyme, a
unit of Sanofi, remained cautious.
"The road of developing drugs is long and difficult. There is still
much to learn," she said.
Although the company would not disclose details or timing of its
development approach, Regeneron spokeswoman Alexandra Bowie said
preclinical testing is ongoing, and the company hopes to move the
treatment into human trials.
Clementia Pharmaceuticals Inc, a private Montreal-based company, is
also studying FOP and is testing a compound called palovarotene. The
drug is a repurposed compound acquired from Roche that aims to
interrupt the process of bone formation during disease flare-ups. It
is now being tested in a phase 2 trial in FOP patients.
Last month, Clementia expanded the trial to include children as
young as 6, and said it expects to start phase 3 testing in the
second half of next year.
(Reporting by Julie Steenhuysen; Editing by Frances Kerry)
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