hereditary exostoses (MHE) is a rare genetic disease which results in
development of multiple bone tumors.
- The only
treatment available today is surgical removal of the tumors.
- A new study
identifies the mechanism of osteochondromagenesis and a potential therapy
for MHE using BMP inhibitors.
every 50,000 people is affected with multiple hereditary exostoses (MHE). MHE
is a rare genetic disease characterized by multiple bone tumors, affecting
children during their growing years. Very limited treatment options and the age
group that is affected emphasize the need to develop effective therapeutic
strategies in treating the disease. A study conducted at the Sanford Burnham
Prebys Medical Discovery Institute, USA, was successful in discovering the
underlying mechanism of disease manifestation and also provide a potential
therapy to treat MHE. The study was published in The Journal of Clinical
MHE is a
genetic condition where people develop multiple benign (noncancerous) bone
tumors called osteochondromas
. MHE is also called Bessel-Hagan
Disease, Multiple Osteochondroma, Familial exostoses, among others. The number
and location of the tumors vary greatly from person to person. They generally
form around areas of active bone growth like the knee, shoulder blades, hips
and elbows, thereby restricting growth and movement. Osteochondromas are
generally benign, although they may become cancerous and spread to other parts
of the body. Estimates suggest that MHE has a 1 in 20 to 1 in 200 lifetime risk
of becoming cancerous osteochondromas called sarcomas, which are deadly.
‘BMP inhibitor called LDN-193189 was successful in suppressing bone tumors in MHE mouse models.’
is a genetic condition, the disease may be passed on to children from affected
parents. MHE is caused due to mutations (changes in DNA) in either EXT1 or EXT2
genes. The symptom severity is higher when the mutation is in the EXT1 gene.
MHE is inherited in an autosomal dominant manner, which means that if any one
parent is affected, the child has a 50% risk of inheriting the condition. The
condition affects both males and females equally.
affected children are born with the mutation, osteochondromas are not present
at birth, however 96% of affected children develop tumors by the age of 12.
Genetic testing and prenatal testing is extremely important in pregnancies with
a family history of MHE.
there is a genetic basis for the disease, 15% of people affected with
osteochondromas, do not have mutations in EXT1 or EXT2 genes. The reason for
this is still unknown. This may indicate that other genetic alterations or
epigenetic (genetic and environmental) factors may lead to the disease
through a study on MHE mouse models have provided new insight into the
mechanism of the disease and also proposed a therapeutic strategy to suppress
the bony tumors. The discovery could led to the first ever drug for patients
affected with the disease.
study, it was unclear how normal bone growth becomes abnormal in MHE patients.
Professor Yu Yamaguchi at SBP said that this was essential to devise strategies
to prevent, stop and maybe even reverse tumor growth.
- Stem cells of
developing bone called the mesenchymal stem cell-like progenitor cells residing in the
perichondrium is the cell type that
gives rise to tumors in MHE.
- Enhanced or overactive Bone Morphogenic Protein (BMP) signaling in
these cells is the primary cause for osteochondromagenesis (formation of
- A BMP inhibitor
called LDN-193189 was used to treat the MHE mouse models and it was
successful in suppressing the formation of bone tumors.
"Our goal is to look for suitable drugs --
small molecule BMP inhibitors -- that we can refine for efficacy and
selectivity for use in humans. We want to develop the first effective therapy
to improve the lives of MHE patients," adds Dr. Yamaguchi.
- Hereditary Multiple Osteochondromas - (https:ghr.nlm.nih.gov/condition/hereditary-multiple-osteochondromas#synonyms)
- Inubushi, T., Nozawa, S., Matsumoto, K., Irie, F., & Yamaguchi, Y. (2017). Aberrant perichondrial BMP signaling mediates multiple osteochondromagenesis in mice. JCI Insight, 2(15). doi:10.1172/jci.insight.90049