Novel therapy to reduce bone loss in certain patient populations

Description:

Market Need

Osteoporosis is a prevalent but grossly undertreated condition, with only 10% of individuals with osteoporosis in Australia being treated. In women, osteoporosis is a serious consequence of menopausal bone loss. Destructive bone erosion is also a serious complication of several primary and metastatic musculoskeletal cancers, and chronic inflammatory diseases, such as rheumatoid arthritis. Altered bone remodelling also contributes to osteoarthritis; another highly prevalent and debilitating disease.

 

By 2025, the US osteoporosis drug market is estimated to reach $16.3bn, primarily due to an increasingly unhealthy lifestyle, aggravating the prevalence of osteoporosis. Patent expiries have also allowed more competitors to emerge in the osteoporosis market.

 

Existing medications are based on orally administered anti-resorptives, such as Bisphosphonates, which slow the rate of bone breakdown. Denosumab is another anti-resorptive treatment, administered via a 6 monthly injection.

 

Most marketed treatments for osteoporosis target bone loss via the osteoclast.  There are significant side effects and drawbacks to many of the existing treatments for osteoporosis via this mechanism, such as their long-acting nature, perceived risk of osteonecrosis of the jaw and atypical femoral fracture, which influences their uptake by physicians and prospective patients. Cessation of Denosumab treatment is associated with a bone loss ‘rebound’ effect. Some of the available antibody-based treatments for osteoporosis (e.g. Denosumab, Teriparatide) are also expensive. Furthermore, most treatments are only used when bone has  already been lost.

 

The Technology

Through clinical, medicinal chemistry and biology collaborations, researchers at the University of Adelaide have identified both a novel target, and a novel mechanism of action, to treat and prevent bone loss.  Working with a research compound to inhibit a specific Carbonic Anhydrase (CA), our team is targeting the Osteocyte, rather than the Osteoclast, hypothesising that this mechanism of action should result in lower side effects, and reduced risk of rebound post treatment. 

 

The research team has knocked out the identified CA in a mouse model, which validated the role of the specific CA in maintaining bone mass.  Mouse studies have also been conducted to show that the research compound can effectively inhibit the CA identified.

 

IP Position

A provisional patent has been filed by the University of Adelaide, with a priority date of February 2018.  The patent covers the modulation of the identified CA, and its effect on bone loss in a number of indications.

 

Our collaborator has filed a PCT on the composition of matter over the research compound being used in our studies to inhibit the CA.  We envisage additional research and development will be required to optimise the compound for commercialisation.  Additional test compounds are being considered for use.

 

Next Steps

Over 2018, the research team is focussed on looking at the impact of transient inhibition of the CA on bone loss in a perimenopausal mouse model, as women lose almost half their total bone density in their first 10 years post-menopause, significantly increasing their risk of osteoporosis.

 

The team is also looking at the role of the CA in Giant Cell Tumour of Bone (GCTB) formation and the associated bone loss, using ex vivo human cell models. GCTBs may be designated orphan status, for the purpose of regulatory approval.

 

For Information, Contact:

Kirsten Bernhardt: +61 407 163 717

Email:Kirsten.Bernhardt@adelaide.edu.au

 

 

Patent Information:
Category(s):
Medical
For Information, Contact:
Michael Muthig
Commercial Manager
The University of Adelaide
michael.muthig@adelaide.edu.au
Inventors:
Gerald Atkins
Keywords: