Could a combination treatment with an antidepressant be an interesting opportunity for DexTech Medical's candidate OsteoDex?? The company's CEO Anders R Holmberg shares his views on the new American findings here.
A study on mice shows that the body's own MAOA enzyme is an important and contributing factor to prostate cancer cells spreading with metastases and breaking down bone. Now, American researchers have found that an older generation of anti-depressants appears to be able to slow down the effect of the MAOA enzyme and disrupt the signals that lead to bone metastases. The study has been published in the reputable scientific journal Cancer Cell.
In advanced prostate cancer, metastases spread to the bones, a fatal and incurable condition that causes about 90 percent of all deaths from this type of cancer. In the current study on mice with prostate cancer, the researchers lowered the concentration of the MAOA enzyme in the body, whereupon it was seen that bone metastases decreased, and conversely, they increased when the researchers overexpressed the enzyme. From this, the research team was able to conclude that MAOA is important in the process of curbing the risk of prostate cancer metastasizing to bones.
Cancer cells can specifically activate osteoclasts to break down bone
The MAOA enzyme triggers a chain of events that activates three specific types of proteins, which in turn promote the breakdown of bone by bone cells called osteoclasts, which normally absorb bone material during bone formation, but are overactive in mice with bone metastases from prostate cancer. The cancer cells thus specifically activate the osteoclasts to break down bone, while the osteoclasts stimulate tumor growth.
The antidepressant drug clorgyline inhibits the enzyme
Intriguingly, it was an antidepressant called clorgyline, which is no longer in widespread clinical use, that inhibited the MAOA enzyme, thereby preventing the chain of events that leads to bone breakdown. As far as is known, there are no previous studies that suggest that there is a lower risk of developing bone metastases in prostate cancer if antidepressants are taken at the same time, and indeed the researchers also emphasize that the promising results in mice will require further investigation. For example, the formulation, dosage and delivery route of MAOA inhibitors need to be adjusted before they can lead to a final clinical application.
DexTech Medical's drug candidate
DexTech is developing a targeted and dual-acting drug to prolong the life of patients suffering from prostate cancer with bone metastases (OsteoDex). DexTech has developed a patented technology platform and from this has derived four drug candidates with patents/patent applications in several key markets. DexTech's goal is to out-license each drug candidate after the completion of a phase II study at the latest. The interesting thing about the new study for DexTech Medical is whether the new findings form a basis for considering a combination treatment. Below we have asked the company's CEO Anders R Holmberg that very question.
About MAO inhibitors
MAOA inhibitors or monoamine oxidase inhibitors have been used as antidepressants since the 1950s, but have increasingly been replaced by newer types of substances. The drugs in this class work by inhibiting monoamine oxidase (MAO), a type of enzyme in the brain that breaks down certain neurotransmitters (monoamines), especially serotonin and noradrenaline and dopamine. An example of an approved MAO inhibitor drug in Sweden is moclobemide, which is marketed under the brand name Aurorix, among others. Other drugs are selegiline, brofaromine, phenelzine, iproniazid, isocarboxazid, moclobemide, nialamide, toloxatone and tranylcypromine.
Anders R Holmberg, CEO of DexTech Medical, what do you think about the findings that have now been published in Cancer Cell?
– These are interesting findings that provide further knowledge about the complexity of the factors that influence the development of bone metastases.
Is there anything in the study that surprises you?
- It is interesting when old drugs for completely different indications prove relevant in this context. One should feel humble. and respect for the complexity, there is no simple solution but synergy between different drugs is the way forward. Again, the challenge is to break the so-called vicious cycle of bone breakdown and tumor growth that has been noted to be of primary importance in CRPC.
MAOA inhibitors have a broad side effect profile but on the other hand they can potentially enhance the effect of other drugs. How do you view the possibility of testing OsteoDex in a combination study with an MAOA inhibitor?
– Definitely interesting in the future, but there are also other preparations, i.e. those currently used in CRPC, which are probably of more primary interest. Overall, there are likely to be successes to be gained from combination treatments.
Read also: Continued good prospects for DexTech's prostate cancer study
Read more about the study in Cancer Cell
The content of Biostock's news and analysis is independent, but Biostock's operations are to some extent financed by companies in the industry. This post refers to a company from which BioStock has received funding.
Get all the news and analysis directly on your mobile with BioStock's mobile app!
