Angiogenesis is a fundamental physiological process of formation of new blood vessels. In adults it is involved in the growth of solid cancers (such as cancer of the breast, colon and prostate) as well as inflammatory disorders such as rheumatoid arthritis and complications of diabetes. Recent clinical successes in cancer with drugs which inhibit angiogenesis, have intensified the interest in this area.
Associate Professor Jennifer Gamble, the leader of the team at the IMVS, said, "Our results suggest that inhibitors of BNO69 alone or in combination with other anti-cancer drugs may be potent inhibitors of the tumourigenesis, targeting not only the tumour cells themselves but also the angiogenic process."
"The publication of BNO69 in a highly regarded scientific journal such as PNAS represents an important step forward for Bionomics. It supports the scientific value of the research and of our proprietary angiogenesis genes as targets for the next generation of anti-angiogenesis therapeutics, which represent a fast-growing and lucrative market," said Dr Deborah Rathjen, CEO and Managing Director of Bionomics.
Bionomics is progressing the development of BNO69 gene silencing molecules as therapeutic candidates in collaboration with the Louisiana Gene Therapy Consortium.
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"The monkeys became extreme workaholics, as evidenced by a sustained low rate of errors in performing the experimental task, irrespective of how distant the reward might be," said Richmond. "This was conspicuously out-of-character for these animals. Like people, they tend to procrastinate when they know they will have to do more work before getting a reward."
To make sure that it was, indeed, the lack of D2 receptors that was causing the observed effect, the researchers played a similar recombinant decoy trick targeted at the gene that codes for receptors for another neurotransmitter abundant in the rhinal cortex: NMDA (N-methlD-aspartate). Three monkeys lacking the NMDA receptor in the rhinal cortex showed no impairment in reward learning, confirming that the D2 receptor is critical for learning that cues are related to reward prediction. The researchers also confirmed that the DNA treatments actually affected the targeted receptors by measuring receptor binding following the intervention in two other monkeys' brains.
"This new technique permits researchers to, in effect, measure the effects of a long-term, yet reversible, lesion of a single molecular mechanism," said Richmond. "This could lead to important discoveries that impact public health. In this case, it's worth noting that the ability to associate work with reward is disturbed in mental disorders, including schizophrenia, mood disorders and obsessive-compulsive disorder, so our finding of the pivotal role played by this gene and circuit may be of clinical interest," suggested Richmond.
"For example, people who are depressed often feel nothing is worth the work. People with OCD work incessantly; even when they get rewarded they feel they must repeat the task. In mania, people will work feverishly for rewards that aren't worth the trouble to most of us."
nimh.nih