July 2021
Quarterly Research Update
So on the 6th of July I was very privileged to have an online chat with Susan Hedstrom and Theresa Strong from FPWR in the USA. We chatted for over an hour about the latest news in research. It was a very useful and productive chat which we will continue on a quarterly basis to keep everyone informed of the latest news in one succinct summary. So here is the latest………….
There are two main areas to report on; clinical trials for therapeutics and genetic research.
1) Clinical trials for therapeutics
DCCR
DCCR works by decreasing the activity of hunger neurons in the hypothalamus.
Hopefully by now you have heard the good news that the FDA has indicated that it is willing to review data from Soleno to determine whether or not an additional clinical trial is needed, or if Soleno can go ahead and submit a new drug application. Soleno expects to submit data from the “DESTINY PWS” clinical trial and the “C602” extension study to the FDA in the 3rd quarter of the year. Obviously the FDA is different to the EMA (European Medicines Agency) but this is a step in the right direction. If the drug gets approved with one licensing organisation it is far easier to get approval from others.
Obviously the FDA is different to the EMA (European Medicines Agency) but this is good news for all as once a drug gets approved with one licensing organisation it is far easier to get approval from others.
Carbetocin
Carbetocin works as an oxytocin receptor agonist (i.e can trigger the same response as oxytocin in the body – reducing anxiety & hunger and improving bonding etc) but may not have some of the potential side effects, such as increased anxiety, that can come from giving too much oxytocin as a medication. A Phase 3 study of carbetocin in PWS was recently completed by Levo Therapeutics.
Exciting times for this drug as a New Drug Application has already been submitted to the FDA. A decision about approval may come before the end of the year.
Pitolisant
Pitolisant works by activating Histamine H3 receptors in the brain. This increases the activity of certain brain cells called ‘histamine neurons’, which are important for keeping the body awake.
A Phase 2 trial is currently enrolling in the USA with the primary target of reducing daytime sleepiness. Given ongoing challenges with COVID-19, recruitment has been slower than expected, but hopefully will accelerate soon.
Cannabidivarin (CBDV)
A Phase 2 trial is currently enrolling in the USA with the primary target of improving behaviour.
Guanfacine
Guanfacine is thought to respond to parts of the brain that lead to strengthening working memory, reducing distraction, improving attention and impulse control.
A phase 4 trial is currently enrolling in the USA with the primary target of reducing aggression and self-injurious behaviour.
Tesomet
Tesomet works by inhibiting reabsorption of three neuortransmitters serotonin, dopamine and norepinephrine. Serotonin is the key neurotransmitter that stabilizes our mood, feelings of well-being, and happiness. This chemical signal impacts your entire body. It enables brain cells and other nervous system cells to communicate with each other. Dopamine plays a critical role in pleasure, attention, mood, and motivation, while norepinephrine is important in energy expenditure.
Phase 2 trial is complete and Phase 2b is coming in October with the primary target of improving hyperphagia and weight loss. The great news is that one of the trial sites for this therapeutic will be run by Tony Holland in the UK.
2) Genetics research
Genetic research is currently focusing around the following areas
- Activation of maternal chromosome 15
In PWS, it is the absence of the paternal genes on chromosome 15 (either through deletion on the paternal chromosome or absence due to UPD) that cause PWS. Research is ongoing into the effect of switching on the counterpart genes on the maternal chromosome.
- Cellular phenotypes of PWS
This involves looking at stem cells of those with PWS and studying the differences from stem cells from a non PWS individual. Once these differences are clear, these stem cells will be pivotal in drug testing to see how the drugs affect the atypical functioning of PWS cells).
- Organoids
Organoids are tiny, self-organised three-dimensional tissue cultures that are derived from stem cells. Such cultures can be crafted to replicate much of the complexity of an organ. In the case of PWS organoids were developed to form part of a brain. When the PWS organoid was compared to a non PWS organoid some interesting differences were revealed. The PWS organoids were slower to mature and differentiate, less responsive to leptin and promoted higher levels of inflammation. These organoids will be really useful in the future for screening new drugs and the revelation of increased inflammation provides a new target for therapeutics.