Clinical depression and other neurological disorders have become a pandemic almost as widespread as the coronavirus, with one in six of the world’s population suffering from neurological disorders. And hundreds if not thousands of technology and drug companies are vying for a cure for these diseases.
One Israeli company, Nextage Therapeutics, has developed a technology that it believes could refine the use of psychedelic molecules – also known as hallucinogens – to better treat these people.
In the 1950s, ‘60s and ‘70s, thousands of research studies were carried out to demonstrate the benefits of psychedelics – psilocybin, mescaline, LSD and DMT, for example – as a tool for treating post-traumatic stress disorder (PTSD), depression and other psychiatric disorders. But in 1970, when then-president Richard Nixon introduced his Controlled Substances Act, all of these drugs became illegal.
For three decades, the research stopped.
However, according to Nextage Founder and CEO Abraham Dreazen, there has been a shift in the last decade. The US Food and Drug Administration, for example, is starting to see quality of life as a factor in evaluating medicine, opening the door to these drugs.
The FDA named psilocybin therapy – currently being tested in clinical trials – as “breakthrough therapy,” which should speed up the process of drug development and review.
Psilocybin is made of chemical compounds obtained from hallucinogenic mushrooms.
It also gave the breakthrough therapy designation to MDMA for the treatment of post-traumatic stress disorder. MDMA is the chemical name for the drug commonly known as “ecstasy.”
Israel is just now joining these kinds of efforts.
Earlier this year, Nextage signed an agreement with MindMend, one of the pioneers in this new wave of psychedelic pharmaceutical development, to use its proprietary “Brain Targeting Liposome System” (BTLS) delivery technology to optimize the delivery of drug products based on noribogaine, and ultimately other ibogaine derivatives.
Ibogaine is a drug harvested from the roots of a plant found in the coastal Central African country of Gabon. Researchers are studying it for use in the treatment of opioid addiction. But the drug is not without side effects. A release by MindMed explained that today, “orally administered ibogaine and noribogaine present unacceptable safety risks due to their torsadogenic effects at high systemic concentrations.”
In layman’s terms, Dreazen explained, the drug can cause heart attacks. But his company believes that if it is able to reduce the administered dose while maintaining the same amount of the drug that makes it into the brain as opposed to the rest of the body, including the heart, “that is the [winning] lottery ticket.”
The challenge for any drug being used to treat a neurological disorder or even brain cancer is that the blood-brain barrier, in its effort to protect the brain, prevents around 95% of foreign molecules from getting through. To work around that, most current drug therapies targeting the brain and the central nervous system are given at extremely high doses so that enough will get where it needs to go. The downside is that whatever does not make it through the barrier gets systemically dispersed throughout the body, often causing severe side effects.
The BTLS platform, licensed from the Technion-Israel Institute of Technology four years ago and further developed internally since then, uses a liposomal vehicle with a unique targeting complex that allows blood-brain barrier permeation and brain-specific delivery of all kinds of agents.
Using liposomes in drug delivery is nothing novel, Dreazen admitted. The concept is well-known in pharmacology. In fact, both the Pfizer and Moderna COVID-19 vaccines are delivered into our body using these fatty acid capsules.
But Nextage has attached a “small arrow” of seven amino acid peptides – essentially a very small protein – which is part of a much larger protein that is native to the brain and has a way of actively transporting the liposomal capsule through the blood-brain barrier. Once the capsule is drawn into the brain with the arrow, it gets lodged there and starts dissolving, facilitating release of the active material – the drug.
This allows pharmaceutical companies to substantially reduce the necessary dosage and hence the side effects.
“It is really a glimpse at hope in the pharma world,” Dreazen said.
THE COMPANY has already completed a lot of preclinical work showing the efficacy and universality of its technology. About a month ago, it finished a first safety-toxicity study with cannabidiol and is now in the planning process of a Phase I/II clinical trial for the delivery and use of CBD for certain conditions.
Nextage, based in Ness Ziona, is part of a group that has been in the drug delivery business for 14 years. Its daughter company, IMIO, is focused on psychedelics. The company completed a $2 million funding round a couple of months ago.
Another compound the company hopes to look at is lysergic acid diethylamide, otherwise known as LSD. Dreazen said LSD “is a really promising drug.” Its challenge is that when taken, people can “trip” for 15 to 17 hours, making it very unfeasible as a chronic treatment. But just like with ibogaine, he believes that if the dose can be reduced and the least amount possible gets into the body as opposed to the brain, “you could potentially get the same therapeutic effect without the longevity of the trip.”
“In the US, the psychedelic movement has exploded in the last 12 months,” Dreazen said. “I think psychedelics in Israel are just emerging, and we are the first public company to really put our teeth into it. Israel has always been in the forefront of research and development and we are committed to spearheading this industry.”