Dr. Schubert, could you please tell us what motivated you to take on this extremely challenging disease?
There was an enormous unmet need, and we had some unique methods in our laboratory to initiate a new and different approach to Alzheimer’s disease ( AD) drug discovery. Several of my neighbors were dying of AD, and this was the only way I knew how to help.
You and your team have been working on naturally grown products and identifying compounds to prevent nerve cell death. Could you please explain in lay person’s terms how this is different from what the pharma majors have been trying to do, and which are the naturally grown products you’re working on?
The pharmacuetical companies insist upon developing drugs based upon a preselected molecular target and making drugs to inhibit that target. The problem is that for many conditions in the brain the companies do not know what is the proper target to inhibit. In sharp contrast, we make drugs based upon their ability to inhibit toxic conditions that occur in the old brain, such as low energy metabolism, the accumulation of damaged proteins, and inflammation. We use nerve cells in our assays because these are what die in people with AD, and we do not know the molecular target of the drug candidate, only that it protects the nerve cells from toxic events. We then figure out the target. This method is called phenotypic screening, because we are assaying the condition of the cell (phenotype, for example, dead or alive), not a specific target. We started with plant natural products because most of the drugs in the clinic today started with plant chemicals and were discovered by assays like ours, not the current pharma approach, which they use because it is much easier and faster than phenotypic screening. We started by screening thousands of plant products, but are currently focused on those related to curcumin and a chemical in strawberries. We first identify the natural chemical, and then improve it by medicinal chemistry to make it more drug-like.
Your efforts have also been focused on preventing Alzheimer’s disease and strokes. Could you tell us more about this?
Our drug candidates were designed to help in conditions where nerve cells in the brain die. AD and stroke are two of the major old age associated conditions where this happens, and therefore we focused the animal testing of our compounds on them.
Curcumin, the curry spice, has since ancient times been known for its medicinal properties. Please tell us about your work and progress based on the compounds found in this spice.
A friend of mine, Greg Cole at UCLA, found that the major chemical in curry spices, curcumin, was effective in some mouse models of AD, and at the same time we identified it through our assays. However, curcumin has very poor properties as a drug – it does not easily get into the brain and is broken down in the gut and blood very rapidly. We decided to use chemistry to modify it to make it more drug-like. This worked very well, and we hope to start clinical trials soon with the new AD drug candidate called J147. However, we have not yet been able to obtain the necessary funding, but we are still trying.
Is it correct that those living in India, Sri Lanka, Pakistan, and other Asian countries who consume Curcumin in their daily diet do not suffer from Alzheimer’s and other neuro degenerative disorders in the same percentage terms as those living in the Western world?
This is correct.
Please tell us about your work with Marijuana.
There have been claims that MJ may have clinical efficacy in various neurological conditions. Since working with MJ is illegal in most places, there have been no good clinical trials for any condition with MJ. And since we knew that some of the molecular pathways were shared between the active ingredients in MJ and our drug candidates, we decided to have a look using our assays. We were able to show that using a simple assay with human neurons it is possible to remove the toxic proteins associated with AD from cells. This does NOT show that MJ has clinical efficacy in any disease, but it does demonstrate that there is a great potential that should not be discarded because of antiquated laws. Much more work at the clinical level needs to be done.
Please tell us about your growing up years and those who inspired you the most.
My father was a policeman, and my mother was a secretary. They were not ‚intellectuals‘ but made my brother and me work very hard in school to get good grades. In high school I wanted to be an engineer (my brother became one), but I had a great high school science teacher who got me interested in chemistry and biology. I got a partial scholarship to a very modest university, but was able to work in the labs to pay for the remaining costs and have not stopped working in the lab to this day. The single most important thing is that I was very lucky to have great teachers and be able to figure out what I really liked doing as a profession at an early age (high school). For most people it takes longer to figure this out!
What do you do when you are not working?
Reading, gardening, and sports.
Our readers consist mainly of young adults in different parts of the world who look up to high achievers such as yourself for inspiration. A word of advice for them?
Get exposed to many things in life and different subjects in school in order to find something that really turns you on – something you want to do the rest of your life. Sometimes this takes quite a while, but in any case work hard at school and try to get the best grades in all subjects that you can. Once you find this favorite subject, set some goals (getting a specific kind of job, getting an advanced degree) and work as hard as possible to atain them. The most important thing is that you are happy and do the best you can to help those around you who may not be as fortunate.
Photo: From Archive of Dr. David Schubert