Prof. Jeanne Loring is a stem cell biologist, developmental neurobiologist, and geneticist. She is the director of the Center for Regenerative Medicine and professor in the Department of Chemical Physiology at the Scripps Research Institute in La Jolla, California. Her research is currently focused on human pluripotent stem cells, a cell type made by reprogramming adult cells back to an embryonic state, making them capable of developing into all of the cell types in the body.
Prof. Loring is also head of the research team at Summit For Stem Cells, an innovative, patient-lead initiative working to increase awareness and raise funds in support of research working toward a patient-specific neuron replacement therapy for Parkinson’s disease.
The following has been paraphrased from an interview with Prof. Jeanne Loring on November 15th, 2017 discussing her work with iPSCs (induced pluripotent stem cells) and the future of stem cell therapies.
(Full audio version)
When did you start to believe in the promise of iPS cell therapy for Parkinson’s disease and why did you and the team at Scripps decide to pursue iPSCs for transplantation rather than embryonic stem cells?
I had worked on the first fetal cell transplants in the 1980’s and from that believed that a cell transplantation strategy for Parkinson’s disease made sense. So when I was approached with this idea by doctors here in 2011 I said all I needed was the funding and we could begin.
I’d been working with embryonic stem cells for a really long time, I had cell lines on George Bush’s list back in 2001. But in 2007 when Shinya Yamanaka published a method for making pluripotent stem cells from individuals it just made sense to me. I saw no reason why we should continue to immuno-suppress patients after we transplant their cells. I still work with embryonic stem cells, but iPS cells are just better.
What do you say to those who believe iPS cell therapy is too expensive and too technically difficult to be practical for a wider population?
It’s not technically difficult. It was when we started but now iPS cells are no more difficult than ES cells. The challenge was to develop methods to make the same dopamine neurons from every patient, but we solved that problem.
As for cost, it’s a matter of whether you want to invest upfront or downstream. We decided to invest upfront to generate multiple cell lines from our patients. We are meeting some of the same challenges that CAR-T therapies meet for autologous therapies(using patients own cells), that is that we need to come up with really stringent standards to show that each cell line we are using passes those standards. In the end it will not be more expensive than ES cell therapy. It will cost more to generate the cells and develop the assays to show that all the cells are the same but we don’t need to worry about immuno-suppressors or rejection which can be problematic and expensive.
What kind of patients are best suited for iPS cell therapy?
Patient’s that are responsive to L-dopa and don’t have dyskinesia. The FDA will likely make us select patients that are relatively young and responsive to L-dopa. But down the road I want to be able to treat everybody. For now it will depend on how long you have had the disease and the rate of progress of the disease.
When are you hoping to start clinical trials and how will they be structured?
Our timeline is to start in 2019. The first trial will be with local patients so we can monitor them. We have a DBS surgeon as the surgery itself will be similar to DBS. We plan on following these patients forever, the very earliest we might see effects is 6 months, but it will likely take a year before we know. Essentially our criteria are the same as those outlined by the GForce-PD group.
What do you make of the recent positive preliminary results from the stem cell trials in Australia?
Their early success is likely due to a placebo effect, which wears off with time. That’s what we saw in the previous trials. If they are reporting any positive results at this stage it is probably just optimism.
Summit For Stem Cells is unique in its engagement with the patient community, how do you think research benefits from such patient involvement?
Some of my colleagues are frightened of patients and don’t want anything to do with them, others see it as a great idea. I didn’t start this, it was started by and driven by the patients who we educated through lab tours. It does add some challenges in keeping them up to date with everything going on, also seeing them so often we do see some of them getting worse which makes us feel bad that this is taking so much time. But for me the benefits have outweighed the negatives.
Besides transplantation, how are iPS cells helping us better understand Parkinson’s disease and the development of new therapies?
We can use the cells to directly study the cause of the disease. But it is a challenge to model accurately because of how long it takes to develop Parkinson’s disease. For other diseases we are using iPS cells to make progress, for example what happens in the brains of people with autism. We are able to look at genetic forms of autism and identify consistent differences that might be responsible for the disease. We could also use them to better test drugs, so far almost all drugs have failed to go from mice to humans, iPS cells are being used to help make better models to test drugs on.
We can learn a lot from the development of CAR-T therapy in cancer. The first successes were done by taking a person’s own immune cells and modifying them to attack cancer cells then putting them back in. This kind of autologous therapy has a lot of benefits, for one it also eliminates the problems of hosts attacking the graph tissue.
Your lab is also working with the San Diego Zoo to try and save the endangered Northern White Rhino, can you explain the role of iPSCs in this type of work?
The San Diego has what they call a frozen zoo where they have skin cells from 12 different Northern White Rhinos. There are now only 3 left alive and they can’t reproduce. Our idea was to use iPS cells to grow sperm and egg cells and then use in-vitro fertilization to regrow them. But there are limits to what we will be able to do, we cannot regenerate anything that isn’t alive or in a freezer so people’s fears of us creating Jurassic Park are absurd. However some endangered or extinct species for which we do have cells could be brought back.
We’ve actually taken some of the Northern White Rhino cells we do have and reprogrammed them into heart cells, so we have cells from an animal that died 10 years ago beating in a dish here.
What has the approval process with the FDA been like and what if anything could be done to speed up the development of new therapies?
Their main mission is make sure things are safe. Which is relatively easy, it just takes time. We are actually going beyond what they ask by doing whole genome sequencing on our cell lines to make sure they don’t have any cancer causing mutations to set the bar as high as possible.
The FDA does not have rules about these things, they ask us what we plan to do and then advice us on whether that is a good idea. It is very time consuming because of all the back and forth with committees and I’m sure that could be done better. But I don’t want them to just let people do whatever they feel like, there has to be oversight and regulation. I’d like to have more contact with them, I want them to come visit more often to ask tough questions and tell me their concerns, but the system doesn’t work that way which makes it very slow.
What do you believe are the far future applications of the work you are doing? What will we be capable of with stem cells down the road?
There will be a change in the way medicine is done. For certain diseases in which a particular cell type dies cell replacement makes more sense than the alternatives. Again, CAR-T therapies are now bursting onto the scene but they were in development for 20 years. I think stem cell therapy will be similar and one day this will be routine.
Asides from stem cell therapy, what other branches of PD research do you think are the most promising?
The best idea is to try and come up with ways of diagnosing the disease earlier. If we had early diagnosis and drugs that can protect neurons then we give people a lot more time and wouldn’t need a huge intervention.
If I had any spare time I would work on cells that have associated mutations to study how they are different.
For more information visit summitforstemcell.org