Prof. Lorenz Studer is the founder and director of the Center for Stem Cell Biology at Memorial-Sloan Kettering Cancer Center in New York City. His lab is at the forefront of developing cell replacement therapies for Parkinson’s disease. In 2015, he was named a recipient of the MacArthur Fellowship (also known as the “Genius Grant”) for his innovative work on stem cells and Parkinson’s disease research.
The following questions and answers have been paraphrased from a conversation with Prof. Lorenz Studer on October 11th, 2017 discussing the stem cell trials his lab is set to begin in 2018.
When do you expect phase 1 of your clinical trials to begin?
The earliest start date would be April 2018. However, there are still many steps that need to be taken, making it difficult to accurately predict when we will begin. We have produced all the cells and tested them in 500 rodent models looking for tumor growth. We are also testing them in non-human primates. Additionally, we are also running an observational study to evaluate the methods we will use during the trial to follow each patient. Once we have all the data from those animal models and from our observational study we can proceed. The summer of 2018 may be a more realistic target.
How will the trial be structured?
It will be an open label study, meaning each patient will know what they are getting. Trial participants will also be on immuno-suppressants for 12 months post operation to ensure the bodies immune system does not reject the transplants. We expect the symptomatic benefits will start to be felt 12-18 months afterwards, with the full effect taking roughly 3 years.
We are still discussing the details of how the trial is going to be run with the other members of the GForce-PD.
What kind of patients are you going to be recruiting?
The criteria have not been finalized but, at the moment, we will exclude patients with GBA mutations as they are associated with a faster rate of disease progression. The patients selected will likely be between 40 and 70 years old who have had the disease for at least five years. We are going to recruit 10 patients for the phase 1 study based on those that have a high probability of success and represent a wide a range of PD patients.
How are you going to measure the success of the trial?
The primary outcome measure will be safety, ensuring the cells graft properly and do not result in any tumorous growth.
Our secondary outcome measure will be efficacy. We will use a number of methods including PET imaging, UPDRS scores, wearable devices and more, to determine the effect of the transplants.
Will future trials use induced pluripotent stem cells(iPSCs) instead of embryonic stem cells?
We are looking into iPSCs for future trials, however they will not be individual cell lines, nor will we use a bank of match-able cell lines as other labs have proposed. Rather we are exploring a third solution where we modify the cells to create universal cell lines that can be transplanted into large cohorts of patients. The modifications will also eliminate the need for immune-suppression.
Ideally when would phase 2 trials start?
We believe it will take 9 months to implant all of the patients, then we will need to follow each for at least 12 months. Meaning it will likely take just under 2 years after we begin the phase 1 trials to move to phase 2.
What will be the role of Blue Rock Therapeutics?
Blue Rock Therapeutics is funding the trials and will help create the cell lines. If the trials are successful they will enable us to bring the therapy to market, allowing us to deliver it to thousands of patients.
Is there anything else you would like people with PD to know about cell replacement therapy?
Try to understand the principles, you don’t need to become an expert but you should understand what separates the good trials from the bad. For instance, the trials underway in China and Australia use neural progenitor cells that can grow to become a variety of different cell types. However, the trials proposed by the GForce-PD replace the lost cells with the same cell type.
Also, it is important to stress that this will not be a miracle cure, and any person or lab promising a cure should be avoided. We are still in the early stages of this therapy and over time the technique will continue to improve.
Besides stem cell research, what do you think are the most promising branches of PD research?
There is a lot of interesting research going on into understanding the disease process, particularly the role of non-neuronal cells like microglia.
We should also hear soon from the Novartis trial which will give us some indication as to the potential for alpha-synuclein antibodies. Gene therapy to promote dopamine conversion is another interesting avenue.
But I don’t think any of the current strategies will produce a clear winner because we still don’t have a good enough understanding of the underlying mechanisms. However, the next 5 years will see great improvements in our understanding of the biology which will lead to better therapeutic targets. Also using iPS cells to make better models of the disease will go a long way towards helping us design more effective therapies.
Further down the road I see a lot of potential for us to be able to change the age-related behavior of cells. Cells must age for the disease to happen but we might be able to rejuvenate the cells themselves using targeted therapies and intervention techniques that are only now beginning to be developed.