Are we ready to transplant new brain cells?
Researchers in Japan have published 2 groundbreaking studies into transplant therapies for Parkinson’s, and it has been predicted that clinical trials could start as early as 2018. We take a look at the science behind the headlines.
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Currently there are no treatments that can slow or stop the progression of Parkinson’s. In the condition, dopamine producing brain cells are gradually lost and, without this important chemical messenger, symptoms such as tremor and slowness of movement occur.
Replacing the cells that are lost in Parkinson’s has the potential to reverse these symptoms, the major hurdle is where to find or how to produce the right cells for transplantation.
Scientists have been interesting in the potential of stem cells to make new brain cells for Parkinson’s for some time. And, more recently, have developed ways to turn normal adult cells, such as skin cells, into stem cells (called induced pluripotent stem cells or iPSc for short). From there, these stem cells can be turned into the type of dopamine producing brain cells lost in the condition.
You can read more about this in a previous post:
So what do these new research studies add to our growing understanding of the potential of cell therapies for Parkinson’s?
Reversing the motor symptoms of Parkinson’s
In the first study, published in Nature, the researchers transplanted new dopamine producing brain cells into a primate model of Parkinson’s. The aim was to build on previous studies in rodents and to see the effects in an animal model that is more closely related to humans.
Stem cells, created using normal blood and skin cells from a number of people affected by Parkinson’s and healthy subjects, were made into dopamine producing brain cells. These cells were then successfully transplanted and, over the next 12 months, gradually improved movement in these primates.
To test how the cells were behaving, the researchers used brain scans. They showed that the cells were functioning like normal dopamine-producing brain cells and were successfully producing dopamine. And later they were able to confirm the transplanted cells had indeed survived and, more importantly, had integrated with the existing neuronal network — becoming a functioning part of the primate brain.
They also noted that none of the new brain cells turned into cancerous cells, a problem which has previously hampered stem cell derived transplants.
Immunity and transplantation
Should human cell transplantation become a future therapy for Parkinson’s, one of the key considerations will be to avoid an immune response that could kill the newly transplanted cells.
Our immune system is designed to fend off foreign invaders like bacteria and viruses. It works by recognising our own cells and attacking anything that is not recognised as self. While this is vital for our health, it can be a challenge if you are attempting to treat someone by transplanting cells or organs from someone else.
Researchers first experimented with organ transplantation in the 18th century and, by the mid-20th century, successful organ transplants were being carried out. Today, many transplant surgeries are considered routine medical treatments.
Key to this progress has been the development of tissue typing and immunosuppressant drugs. Tissue typing is based on the Human leukocyte antigen (HLA) — a protein — or marker — found on most cells in your body. Your immune system uses HLA markers to know which cells belong in your body and which do not. This is not the same as ABO blood typing, and there are far more HLA types than blood types.
Today, improved in tissue typing and better immunosuppressant drugs allow more organ transplants to be successful, increase survival and extend the life of recipients.
Overcoming the immune response
In the first of these new studies, the researchers used immunosuppressants to prevent the new brain cells from being rejected. However, these drugs have a down side as they can leave people vulnerable to infection.
To overcome the issue of transplant rejection, and reduce the need for immunosuppressents, the second study from the same Japanese team (published in Nature Communications) successfully used the principles of matching for organ donation to select the best brain cells for transplantation.
For the first time, the researchers matched the HLA type of the brain cells — this time made from induced pluripotent stem cells from primates — to the recipient and successfully reduced the immune response to these transplants.
The potential of cell transplants therapies
The future of cell therapies for Parkinson’s looks very bright, and this new research is definitely a step in the right direction.
It would appear that we are able to make functioning brain cells that will survive and perform in the brain, and may reverse some of the symptoms of Parkinson’s. And we may be able to select the right brain cells for the right people, so reducing the need for immunosuppressants.
The methods that allow us to make our own stem cells from adult cells, also answer many of the ethical questions and resource requirements around using other sources of stem cells — such as human embryonic stem cells.
But it is not only Parkinson’s that would benefit from this type of therapy. Because of this, there has been much interest in developing infrastructure to support future cell based. But treating lots of different types of condition by replacing faulty cells with new ones will require many different types of cells.
While it may not be possible to have banks for all these types of cells, it is possible to bank stem cells that can be turned into the right cell to treat each person as needed. The stem cells in these banks will likely need to be matched to different immune types, much like organ donors are matched to transplant recipients.
There are many more HLA immune types than blood types, so it might sound like a daunting task to bank enough types of stem cell to cover an entire population’s needs. However, the Japanese researchers propose that a bank of stem cells for human transplantation could be created from just 150 donors, which would supply stem cells that could be matched to 93% of the UK population.
So what next?
David Dexter, our Deputy Director explains:
“Both of these studies represent an important development in the field of transplantation as a potential treatment for Parkinson’s. Current medication only serves to mask the symptoms of the condition, but makes no changes to the brain cells themselves. These studies show that, should brain cell transplantation become a viable therapy, it has the potential to reverse Parkinson’s by replacing the dopamine cells that have been lost — a groundbreaking feat.
“Although this is promising quality research, and the conclusions are backed up by solid data that comes from a variety of sources, including behavioural, brain scans and histological analysis, there are still major challenges ahead.
“We need to understand if these new transplanted cells would succumb to the same fate as the original cells that had previously died. There are also other types of brain cells that are affected by Parkinson’s and additional work must be done to tackle the symptoms of the condition that are not caused by a lack of dopamine.”
So there is more research needed. We do not know enough about how these transplant therapies may, or may not, benefit the non motor symptoms of Parkinson’s, such as problems with thinking, memory, anxiety and smell. And while the transplants seemed to be safe for 12 months, there are still concerns over the long term safety of these types of transplant.
Fortunately, there is a global effort to drive this area of research forward, and studies, such as this research funded by Parkinson’s UK will help to address the questions that remain:
It is only with the help of people like you that we can continue to fund cutting edge research and ensure that new and better treatments are delivered as quickly as possible. Help us speed up this process by donating to our work today.
