Are iPS cells the answer to ALS?

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive and fatal disorder in which motor neurons are degraded. Motor neurons are involved in processes such like movement, breathing, eating and speech. Currently there is no cure for ALS and patients diagnosed with this disease typically die within three to five years following the presence of symptoms. In 2014 the awareness of this disease increased with the Ice-Bucket challenge that arose on social media, causing millions of people to donate money to research for possible treatment methods. In the meantime scientists have spent a lot of time researching this disease to find possible treatment methods.

One of a very promising treatment methods targeting the neurons degraded in ALS method involves the use of stem cells. Stem cells are the specific cells involved in the development of a fertilized egg to a baby. These cells have the ability to become any of the cells composing a human body, an ability called pluripotency. Once these cells mature and form the human body they lose their pluripotency and can either become multipotent or unipotent (figure 1). Multipotent means that the cells can only form cells from related tissues, for example a multipotent blood stem cell can form white blood cells and red blood cells. Unipotent means that the cells can only become 1 specific cell type, for example a unipotent skin stem cell will only form skin cells. Pluripotent stem cells are found in embryos (where they are called embryonic stem cells) and cannot be found in a body after it has developed. However, due to a lot of ethical and medical reasons these embryonic stem cells are not used in therapy.  

Figure 1. The potency or state of stem cells during differentiation.

Since stem cells seemed like a promising treatment for ALS, scientists decided to search for alternatives for embryonic stem cells. They found this in the form of induced pluripotent stem cells (iPS cells). iPS cells are cells which are removed from the human body, like skin cells, and grown in a Petri dish. These cells are next treated with specific proteins called reprogramming factors that cause these cells to become pluripotent like the embryonic stem cells. Finally, these iPS cells can then be treated with other proteins and, with input from the environment they are in, these cells can then become a specific type of tissue. This method makes it possible to remove skin cells and treat them to become iPS cells and finally be induced to become red blood cells.

But how is all of this relevant to ALS? Scientist took skin cells from willing ALS patients and used reprogramming factors to turn them into iPS cells. After they managed this, they reprogrammed these iPS cells to form motor neurons, which are degraded in ALS (figure 2). These scientists also noted that the formation of iPS cells was completely independent of how far progressed the disease was or the age of the patient. This study opened several ways of progress in the study of possible treatment methods for this degenerative and deadly disease.

Figure 2. The induction of skin cells to become iPS cells which, in turn, are induced to become motor neurons

One of these progresses is that this particular study make showed that reprogramming of skin cells to motor neurons is possible. By reprogramming skin cells to become motor neurons scientists can have an unlimited source of cells to study the disease and find possible treatment methods. Furthermore, research performed on human derived cells will give a more accurate representation which could lead to faster and more accurate results. This study also opened up the probability for cell transplantations for patients. Transplantations of organs, or in this case motor neurons, between 2 people has a high chance of rejection of the donor tissue by the patient’s body. This is due to the difference in DNA between the two people. Rejection of the donor tissue can lead to serious complications. By having a patient’s skin cells transformed to the motor neurons, the rejection of these cells by the body is lowered significantly since the DNA between the patient and the newly grown neurons is the same.

There is still a necessity for further research since these possible treatment methods are not yet possible with the current knowledge scientists have at the moment. One of the major struggles is to make these treatments safer for the patient and time and money efficient. But because of the fast progress scientists have been making over recent years, these methods might be designed soon. And who knows, maybe in the coming 10 years iPS cells will be the answer to curing ALS.

By Kate Feller. October 7, 2015