Mr NN had just returned from “La Plaza de los Mariachis”, and his wife was preparing dinner. They were talking about about the decreasing number of customers requiring his services as a mariachi. The table was set when Mr NN, an obese 62-year old man with hypertension and diabetes, asked his wife to open the window, feeling the room grow hot and suffocating. That day was unusual; normally, Mr NN comes back from work singing and whistling his favourite songs, but that night he just sat at the table for dinner, hoping to feel better after eating. He had hardly tasted his food when he started seeing double. Everything was spinning round, and his speech was incomprehensible. Mr NN arrived during the night to A&E complaining of vertigo, nausea and gait disturbances and, having lost the capacity to speak fluently and clearly due to dysarthria. After a few days, the diagnosis of a brain stem stroke has determined that less than 20 millimetres of brain damage has stolen Mr NN’s musical voice forever.
Mr NN’s speech disorder reminds us that neurological diseases are one of the most important causes of disability worldwide and have a big effect on the ability of patients to manage their lives on a day-to-day basis, varying widely in the level of disability they cause; the effectiveness of pharmacological or surgical treatments is equally variable. For example, people affected by Parkinson’s disease (PD) have a relatively normal life expectancy, as several drugs are helpful during the first 3-5 years of the disease. Unlike PD, amyotrophic lateral sclerosis (ALS) has no treatment and causes a fast death. The treatments of other neurological conditions, such as multiple sclerosis, brain and spinal cord traumas, and stroke, have different degrees of effectiveness in preventing disability.
Stem cell-based therapies for neurological conditions have recently become popular as one of the most promising therapies for repairing the central nervous system. Different sources of stem cells can be used, including human embryonic stem cells, induced pluripotent stem cells and neural stem cells. Currently, there is no specific stem cell therapy approved for treating neurological disorders and several universities and health companies around the world are working to convert this promising research into clinical cell therapies.
Regenerative neurology (ReN), a branch of regenerative medicine, has the potential to significantly impact neurological treatments, through the explanation of the disease’s neuropathogenesis, the acceleration of drug discovery and the direct transplantation of stem cells. Professor Siddhartan Chandran at University of Edinburgh is working in this emerging discipline. His laboratory is trying to develop stem cell therapies that can protect the healthy neurons inside the brain, combining disease modelling and clinical trials. Disease modelling allows scientists to investigate how neurological disorders work in the laboratory, by mimicking human diseases in animal models or cells in a dish. Stem cells can self-renew and differentiate into specialised cells, including brain cells, and could be used to generate brain tissue to study the progress of the disease or the effect of some drugs into the nervous system. Besides, studying the diseases in petri dishes might help minimise the use of animal models and create a better disease model by using human cells.
The direct transplantation of stem cells into the nervous system is another alternative, although biological, clinical, and safety considerations must be taken into account before proceeding with any cell therapy. Some experiences have been translated to the clinic, specially in patients with Parkinson’s disease (PD). The first clinical trials in PD were performed in Sweden (Lindvall, 1989), and then in Mexico (Madrazo et al., 1990). These patients were transplanted with foetal midbrain tissue. Since then, hundreds of patients around the world haven been transplanted with foetal mesencephalic tissue (Barker 2010).The results have been very variable, but in some cases cells did engraft and showed functional integration, giving the patients a degree of symptomatic relief. Based in these promising results, Professor Roger Barker, at University of Cambridge, is testing foetal neural stem cells in patients with PD. They are currently performing clinical trials with foetal ventral mesencephalic transplants, in order to show that the replacement of the lost dopaminergic cells with neural stem cells can clinically work in patients. This approach is literally trying to repair the small part of the midbrain called substantia nigra through the replacement of new cells that are able to generate dopamine (substance whose lack causes PD’s symptoms).
The proper and ethical use of stem cells can benefit the one billion of people who are affected by neurological diseases worldwide (World Health Organization, 2006). Therefore, it is extremely important to translate all research findings to clinically proven treatments. Unfortunately, there are private stem cell banks around the world offering unproven and dangerous stem cell treatments for various medical and neurological diseases, exploiting the patients’ hope and desperation for profit.
In conclusion, treating neurological diseases remains a major challenge in medicine. Stem cells can be used to fight off neurological disabilities and offer neurological patients a better quality of life. However, hopes that brain damage and Mr NN’s singing voice can be repaired by these novel therapies, are still limited to those small petri dishes.