Neurodegenerative Diseases and Neurogenesis
A major development in the treatment of neurodegenerative diseases
such as Parkinson's and Huntington's has been the transplant of
embryonic stem cells as a form of treatment. However, this approach has
problems associated with it, including ethical and technical concerns.
Studies have found endogenous stem-progenitor cells in the
hippocampus and the subependymal layer (SEL) of the basal ganglia in
the adult brain, which may offer a possibility that
these cells could be able to generate neurons for cell
replacement therapies in neurodegenerative diseases, reducing the need
for embryonic stem cells. (4)
Huntington's Disease
A recent study conducted by Curtis and colleagues used postmortem
brain tissue from Huntington's Disease patients in
order to examine whether neurogenesis occurs in the SEL region located
beside
the caudate nucleus in the brain where cell death has occurred. The
results of this study showed that neurogenesis
occurred in these areas, showing that the brain has the ability to
repair itself. The researchers are not clear which factors caused the
growth of the cells, and the increase was not large enough to
compensate
for the high levels of cell death in Huntington's patients. The hope is
that the level of cell growth could be increased through growth factors
or pharmaceuticals,
to develop an effective treatment for neurological disease. (3)
Alzheimer's Disease
Neurogenesis could also be useful in the treatment of Alzheimer's disease. Studies have been conducted on mice focusing on the gene Presenilin-1 (PSI), which is found in both mice and humans. Mutations in this gene are often found in humans that have early onset Alzheimer's. PSI works by encoding a protein in brain cells located in the hippocampus and other brain regions that control memory and learning. Joe Tsien and colleagues deleted PSI from the mouse brains, then put the mice into an environment where they were subjected to a number of tests to aid memory and learning. They found that the mice that had the PSI gene deleted formed less nerve cells after being in a stimulating environment, which suggests that PSI is a major factor in neurogenesis. The mice without PSI seemed to recall more information at first, but had problems clearing out memories copied in the cortex. Tsien suggested that the mice's brains may become "overloaded" and therefore it will become difficult for the mice to form long-term memories. This shows a similarity to the problems that Alzheimer's sufferers face, since in the early stages of the disease people have difficulty forming long-term memories. These findings may also help to explain the problems that researchers have had with insertion of stem cells, since it is possible that the new neurons could erase memories.(10)
Treatment Concerns
There are a number of concerns that researchers will need to address once neurogenesis-enabling treatments become available. Among these include:
- Possible modification of a person's central nervous system
- Moral issues concerning the source of stem cells (embryos)
- Future possiblity of over-population (as a result of life extension)
- Safety of procedures
- Ensuring all humanity benefits from these treatments (including developing countries and non-technocratic elite)
- Informed consent in cases where the individual's disease is in an advanced stage