Parkinson's Disease (PD) and Huntington's Disease (HD) are neurodegenerative diseases that are caused by malfunctions within the motor sector of the nervous system. These malfunctions, which are caused either by the surplus (as in HD) or absence (as in PD) of hormones, are a direct result of neural cell deterioration within the brain. PD and HD illustrate two very different behavioral patterns that are subsequently caused by two opposite and extreme biological abnormalities. Yet the common thread between the two conditions is that there are major mechanical predicaments arising between cellular connections within the brain. Thus, it is the occurrence of cell death that functions as a key link between these two very different diseases. And it is because of this commonality, that the most controversial experimental treatment for PD and HD, fetal transplant surgery, functions as a possible cure for both these diseases. (18). The cause of neurodegenerative diseases, like PD and HD, is basically a story of how abnormal chemical interactions result in motor problems. Generally speaking, the brain is the body's communication headquarters. It obtains a myriad of information from various parts of the sensory system and processes this information in an organized fashion. It then relays sensory input to different parts of the motor system. Such messages from the brain dictate specific muscular and behavioral patterns. (18).
Moreover, there are two particular areas of the brain that are specifically related to motor malfunctions: the substania nigra and the striatum (the caudate nucleus and the putamen). The cells of the nigra synapse with cells of the striatum, which serves as the controller of motor functions such as walking, balance, and muscular movement. Information from the nigra cells passes through the synapses with the aid of a specific hormone, dopamine, which is a significant chemical transmitter in the brain. Because the existence of dopamine is essential to the function of the substania nigra, it is also essential for the various muscular activities controlled by the striatum, such as walking, balance, etc. (16).
In Parkinson's Disease and Huntington's disease the nigra-striatum neural communication assemblage is severely hampered. PD results from a depletion in the amount of dopamine produced by the brain. At the onset of the disease, dopamine-secreting cells of the substania nigra, either because of genetic factors or environmental toxins, experience mass cell death. Thus, the nigra cells are unable to form synapses through which they secrete and relay dopamine to the striatum in a neural circuit within the basal ganglia (18).
HD, in contrast, is not a condition offset by the environment, as PD is thought to be. It is indeed a condition due to cell death in the brain (basal ganglia) but is caused by an abnormal gene that codes for a mutant protein called huntingtin. Huntingtin, thus, interferes with normal brain cell functions by causing a depletion in neural cellular energy and neural death (12)(9).
Another example of how HD can be described as being the opposite condition to PD, has to do with both behavioral and biological symptoms of the neurodegenerative diseases. As mentioned previously, the striatum is also a coordination center for chemical messengers. Therefore, in PD, when there is a decrease in dopamine levels, the striatum experiences a chemical imbalance (3). Since the basal ganglia plays a largely inhibitory role on the spinal motor centers, the loss of control of the nigra of the striatum as well as the disabilities of the striatum due to abnormal dopamine levels cause inhibition of muscular movements (18). Therefore, as a consequence of microscopic dysfunctions, macroscopic abnormalities arise. As an example, the symptoms associated with PD, are rigidity, tremors, slowness and/or no movement, loss of balance and other physical ailments (16) which also lead to psychological conditions like depression and stress (17).
Instead of being the result of a hyper-inhibitory response by the striatum, HuntingtonUs Disease is caused by the death of inhibitory striatum cells. In general, a hormone, called GABA, produced in the striatum regulates the levels of dopamine in the brain through an inhibitory relationship. But in HD, because of the death of GABA-producing cells in the stratum, there is an over production of dopamine. Therefore, the inhibitory check on the motor system of the body is weakened and the symptoms of HD become apparent (18). These symptoms include random muscular movements, difficulty in motor coordination (12) such as chorea (loss of bodily functions) (5 ), and loss of many psychological functions (18), such as dementia (memory loss) (5).
One of the possible but currently experimental treatments for both PD and HD is fetal neural transplantation. This surgical procedure is just as complicated as the diseases themselves. The biopsy entails taking precursors of adult basal ganglia cells from fetuses (several weeks old) and putting them into the caudate nucleus and putamen (divisions of the striatum) of patients. (7)
The theory behind the transplant is to allow fetal neurons to replace lost striatum cells by forming new synapses with existing recipient cells (in order to produce neurotransmitters (7)) or by directly connecting themselves into the basal ganglia circuit. For example, in PD, the transplanted fetal cells are a source of hormone producers and secretors. The cells simply replace the dead host cells and carry on the function of the degenerated cells. But in HD, the fetal precursor cells actually become integrated into the brain circuitry. These embryonic cells change the mechanical and anatomy of the damaged region of the brain. (15) (5)
Even the procedure and technique that is followed during the transplant surgery varies form PD to HD treatment. In PD patients, the fetal cells are directly injected into the brain in the form of a liquid suspension. But in HD, a more complex system of micrografting neurons is involved. In addition, there has been more experiments done on human subjects in PD research that there has been in HD experimental surgery. Discoveries and information about the effects of fetal transplants in HD research is mostly from animal models. Again, this inconsistency is because of the greater level of complexity of performing a transplant operation on a HD patient compared to a PD patient. (6) (4) (14) Needless to say, in both PD and HD research endeavors, there has been observable but gradual improvements in patients who have had transplant surgery, for the fetal cells need time to grow, differentiate and influence (either through chemical or physical interactions) surrounding host neurons, especially dopamine-receiving cells (11). Thus, taking precursors of normal dopamine-producing tissues of fetuses, and either putting them in a liquid suspension, and implanting them into the striatum (damaged parts of putamen and/or caudate nucleus) of a PD patient, or grafting them into a HD patient, has proven to be a promising surgical technique for the alleviation of neurodegenerative diseases (1) (13)(6).
Fetal neural transplantation is deemed as a possible treatment for both PD and HD, two very different conditions, because it solves a common problem that is present in all neurodegenerative diseases. Cell death in both PD and HD may be caused by different factors but it can be treated or cured by one single technique. Thus, transplant surgery works for both PD and HD patients because it is a procedure that fixes cell degeneration. Even the behavior of the fetal cells, once within the host brain, varies. But the end result (the fact that the differentiability of fetal cells stops cell death to a certain degree in both these diseases) is the very similar. (2) (7)
Reflecting on all of the observations above, it is pertinent to form a general set of conclusions about the great potential of the brain and embryonic neural tissues. Indeed, the brain can be a regenerative organ, if put under the right conditions. In the case of fetal neural transplantation, primordial cells from embryonic tissues resulted in a rejuvenation of the damaged nigra and striatum. Also, one cannot help but be in awe of the ability of fetal neural cells to, as in HD, alter the whole structure of already differentiated and damaged adult putamen cells. There are many properties of fetal cells that allow them to act as neural repairers. Embryonic tissues proliferate fast, are able to travel to different regions of the brain, and also able to be very adjustable to different conditions. Thus, they are able to make connections with different types of host cells and adapt well to host environments. (8) (10)
Web Articles:
1. A Comparison of Neurosurgical Procedures
2. Advances in Understanding of the Disease Mechanisms
3. American Academy of Neurobiology
5. Brain Disorder Treatment Hailed
6. Early Postoperative Results in Ten Huntington's Disease Patients
7. Fetal Nerve Cell Transplantation
8. Fetal Tissue Transplantation
11. Neural Transplantation for Huntington's Disease
12. Neurosurgical Horizons in the Treatment of Huntington's Disease
13. NeurotransplantationUs Latest Stab at Incurable Brain Disease
17. Young Parkinson's Handbook
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