we have the same type of cellular destruction as does Cancer...
it is called apoptosis -


Harnessing the Power of Programmed Cell Suicide

By Erica Heilman


Human genes act as the body's blueprint, with coded instructions that tell each and every cell how to behave. But just as certain genes determine the trajectory of a cell's life, others carry instructions that determine its death. These 'suicide genes' create proteins that actually command cells to die. This natural process of cellular hari-kari, called apoptosis, actually helps to maintain the right balance of cellular function in the body, and suppression or acceleration of programmed cell death can be a recipe for disaster. For instance, cancer is the result of reckless growth and replication among certain cells, and it has been suggested that premature cell death may play a role in some neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease.

Understanding the secrets of programmed cell death could enable scientists to develop drugs to fight these diseases. Below, Dr. Dalton Dietrich, Scientific Director of the Miami Project to Cure Paralysis at the University of Miami, offers a brief introduction to the intricacies of apoptosis, and the potential power of controlling it in neurodegenerative disease.

How do cells die?
We used to think that cells just died as the direct result of injury. Now we know that cells actually carry genes that encode proteins that bring about their own death, like suicide genes, suicide proteins. This self-programmed cell death is called 'apoptosis.'

How does this happen?
In normal development of the central nervous system, we have too many cells. So there needs to be a mechanism to do away with the cells that are not needed. Programmed cell death, or apoptosis, during development of the spinal cord and the brain, ensures that there are not too many cells in the central nervous system.

Scientists now believe that these same suicide processes are reactivated in the adult brain and spinal cord after injury. So we're going back to normal neuronal development and targeting these processes that once were important in normal development of the central nervous system, and now appear to be important in cell death mechanisms in adult tissues.

How could this information be used to fight neurodegenerative diseases like Parkinson's disease?
Well it's important because we can develop new therapies to target that cell death mechanism. If we can get evidence of very early neurological problems in patients, we can treat them with agents that actually target and stop this programmed cell death. If we can block these processes, hopefully we can save the cell and protect the patient from chronic neurological disorder.

How much progress have we made already?
We are pretty far along in terms of the progress targeting suicide proteins and programmed cell death. In our experimental models, we have a good idea of what enzymes are activated. We understand the biochemistry of the pathways. And we are now developing new drugs that can be given to patients with these types of problems.

Clinical trials are now being introduced in the United States to use some of these new inhibitors of apoptosis. For example, in patients with acute stroke, scientists are thinking about combining thrombolytic treatments that improve perfusion in the brain with these anti-apoptotic agents to salvage the brain tissue.

What role might apoptosis play in Parkinson's disease?
In Parkinson's patients, we believe there's a slow death of dopamine-producing neurons in the brain. One hypothesis is that these neurons are dying by apoptosis, or are undergoing a kind of 'death by suicide.' Now, if that's the case, when the patient has early signs of neurological problems, it is possible that one day we could give that patient a type of drug that targets apoptotic cell death and could stop the progression of the disease.

This type of therapy has not been tried on patients because we're still trying to understand how to target patients in the very early stages of Parkinson's disease. And more basic research needs to be conducted before the drugs are powerful enough to actually stop this cell death process.

How far are we from making this hypothesis a reality?
We need to continue to study neurodegenerative diseases, and determine what is the window in which these drugs could be given. When a cell starts to die, it may take a period of time. And we have to understand how early we have to give the drug in order to stop the cell death permanently.

Are you excited by the potential of this treatment idea?
This is going to be a very exciting development in the treatment of acute neurodegenerative diseases, as well as diseases associated with acute trauma.

Already there are various approaches that we're using in patients with acute spinal cord injury, for example to delay cell death or prevent cell death. We're utilizing drugs that are already available that target various mechanisms of cell death including apoptosis. But more work needs to be done to define the mechanisms that need to be targeted. And therefore, more development with pharmaceutical companies and biotech companies is currently being carried out to produce new-generation drugs that can limit this cell death.

Published on: January 24, 2003

http://www.advancesinneurology.com/