Biomedical Engineering Reference
In-Depth Information
to transplant stem cells into the brain. Based on the promising findings in mice, the
Alzheimer's Drug Discovery Foundation is funding a pilot clinical trial at USF's
Byrd Alzheimer's Center. The randomized, controlled trial, led by Dr. Sanchez-
Ramos and Dr. Ashok Raj, will test the safety and effectiveness of filgrastim in 12
patients with mild-to-moderate Alzheimer's disease.
Parkinson's Disease and Stem Cell Therapy
Parkinson's disease is the second most common neurodegenerative disease following
Alzheimer's. Approximately 1.5 million people in the USA suffer from Parkinson's
disease, which is caused when 80% or more of dopamine-producing neurons in the
substantia nigra of the brain die. Normally, dopamine is secreted from the substantia
nigra and transmitted to another part of the midbrain. This allows body movements
to be smooth and coordinated.
The main pathology in PD is degeneration of nigrostriatal dopaminergic neu-
rons. The predominant neuropathological feature of Parkinson's disease is charac-
terized by a loss of the neuromelanin-containing dopaminergic cells of the substantia
nigra. It seems, however, not the primary loss of these cells themselves that is the
fundamental pathology, but the consequent loss of their neurotransmitter, dopamine.
The eventual result is a degeneration of the complete dopaminergic nigrostriatal
pathway, although it is estimated that 80% of dopamine in the striatum is lost before
symptoms become clinically apparent ( http://www.parkinson.org/site/pp.
asp?c=9dJFJLPwB&b=71125 ) . At post-mortem, physiological deterioration is also
observed in areas of the brainstem such as the nuclei of the locus coeruleus and the
dorsal motor nucleus of the vagus. Lewy bodies (eosinophilic intracytoplasmic
inclusions) are found in the brainstem and other parts of the brain, and are diagnostic
of the condition, at least at post-mortem.
Patients with Parkinson's disease are treated with the drug levodopa (or L -dopa),
which is converted to dopamine in the body. Initially effective, the treatment's
success is reduced over time and side effects increase, leaving the patient helpless
( http://stemcells.nih.gov/info/scireport/chapter8.asp ) . It has been recognized that
dopamine-producing cells are required to reverse Parkinson's disease. Since the
1970s, many types of dopamine-producing cells have been used for transplantation.
These include adrenal glands from the patient, human fetal tissue, and fetal tissue
from pigs [ 53 ]. Limited success has been achieved with these cells. Rat and monkey
models of Parkinson's were used to test fetal mesencephalic cells [ 54, 55 ] . Success
with animal models led to clinical trials.
Trials with human fetal mesencephalic tissue reach in postmitotic dopaminergic
neurons have provided a proof of principle that neuronal replacement can work in
human brain. They reversed the impairment of cortical activation underlying aki-
nesia. Several open-label trials have reported clinical benefits [ 54, 55 ] .
Unfortunately, dyskynesias can develop after transplantation and become trouble-
some in 7-15% patients [ 56, 57 ]. These adverse effects are not due to dopaminergic
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