Here's more in the continuing saga:
------------------
Rat model of Parkinson's disease corrected by gene therapy, UW-Madison's
Jon Wolff reports
Researchers at UW Medical School and the Waisman Center on Mental
Retardation and Human Development have narrowed the search for a safe and
effective treatment for Parkinson's disease (PD). Using a unique form of
gene therapy developed at UW-Madison, they substantially and consistently
reduced symptoms of the disease in rats.
If successful in human patients, the technique may avoid serious problems
associated with existing treatments for Parkinson's, said Jon A. Wolff,
UW Medical School associate professor of pediatrics and medical genetics,
who directed the research. Clinical trials may begin this year, he added.
Wolff genetically engineered some rat muscle cells to express the enzyme
tyrosine hydroxylase, and then placed the cells inside the brains of
rats. In that location, the enzyme causes muscle cell's own chemistry to
produce L-DOPA, which alleviates the symptoms of Parkinson's disease, a
neurological disorder caused by the degeneration of certain brain cells.
Wolff noted that transformed cells had worked in that way before, but the
effects dropped off. In Wolff's latest research, published in the
journal Nature April 1, the beneficial effects persisted.
"The long-term ability of our muscle-cell gene transfer system to correct
symptoms of Parkinson's disease in rats makes it an attractive candidate
for treatment of the disease in humans," said Wolff, who also is
director of biochemical genetics at the Waisman Center. His collaborator
on the research was Shoushu Jiao, assistant scientist at the Waisman
Center.
Two years ago, Wolff gained national attention when he injected mouse
muscle cells with DNA, and produced long-term expression of the test
enzyme coded for by the DNA. Later, Wolff repeated the process with a
gene for dystrophin, the enzyme lacking in muscular dystrophy patients.
The Harvard Health Letter last year ranked his approach to gene therapy
in muscular dystrophy one of the top 10 medical achievements of 1991.
In his Parkinson research, Wolff postulated that the long-term enzyme
expression of muscle cells would make them effective producers of L-DOPA
in the brain. Both the muscle cells carrying the gene for tyrosine
hydroxylase, and control-group cells engineered to produce other marker
enzymes achieved expression in rat brains.
Rats used as research models for Parkinson's exhibit an "asymmetrical
rotational (staggering in circles)" behavior. Wolff successfully
demonstrated that rats exhibiting the rotational behavior before the gene
therapy procedure had greatly reduced expression of the behavior for up
to 24 weeks.
"The consistent ability of this muscle cell/gene transfer system to
promote high levels of intracerebral transgene expression and
substantially to reduce asymmetric rotational behavior in the rat PD
model makes it an attractive candidate for clinical application," Wolff
said.
In other words, if similar procedures were effective in humans, patients
suffering from Parkinson's could lead significantly better lives, with
less uncontrolled movements, for years after treatments. The treatment
also avoids ethical concerns that have been raised about the use of human
fetal cells as implants to relieve Parkinson's symptoms.
Research positions available
Jon Wolff is looking for both research technicians and post-doctoral
researchers to join his team. Contact Wolff at 608/263-5993.
.
-----------
Parkinson's disease in monozygotic twins.
Jankovic J; Reches A
Ann Neurol 19: 405-8 (1986)
Abstract
Recent studies of twins have demonstrated an unexpectedly low concordance
of Parkinson's disease in monozygotic twins. Only two monozygotic twin
pairs concordant for it have been reported. However, both pairs were
atypical because of an early age at onset and other unusual features. We
studied a monozygotic twin pair concordant for typical Parkinson's disease.
The brothers have lived apart for forty years. The onset of tremor occurred
three months apart, at age 71. The progression of the symptoms has been
identical. Although one of the twins is more severely affected, both have
typical manifestations of Parkinson's disease that respond well to
dopaminergic medication. The occurrence of Parkinson's disease in these
monozygotic twins suggests that genetic susceptibility is important in the
tremor-dominant variety of Parkinson's disease.
Mesh Headings
Aged
Antigens
Case Report
Diseases in Twins*
Erythrocytes
Human
HLA Antigens
Male
Parkinson Disease*
Phenotype
Twins*
Twins, Monozygotic*
Unique Identifier: 86213829
-------------
Variant cytochrome P450 CYP2D6 allelic frequencies in Parkinson's disease.
Kurth MC; Kurth JH
Division of Neurology, Barrow Neurological Institute, Phoenix, AZ 85013.
Am J Med Genet 48: 166-8 (1993)
Abstract
Aberrant detoxification of environmental agents may be the basis for an
inherited predisposition to Parkinson's disease. A CYP2D6 genetic marker of
the debrisoquine hydroxylase "poor metabolizer" phenotype was found to be
significantly increased in Parkinson's disease patients compared to
controls, as has been shown in previous studies. Presence of this marker
gives an odds ratio of 1.86 for Parkinson's disease (95% confidence
interval 1.33-2.39, P < 0.02). For comparison, a CYP1A1 polymorphism, which
is not known to be associated with aberrant drug metabolism, showed no
association with Parkinson's disease in our study.
Mesh Headings
Aged
Aged, 80 and over
Alleles*
Cytochrome P-450*
Gene Frequency*
Genetic Markers
Heterozygote
Homozygote
Human
Middle Age
Parkinson Disease*
Phenotype
Support, Non-U.S. Gov't
Variation (Genetics)*
Unique Identifier: 94121115
Chemical Identifiers (Names)
(Genetic Markers)
9035-51-2 (Cytochrome P-450)
----------
that's all folks... for now!
Wendy Tebay
