Stem Cell Report – Spring 2002

Date: 05/02/2002

In Humans

Treating Parkinson’s with Adult Stems Cell and Other Alternatives

Using adult neural stem cells, Dr. Michel Levesque, at the Cedars-Sinai Medical Center in Los Angeles, reports a total reversal of symptoms in the first Parkinson’s patient treated. The patient, a 57-year old former fighter pilot, is still without symptoms three years after the adult neural stem cells were removed from his brain, coaxed into becoming dopamine-producing cells, and then reimplanted. Because the stem cells came from the patient, there was no need for immunosuppression to overcome rejection. “I think transplantation of the patient’s own neural stem cells and differentiated dopaminergic neurons is more biologically and physiologically compatible – more efficacious and more elegant,” said Levesque. In addition to its use for Parkinson’s, the technique is under study for juvenile diabetes, stroke, brain tumors, spinal cord injury, and other conditions.1

Retinal Cell Implants Improve Parkinson’s

A team at Emory University School of Medicine has shown that implanting retinal cells into the brains of people with advanced Parkinson’s disease can improve motor function by almost half, according to a follow-up study of six patients. The team noted: “We’ve been following these six participants for over a year, and we’ve found they’ve improved, on average, nearly 50 per cent in motor function.” The retinal cells used were taken from deceased donors and grown in the lab. The team is not using immunosuppressantss2

In Animals

Stimulating Adult Brain Stem Cells Decreases Parkinson’s Symptoms

Injection of growth protein into brains of Parkinson’s rats caused their neural stem cells to grow, migrate to the site of damage, and begin to replace missing nerve cells. Eighty percent (80%) of the rats received a benefit from the treatment, with no tumor formation.3

Progenitor Cells Reverse Severe Parkinson’s Symptoms in Rats

Researchers at Chicago’s Rush University report coaxing progenitor cells from the brains of rats into becoming dopamine neurons to treat Parkinson’s disease. Led by Paul Carvey, the team discovered an important “shortcut” to creating a more efficient, more reliable, and safer source of stem cells with the ability to turn into specific neurons or brain cells. This study is the first to identify the signal that instructs stem/progenitor cells to become dopamine neurons. The researchers watched the cells develop, and selected and grew cells that were close to becoming neurons. They then grafted the cells into brains of Parkinson’s rats, effectively curing the animals’ severe Parkinson symptoms. The ability to select and grow large numbers of adult stem cells that would become neurons also has the potential to revolutionize the treatment of Alzheimer’s disease, multiple sclerosis and numerous other diseases and disorders of the brain and nervous system.4

Note: In contrast to these animal studies using adult stem cells, a widely publicized study showed just over 50% of Parkinson’s rats injected with mouse embryonic stem cells receiving a modest benefit, but one-fifth (20%) of the rats died of brain tumors caused by the embryonic stem cells.5

Gene Therapies Treat Parkinson’s in Rats, Monkeys

The injection of two corrective genes into a specific brain region generated significant restoration of normal limb movement in rats with Parkinson’s disease. Limb impairments were completely reversed in rats that had near-total Parkinsonian lesions on only one side of the brain, meaning that some of their dopamine-producing cells remained intact. But even in the rats with complete destruction of dopamine-producing cells, the delivery of gene therapy resulted in a limited amount of restored motor function. “We anticipate gene therapy will offer a way to help patients with Parkinson’s disease live many years longer free of disabling symptoms,” the researchers noted.6

A Japanese research team has demonstrated delayed delivery of gene therapy can provide significant recovery from Parkinson’s symptoms. Four weeks after inducing Parkinson’s damage in their brains, rats were given an injection of a gene vector which produced a growth protein call “glial cell line-derived neurotrophic factor” (GDNF). The animals showed remarkably higher levels of dopamine secretion and significant behavioral recovery, even up to 20 weeks following the injection.7

Treatment with three gene therapy vectors has shown behavioral recovery in Parkinson’s monkeys. The treatment resulted in remarkable improvement in manual dexterity and restoration of motor functions, with the behavioral recovery persisting for over 10 months in one case. The scientists say that this triple gene therapy method may offer a potential herapeutic strategy for Parkinson’s disease.8

  1. Results presented April 8th, at the meeting of the American Association of Neurological Surgeons.
  2. Result presented April 18 at the annual conference of the American Academy of Neurology in Denver and reported in the New Scientist , April 18, 2002. Note: There are no clinical treatments for Parkinson’s based on cloning or embryonic stem cells.
  3. J. Fallon et al.; “In vivo induction of massive proliferation,directed migration, and differentiation of neural cells in the adult mammalian brain,” Proc. Natl. Acad. Sci. USA 97, 14686-14691; December 19, 2000.
  4. Results reported at the Experimental Biology Meeting in New Orleans, April 2002.
  5. L.M. Bjorklund et al.; “Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model,” Proc. Natl. Acad. Sci. USA 99, 2344-2349; Feb 19, 2002 (published online Jan 8, 2002).
  6. D. Kirik et al.; “Reversal of motor impairments in parkinsonian rats by continuous intrastriatal delivery of L-dopa using rAAV-mediated gene transfer,” Proceedings of the National Academy of Sciences USA 99, 4708-4713; April 2, 2002.
  7. L. Wang et al.; “Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson’s disease,” Gene Therapy 9, 381-389; March 2002.
  8. S. Muramatsu et al.; “Behavioral recovery in a primate model of Parkinson’s disease by triple transduction of striatal cells with adeno-associated viral vectors expressing dopamine-synthesizing enzymes,” Human Gene Therapy 13, 345-354; February 10, 2002.
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