Sunday, May 17, 2009

Parkinson's Disease Stem Cell Sequel


By Amy Price PhD
I found an interesting addition to the Parkinson's post's in the form of an article from Nature. Many thanks from helpful individuals at the Open University in the UK for passing this on.

In the article in Nature Suchowersky O. Transplantation therapy for Parkinson disease: the good, the bad and the enigmatic. Nature clinical practice. Neurology. 2008 Sep;4(9):465
Parkinson disease (PD) affects an estimated 1 million cases in North America . Motor symptoms in PD initially
respond well to dopaminergic replacement medications, but because PD progresses the drugs gradually lose effectiveness after about 10 years resulting in gait dysfunction and complications such as dyskinesias
PD is not just a disorder of the dopaminergic system but involves other neurotransmitter systems which inform autonomic dysfunction, mood disorders, fatigue, pain, sleep disorders and cognitive function. Dopaminergic cell replacement, even if successful is thought capable of treating only motor symptoms.
Over 20 years ago, transplantation of fetal ventral mesencephalic cells into the putamen was
performed on a small sample of participants with reportedly good results. Regrettably further studies with larger participant pools failed to confirm the initial reports (Freed CR et al. [2001] N Engl
J Med 344: 710–719). PET and pathological analyses revealed adequate survival of grafted
neurons, and there was untreatable runaway dyskenesia. However clinical benefit was seen in
a small subset of patients, 16 years on autopsy results are available Mendez et al. showed survival of
grafts without PD pathology for 14 years in five patients (Mendez I et al. [2008] Nat Med14: 507–509). Another patient showed good clinical improvement l 5 years plus, before gradual worsening of motor function and development of gait and balance problems (Kordower JH et al. [2008] Nat Med 14: 504–506). Autopsy results from this patient 14 years after transplantation showed great graft survival but grafted neurons had pathological
changes typical of PD, including Lewy bodies and activated microglia (cell scavengers) were seen in large numbers
Liet al. reported similar graft pathology in three patients up to 16 years after transplantation (Li JY et al. [2008] Nat Med 14: 501–503). These results indicate that for stem cell therapy to be effectual long term in D research needs to be initiated to investigate the spread to youn grafted neurons and determine strategies to resolve this issue. I would hope that advancement in the area of Adult Stem Cell research will make this possible in the near future.

I am finding the stem cell story is not so new. I did hear about a very young women stricken with metasticized spinal cancer who was treated at Sloan Kettering with grown out adult stem cells taken from her own bone marrow over fifteen years ago. She is now a successful professional with no trace of malignancy in her body. I also remember twenty five years ago in Canada I knew three terminal patients who underwent adjustments to the bone marrow transplant protocol that involved growing out their own bone marrow cells. One person enjoyed a year free from blood cancer and then relapsed but the other two lived. It is strange that when I go to Pub Med , Google Scholar or even the University library there is no trace of this research performed for "humanitarian reasons"

There is also a lot of interest in the London Project where stem cell trials are close to human trials for those with macular degeneration. Pfizer is quoted as expected to announce backing of stem cell therapy, apparently with joint labs in Cambridge Mass and Cambridge UK but on the Pfizer site I didn't see this in place.

Individuals are reporting encouraging success for adult stem cell treatment where they are thier own donors particularly for orthopedic and cardiac applications. These treatments are largely privately funded. It would be great to see this in the mainstream covered by insurance and available for people regardless of income levels

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