Remembrance of Things Past: Fetal Tissue Transplantation and Parkinson’s Disease

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In a recent article in Science magazine, Constance Holden reports that European researchers are contemplating a revival of fetal tissue transplantation for the treatment of Parkinson’s disease. As the article recounts, fetal transplants were subjected to sham controlled studies in the late 1990s; none performed better than sham, and several caused disabling dyskinesias. So should fetal tissue transplantation be revived, and if so, how?


The challenges seem all the more formidable today. We now understand that Parkinson’s disease is not restricted to the dopaminergic neurons in the basal ganglia, but instead involves diffuse pathology. And yet, studies will not involve implantation of tissues throughout the brain. As Holden’s article points out, previous fetal transplant studies revealed that brain pathology spreads to implanted tissues, suggesting that permanent responses may be difficult to achieve.

The ethical issues seem just as daunting. Deep brain stimulation has greatly improved the management of Parkinson’s for patients who are no longer responding to dopamine replacement. And yet, those pursuing fetal tissue transplantation will likely advocate pursuing trials in younger patients with less advanced disease. As pointed out by a European team of researchers, “A significant effort of bioethical research and conceptual clarification is required in anticipation of the first protocols involving human subjects.” And in a recently published article in Movement Disorders, several coauthors and I outline various ethical challenges presented by such studies. These include a high degree of uncertainty about the safety of interventions, and a baseline risk associated with delivery that approaches levels of risk encountered in phase 1 cancer trials (for studies that involve eight inoculations to the brain, risk of intracerebral brain hemorrhage leading to permanent neurological deficits is on the order of 2%).

Advocates of the new wave of studies insist we know much more about the properties of fetal tissues than we did in the 1990s; they further note that such studies will provide a basis for later studies involving induced pluripotent stem cells and other tissues. Perhaps, but given the remaining uncertainties and promise of DBS, it’s hard to imagine how fetal graft experiments could credibly establish a claim of clinical equipoise with deep brain stimulation. For these reasons, a more prudent ethical course—if fetal transplant studies for Parkinson’s are to be done at all—would be to pursue safety and feasibility studies in patients who are no longer responsive to standard care. Only once parameters are optimized and mechanisms well understood should clinicians consider studies in patients who are earlier in the disease process. (photo credit: Ethan Hein 2008)

BibTeX

@Manual{stream2009-82,
    title = {Remembrance of Things Past: Fetal Tissue Transplantation and Parkinson’s Disease},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2009,
    month = oct,
    day = 29,
    url = {http://www.translationalethics.com/2009/10/29/remembrance-of-things-past-fetal-tissue-transplantation-and-parkinsons-disease/}
}

MLA

Jonathan Kimmelman. "Remembrance of Things Past: Fetal Tissue Transplantation and Parkinson’s Disease" Web blog post. STREAM research. 29 Oct 2009. Web. 21 Oct 2020. <http://www.translationalethics.com/2009/10/29/remembrance-of-things-past-fetal-tissue-transplantation-and-parkinsons-disease/>

APA

Jonathan Kimmelman. (2009, Oct 29). Remembrance of Things Past: Fetal Tissue Transplantation and Parkinson’s Disease [Web log post]. Retrieved from http://www.translationalethics.com/2009/10/29/remembrance-of-things-past-fetal-tissue-transplantation-and-parkinsons-disease/


NOTES from the Underground

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Surgical innovation has always been a problem for medical ethics.  Surgeries are unregulated, and partly as a result, few are introduced to clinical practice having been validated in randomized controlled trials. Moreover, attempts at novel surgeries typically fly beneath the radar of ethical review, because they are viewed as innovative clinical practice rather than research. There are some good–and not so good– reasons for such “surgical exceptionalism.”


On Sunday, the Washington Post ran a story (“Scarless Surgery Uses Body’s Own Openings,” Rob Stein, Sept 21) on a new type of surgery, Natural Orifice Transluminal Endoscopy (NOTES), which avoids skin incisions by accessing organs through the mouth, anus, or vagina. Various teams are testing and/or using NOTES to remove gall bladder stones, to perform appendectomies and cholecystectomies, and to collect tumor tissue for cancer staging.

NOTES has the potential to reduce pain and scarring, and to hasten recovery. But the technique still requires validation in animal models. One major concern is infection: NOTES requires incisions through flora-rich environments like the rectum, stomach, or vagina.

Several U.S. and European medical societies have established initiatives aimed at guiding development of this technique. One example is NOSCAR (www.noscar.org), which maintains an outcome registry and identifies unmet research needs. The group also urges surgeons to seek independent ethics review before attempting NOTES in humans.

However, many first tries at NOTES have been performed outside traditional centers of medical innovation. For instance, the first team to perform a NOTES appendectomy is based in Hyderabad, India; several surgical teams in Brazil are also publishing a disproportionately large volume of human case reports (the prominence of Latin America and Asia is briefly NOTEd in the Washington Post story). One searches far and wide for any commentary on this phenomenon. Why are Brazil and India at the vanguard of surgical innovation? Is this simply one manifestation of the knowledge economy moving overseas? Or does it have something to do with laxer regulations and safety standards? Are there characteristics of NOTES that make it particularly attractive for surgeons working in resource-limited circumstances? (photo credit: photosan0, Pink Floyd album, 2006)

BibTeX

@Manual{stream2008-135,
    title = {NOTES from the Underground},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = sep,
    day = 22,
    url = {http://www.translationalethics.com/2008/09/22/notes-from-the-underground/}
}

MLA

Jonathan Kimmelman. "NOTES from the Underground" Web blog post. STREAM research. 22 Sep 2008. Web. 21 Oct 2020. <http://www.translationalethics.com/2008/09/22/notes-from-the-underground/>

APA

Jonathan Kimmelman. (2008, Sep 22). NOTES from the Underground [Web log post]. Retrieved from http://www.translationalethics.com/2008/09/22/notes-from-the-underground/


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