This document addresses adrenal-brain, fetal mesencephalic and fetal xenograft transplantation, which have been proposed as treatments to modify the symptoms and disability of advanced Parkinson's disease.
Parkinson's disease is a progressive, incurable, disabling disease caused by slow continuous loss of nerve cells in a part of the brain called the substantia nigra that produces dopamine, a brain chemical critical for movement of the body. According to the National Institutes of Health (2011), approximately 1 to 2 percent of adults over the age of 60 are affected by Parkinson's disease.
Common symptoms of the disease include tremors or involuntary movement in the jaw and extremities, slowed movement, muscle stiffness, gradual loss of voluntary movement, gradual loss of automatic movement, postural instability and depression. The exact cause of Parkinson's disease is not known, but there is some evidence that there may be an inheritable component to the disease.
At this time, there is no known cure for Parkinson's disease. Primary management of the disease is through pharmacologic therapies. No drug has been shown to effectively slow the progression of the disease. As Parkinson's disease progresses, pharmacotherapy becomes less and less effective in managing the symptoms of the disease. Surgical procedures such as pallidotomy and electrical deep brain stimulation may be considered for severe cases. However, none of these treatments correct the underlying problem of nerve cell degeneration.
Several techniques have been proposed for the treatment of the underlying cause of Parkinson's disease, in which tissue or cells from other sources are transplanted onto the candidate's brain at the location where cell degeneration is occurring or in nearby areas. Theoretically, the transplanted cells take the place of the dysfunctional brain cells by producing dopamine, thus improving the signs and symptoms of Parkinson's disease.
The transplantation of tissue from the adrenal glands, specifically adrenal medullary tissue, to a portion of the brain called the corpus striatum, called adrenal-to-brain transplantation, is intended to improve the motor and postural dysfunctions of Parkinson's disease. Adrenal-to-brain transplantation can involve either an autograft from the candidate or an allograft from an aborted fetus. When done with the individual's own adrenal tissue, a complicated double surgery, one to remove the adrenal tissue, and one to transplant it into the brain, is required.
Another type of transplant for Parkinson's disease, fetal mesencephalic transplantation, involves a surgical procedure to implant tissue harvested from fetal brains, specifically mesencephalic tissue, into portions of the candidate's brain known as the caudate and putamen areas.
Finally, surgery to transplant brain tissue from fetal pigs (e.g., xenografts) into the brains of individuals with Parkinson's disease has also been attempted. The goal of this procedure, as with the other procedures described, is to implant dopamine-producing cells into the brain, alleviating the symptoms of the condition.
Adrenal-to-brain transplantation with autograft or fetal allograft is considered INVESTIGATIONAL in all cases.
Fetal mesencephalic transplantation for the treatment of Parkinson's disease is considered INVESTIGATIONAL.
Transplantation with fetal xenografts (e.g., from pigs or other animals) for the treatment of Parkinson's disease is considered INVESTIGATIONAL.
Parkinson's disease is a motor system disorder resulting from the loss of dopamine-producing cells in the midbrain that innervate the caudate and putamen. Symptoms include resting tremor, rigidity and the impaired ability to start and continue bodily movements. Because pharmacologic treatment does not provide sufficient long-term therapeutic benefit, surgical interventions to transplant dopamine-producing tissues into the brain are under study.
However, at this time, the medical literature regarding adrenal-to-brain transplantation for the treatment of Parkinson's disease is limited to the description of uncontrolled, short-term studies with small sample sizes or case studies. Although some of these studies did report finding significant clinical improvements, unreasonably high morbidity and mortality rates are frequent. A few pathologic reports on adrenal-to-brain recipients demonstrated very few to no surviving transplanted cells after six months to a year following surgery. Due to the lack of long-term outcome data from large controlled randomized trials and reports of high rates of complications and death in the existing literature, studies investigating adrenal-to-brain transplantation for the treatment of Parkinson's disease have diminished.
The evidence for fetal mesencephalic transplantation is more promising than that for adrenal-to-brain procedures. However, the existing body of literature is still inadequate to allow conclusions regarding this procedure. Concerns related to small sample sizes and a limited number of controlled trials are joined with a wide array of methodological issues with the procedure itself.
The medical literature currently describes several different surgical approaches, either open or stereotactic, and bilateral vs. unilateral, along with several different tissue preparation methods, variation in the number of transplants, inclusion or exclusion of postoperative immunosuppressive therapy and the type of screening used for tissue donors. Concerns about methodology aside, the existing evidence for this type of procedure demonstrates low morbidity and mortality, significant improvements in short- and long-term physical symptoms, and graft viability and function is maintained. Although this type of treatment shows promise, with such a wide range of methods available and low level of evidence to support each, there is inadequate support for any one method at this time.
The American Academy of Neurology notes in the 2004 Position Statement regarding the use of embryonic stem cells in biomedical research:
While the potential of embryonic stem cell research to result in breakthrough therapies is real, it is important to recognize that the translation of research into therapy will take many years, and it is also possible that such therapies may not ever be realized.
The Movement Disorder Society (Fox, 2011) updated the evidence-based medicine review of treatments for motor symptoms of Parkinson's disease. In the update, there were no new studies to change the conclusion that surgical outcomes of human fetal cell transplantation as a treatment for Parkinson's disease remained investigational and evidence on efficacy was insufficient.
With concerns regarding the use of embryonic tissues at the center of ethical and political debates, it is unlikely that any large-scale use of fetal mesencephalic transplantation will be forthcoming. In response to such concerns, investigations into the use of porcine fetal mesencephalic transplantation are being conducted. While similar methodological issues exist as with human fetal transplantation, fewer ethical concerns make this type of procedure more widely accepted. At this time, only a few small clinical trials have been described in the literature, but with some promising results. Further randomized controlled studies must be conducted before this type of therapy may be adequately evaluated for use and long-term efficacy in the clinical setting.
The transplantation of tissues from the adrenal gland (adrenal-to-brain), fetal mesencephalic allograft and fetal xenografts have been proposed as a replacement source of dopamine-generating neurons to treat individuals with Parkinson's disease. However, data are lacking regarding the long-term safety and effectiveness of these proposed therapies and further randomized controlled studies must be conducted before this type of therapy may be adequately evaluated for use in the clinical setting.
Autograft: The process of taking tissue from one part of the body and transplanting it into another part of the body with the goal of treating some specific disease or condition.
Fetal Allograft: The process of taking tissue or cells from an aborted fetus and transplanting it into the body of a recipient with the goal of treating some specific disease or condition.
Mesencephalic: Pertaining to the mid-section of the brain.
Xenograft: The process of taking tissues from another species, such as pigs, and transplanting it into the body of a human with the goal of treating some specific disease or condition.
- Bhattacharya N, Chetri MK, Mukherjee KL, et al. Can human fetal cortical brain tissue transplant (up to 20 weeks) sustain its metabolic and oxygen requirements in a heterotopic site outside the brain? A study of 12 volunteers with Parkinson's disease. Clin Exp Obstet Gynecol. 2002; 29(4):259-266.
- Drucker-Colin R, Verdugo-Diaz L. Cell transplantation for Parkinson's disease: present status. Cell Mol Neurobiol. 2004; 24(3):301-316.
- Fillmore HL, Holloway KL, Gillies GT. Cell replacement efforts to repair neuronal injury: a potential paradigm for the treatment of Parkinson's disease. NeuroRehabilitation. 2005; 20(3):233-242.
- Fink JS, Schumacher JM, Ellias SL, et al. Porcine xenografts in Parkinson's disease and Huntington's disease patients: Preliminary results. Cell Transplantation. 2000; 9(2):272-278.
- Fox SH, Katzenschlager R, Lim SY, et al. The Movement Disorder Society evidence-based medicine review update: treatments for the motor symptoms of Parkinson's disease. Mov Disord. 2011; 26 Suppl 3:S2-S41.
- Freed CT, Greene PE, Breeze RE, et al. Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med. 2001; 344(10):710-719.
- Jankovic J. An update on the treatment of Parkinson's disease. Mt Sinai J Med. 2006; 73(4):682-689.
- Kopyov OV, Jacques D, Lieberman A, et al. Clinical study of mesencephalic intracerebral transplant for the treatment of Parkinson's disease. Cell Transplant. 1996; 5(2):327-337.
- Kopyov OV, Jacques D, Lieberman A. Outcome of intrastriatial fetal mesencephalic grafts for Parkinson's patients is directly related to the volume of grafted tissue. Exp Neurol. 1997; 146(2):536-545.
- Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders. Nature. 2006; 441(7097):1094-1096.
- Ma Y, Feigen A, Dhawan V, et al. Dyskinesia after fetal cell transplantation for Parkinsonism: a PET study. Ann Neurol. 2002; 52(5):628-634.
- Olanow CW, Gracies JM, Goetz CG, et al. Clinical pattern and risk factors for dyskinesias following fetal nigral transplantation in Parkinson's disease: a double blind video-based analysis. Mov Disord. 2009; 24(3):336-343.
- Schumacher JM, Ellias SL, Palmer EP, et al. Transplantation of embryonic porcine mesencephalic tissue in patients with PD. Neurology. 2000; 54(5):1042-1050.
- Schwarz J, Schwarz SC, Storch A. Developmental perspectives on human midbrain-derived neural stem cells. Neurodegener Dis. 2006; 3(1-2):45-49.
- Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services. Diagnosis and treatment of Parkinson's disease: a systematic review of the literature. Evidence Report/Technology Assessment Number 57. 2003. Available at: http://archive.ahrq.gov/downloads/pub/evidence/pdf/parkinsons/parkinsons.pdf. Accessed on December 14, 2012.
- Blue Cross and Blue Shield Association. Fetal mesencephalic transplantation for the treatment of Parkinson's disease. TEC Assessment, 1995; 10(1).
- Blue Cross and Blue Shield Association. Embryonic mesencephalic transplantation for the treatment of Parkinson's disease. TEC Assessment, 2001; 16(8).
- Hallet M, Litvan I. Evaluation of Surgery for Parkinson's disease: A report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology. Neurology. 1999; 53(9):1910-1921.
- National Institute of Health. National Human Genome Research Institute. Learning about Parkinson's. Updated June 27, 2011. Available at: http://www.genome.gov/page.cfm?pageID=10001217. Accessed on January 3, 2013.
- National Institute of Health. Parkinson's Disease. Updated December 7, 2012. Available at: http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html. Accessed on January 3, 2013.
- National Institute of Neurological Disorders and Stroke (NINDS) Parkinson's Disease Information Page. Updated December 31, 2012. Available at: http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_disease.htm. Accessed on January 3, 2013.
||Unlisted procedure, nervous system (when specifiedas adrenal tissue transplant to brian, fetal mesencephalic transplant or fetal xenograft)
||Adrenal tissue transplant to brain
|ICD-10-CM (effective 10/01/15)
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