Despite hope to the contrary, it may be premature to sing the praises of healthy cell transplantation as a treatment option for neurodegenerative diseases. Earlier this week, the Michael J. Fox Family Foundation interviewed Huntington’s disease researchers about their recently published study on the effects of embryonic neural tissue grafts in Huntington’s-affected brains. A transcript of the interview can be found here. Their study reveals that the promise of fetal neural graft therapy faces unexpected challenges.
In the 1990’s, scientists touted cell transplantation as a therapy option for neurodegenerative diseases. Researchers thought that replacing dying neurons with fresh, unaffected ones would revive neural function and slow, or even stop, disease progression. However, recent findings reported in PNAS and Nature suggest that Huntington’s disease can co-opt implanted healthy neural cells and tissues, leading them to degenerate at the same rate as (or even faster than) the patient’s own disease-mutation-containing tissue.
In the reported study, transplanted neural tissue appeared to follow disease-specific degeneration, even though it did not contain the Huntington’s mutation and was initially unaffected. This means that even without the Huntingtin protein mutation, tissue was susceptible to the same degenerative processes of the disease. In their study, the Huntington’s researchers suggest that diseased tissue may promote a toxic environment that makes it impossible for the healthy tissue to thrive. The kamikaze nature of the diseased neighboring tissue seems to make it challenging for the healthy tissue to survive long term. This finding indicates that using healthy tissue transplantation as a therapy option may be more complicated than originally anticipated.
This is somewhat disheartening news, especially given the media-fueled anticipation of tissue transplantation treatment options. The findings suggest researchers should exercise caution moving forward with basic fetal tissue transplantation therapy. However, there are still variables of transplantation that remain untested (particularly those of environment) and optimism remains that stem cell therapies may have more success in refreshing crucial neural populations.
There are numerous differences between cell-transplantation based therapies and tissue transplantation-based treatments. While the tissue transplants are three-dimensional, differentiated, and further along in development, stem cells are typically delivered in solution, undifferentiated, and at an earlier developmental stage. These differences yield hope that implanted stem cells may not be as susceptible to the degenerative processes presumably provoked by the existing tissue.
Stem cells, being less differentiated, may retain some proliferative capabilities that the fetal transplants do not (they may last longer because they are a potentially renewable source), or they may be less sensitive to the toxic environment created by the diseased neurons. Stem cells may also prove to be less antigenic than tissue transplants, thereby arousing less of a destructive response from the patient’s own immune system. This is particularly true of stem cells derived from the patient (using iPS cells or other sources) as opposed to fetal tissues. Researchers are optimistic that stem cells, which can be induced to develop into neurons, may be able to survive long enough in the diseased neural environment to be able to limit, or even correct, the damage inflicted by the disease.
Hope remains that healthy neural cells and tissue can override disease-imposed degeneration in the affected brain environment. However, these recent findings in Huntington’s patients (which were also observed, to a lesser extent, in Parkinson’s patients), indicate that the seeming silver bullet of neural transplantation may not be quite as simple a solution as was anticipated.
Nevertheless, we at Prize4Life take this news in stride; it serves as another step forward on the road to true ALS treatment development. The more researchers know about the pathology of neurodegenerative diseases, the better they are positioned to direct their experiments to successful treatment options. And the better informed that patients are about potential therapy options, the more educated and healthy decisions they can make about their own treatment. We continue to support research into slowing and stopping neural degeneration in the hope that diseases like Huntington’s, Parkinson’s, and ALS will be cured, and look forward to further advances the field of therapy options.