AANS Neurosurgeon | Volume 28, Number 1, 2019

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Stem Cells in Neurosurgery: Panacea on the Horizon?

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Medical news, like all news, blatantly works to grab our attention with hyperbolic claims about miracle interventions. Countless newsletters and updates (once a blessing, now a curse from which it is impossible to unsubscribe) extol new therapies, including the most impressive of them all – stem cell therapy.   

Most recently, the early results using a stem cell line known as S623 showed some remarkable recovery in patients with chronic deficits after stroke. As neurosurgeons, these are not patients we routinely treat, but it is easy to understand the audible gasps muttered when many of the lay public watched videos of patients again able to use the limbs that were paralyzed.  

The promise of stem cells has been hard to deliver. For instance, stem cells have never been shown to convey any clinical benefit in patients with several forms of heart disease. The ALLSTAR trial, for example, was halted in 2017 after a pre-specified administrative interim analysis was performed on six-month follow-up data. If the S623 stroke trial is corroborated and a lasting effect demonstrated, then the brain may prove the exception to other organs in responding to the promise of stem cell treatments.

Not surprisingly, the allure of stem cell research has led more than one researcher into treacherous waters. In the stroke trial, there is some anecdotal evidence that the reasoning and objectivity of the medical researchers, biotechnology executives and investors was flawed. As neurosurgery strives for the highest quality of evidence, it is concerning that apprehensions were voiced in the stroke-stem cell trial about missing the major prespecified endpoint and alternatively reporting secondary findings, which must be considered exploratory at best.

Other scandals have plagued the field as well. Hundreds of millions of dollars have been spent on cardiac stem cell research over nearly two decades without any sign of tangible success or progress. A prominent teaching hospital in Boston, as reported by Retraction Watch, as part of a long-running scandal, agreed to give back $10 million to the U.S. government in response to fraud charges against three prominent stem cell researchers.

Due to the very expensive nature of creating a viable stem cell therapy and running the necessary clinical trials, strategic business decisions also can override science. The RECOVER stroke trial was halted a few years back due to slow enrollment, which raises questions about the planning of the trials from the beginning. The same fate apparently happened to another stroke trial, but we know less about the reasoning as it appears the entire company around this product was terminated.

Most would agree that acute neurological conditions, such as stroke and traumatic brain injury, are highly attractive targets for cell therapy. However, most efforts do not progress as planned and there are several common threads that are worth pointing out:

  • Slow enrollment due to natural variation of the patient presentation and clinical picture between screening and completion.
  • Trial design remains a challenge.
  • Long lists of exclusion criteria and inability to control for fluctuation of the natural progression of the disease in acute neurological conditions remain a significant barrier to successful enrollment.
  • Uncertainty of funding.

Slow enrollment could also be seen as a critique on the current ideal patient model that is expected to benefit from stem cell therapy – it appears that the majority of patients would not be selected for such a therapy and that a narrow group of patients would benefit. While neurosurgical centers have gained significant experience with making on-the-fly decisions about enrollment and screening of patients who participate in interventional stroke trials for ischemic stroke and intracerebral hemorrhage, it requires strong hands-on involvement of investigators. 

Linked to the inability to predict the speed of enrollment is the uncertainty of the funding model for the entire trial, since highly experienced and sometimes costly components of the institutional research infrastructure have to be maintained throughout the duration of the trial. Once a trial has started, we naturally do not want it to wither away in the middle due to financial problems. This is directly influenced by the overall assessment of the business model for autologous cell therapy in acute neurological conditions. Factors are complicated at best, including the emergence of the neurological condition, fluctuation of patient condition, high liability in decision making and the requirement of a big multidisciplinary team effort, making it not very attractive for investors overall.

Will our future as neurosurgeons be filled with patients who require ultra-specialized implantation of stem cells to treat neurological problems, ranging from Parkinson’s to multiple sclerosis, stroke to traumatic brain injury? If the promising results of the SB623-Stroke trial cause the pendulum to swing back and show its incredible importance and potential, then perhaps. This could serve as a template for other neurosurgeons to design successful therapies.

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