The design of clinical trials for cell transplantation into the central nervous system

Protection and repair of the injured spinal cord: a review of completed, ongoing, and planned clinical trials for acute spinal cord injury

“…For example, analysis of the large Sygen database has been valuable for defining the variance in spontaneous neurological recovery among patients deemed to have the same injury severity. 43 Subsequently, a number of authors have published recommendations for the scientific and ethical conduct of future trials, including Tator 139 (select recommendations are provided in Table 2), Cesaro, 24 and Sagen 127 with the latter 2 addressing cell replacement therapies. A parallel effort has come from the International Campaign for Cures of Spinal Cord Injury Paralysis, which published 4 documents in 2007 43,89,135,143 designed to improve SCI clinical trials (a summary of these recommendations is provided in Table 2).…”

Cellular therapy for childhood neurodegenerative disease. Part II: clinical trial design and implementation

“…In certain clinical circumstances, such as a recent traumatic injury, or an inflammatory or autoimmune process causing damage to the blood-brain barrier, there is at least the theoretical possibility of delivering effective cellular therapy to the CNS via peripheral intravenous injection. 8,20 In general, the timing of such therapy relative to the time of injury occurrence may offer only a narrow window of efficacy. Finally, recent work in animal models suggests that the surgical delivery of cells within semipermeable capsules may allow transplants with limited or no immunosuppresion, transplantation of xenografts, or other novel strategies.…”

“…Second, many investigators and institutional review boards consider it most ethical to enroll patients in innovative Phase I trials who may, due to advanced disease and lack of viable options, have a more acceptable risk/ benefit profile than patients early in the disease course. 8,10,16 However, multiple factors argue against enrollment of patients in the late stages of disease, particularly in the case of neurodegenerative and other neurological disorders that result in significant end-stage debility. First, patients in the late stages of disease are susceptible to anesthetic, medical, and surgical complications due to disease comorbidities, including pneumonia and other infections, aspiration, metabolic or drug side effects, exacerbation of disease-associated seizure disorders, and others.…”

“…In the case of focal episodic disorders such as CNS injuries from trauma or stroke, time between injury and enrollment, the exact injury location (for example cortical versus basal ganglia stroke), and injury mechanism (for example, ischemic versus hemorrhagic stroke) should be comparable. 8,13,17 Ideally, patients should also suffer from similar comorbidities and have the same general health status. Although homogeneous populations are scientifically ideal for studying efficacy, they may fail to identify susceptibility to adverse effects or alternatively to detect benefit in particular patient subpopulations not represented in the initial studies.…”

Pharmaceutical, cellular and genetic therapies for Huntington's disease

“…The clinically beneficial effect of transplantation with primary cells in HD is dependent on two main issues: firstly, whether the neural graft will survive and replace lost neurons in the place(s) where required, and secondly, whether the neural graft can integrate into the host neuronal circuitry and contribute to normal physiological processing within the host brain [58]. This approach can only be offered as a therapeutic tool for patients with HD once the safety and efficacy of the procedure has been confirmed in both animal models of HD and clinical trials of patients with HD [59].…”