英國劍橋大學神經科學所日前發表研究結果，發現間葉幹細胞具有神經保護性，能改善次發惡性型多發性硬化症(secondary progressive multiple sclerosis)。此成果已刊登在一月的線上刺胳針神經學(Lancet Neurology)期刊。

此研究為10位患有次發惡性型多發性硬化症，確認病患視神經有去髓鞘現象，經自體骨髓間葉幹細胞移植，於6-10個月後，發現視力(Visual Acuity)、視覺誘發反應(Visual-Evoked Response latency)和視神經範圍(Optic Nerve Area)有顯著地改善，並且移植後無任何嚴重副作用產生。

另外，病患在多發性硬化症擴展殘疾狀況評分表(Expanded Disability Status Scale； EDSS)的評估結果有殘疾減少的現象。

但針對彩色視覺(Color vision)、視野(Viscual field)、黃斑部體積(Macular volume)、視神經纖維厚度(Retinal nerve fiber layer thickness)與受損腦部磁化轉化比率(magnetization transfer ratio)等無明顯改善，故科學家希望未來能找出更有效的方式，結合幹細胞一起治療。

January 31, 2012 — Results of a small proof-of-concept study hint that autologous mesenchymal stem cells may have neuroprotective effects in multiple sclerosis (MS).

The study involved 10 patients with secondary progressive MS and objective evidence of optic nerve involvement resulting from demyelination. Over the course of 6 to 10 months after a single infusion of autologous mesenchymal stem cells in the central nervous system (CNS), researchers saw evidence of functional, neurophysiological, and structural improvement in vision without evidence of significant adverse effects.

The patients also experienced a reduction in functional disability, as measured by the Expanded Disability Status Score (EDSS).

Peter Connick, MRCP, from the Department of Neurosciences, University of Cambridge, United Kingdom, and colleagues reported the results in an article published online January 10 in Lancet Neurology.

"The signs of repair measured in most of the patients...raise substantial interest," Mark S. Freedman, MD, from the University of Ottawa Neurology Program in Ontario, Canada, and Antonio Uccelli, MD, from the Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Italy, write in a linked comment.

Major Unmet Clinical Need

Despite major advances in immunomodulatory therapies for patients with relapsing-remitting MS, there are no proven or available treatments to slow, stop, or reverse the accumulation of fixed disability characteristic of secondary progressive MS, the study team notes. The absence of treatments for this type of MS, which affects more than half of the patient population is a "major unmet clinical need," they write.

Their study grew out of preliminary evidence suggesting that mesenchymal stem cells have a beneficial effect in acute and chronic animal models of MS.

The investigators isolated, expanded, and characterized autologous bone marrow–derived mesenchymal stem cells from 10 patients with secondary progressive MS who had clear and objective evidence of optic nerve involvement, and then readministered them. None of the patients had received interferon-beta or glatiramer acetate within 6 months of entering the trial, or had previously used other disease-modifying therapies at any point.

The primary objective was to assess feasibility and safety. The investigators report that 1 patient developed a transient rash shortly after treatment, and 2 had self-limiting bacterial infections 3 to 4 weeks after treatment, but there were no serious adverse events.

As a secondary objective, they assessed the effect of treatment on the anterior visual pathway "as a model of wider disease," they explain.

After treatment, there was evidence of significant improvement in visual acuity and visual-evoked response latency, and an increase in optic nerve area.

Table. Noteworthy Visual Efficacy Outcomes

Visual Measure	Rate of Change (95% Confidence Interval)	P
Acuity (logMAR units)	−0.2 (−0.03 to −0.01)	.003
Evoked response latency (ms)	−1.33 (−2.44 to −0.21)	.020
Optic nerve area (mm2)	0.13 (0.04 - 0.22)	.006

MAR = minimum angle of resolution

In their comment, Dr. Freedman and Dr. Uccelli say the improvement seen in the anterior visual pathway "might be an indicator of a more general process within the CNS," which is suggested by the reduction in functional disability on the EDSS. The "large, but statistically non-significant, changes in T1 lesion volume and magnetisation transfer ratio" also support this possibility, they note.

However, many visual measures did not show statistically significant changes after treatment, including color vision, visual fields, macular volume, retinal nerve fiber layer thickness, or optic nerve magnetization transfer ratio. "Particularly disappointing," Dr. Freedman and Dr. Uccelli say, were the results for optical coherence tomography, "which we all hoped might be a sensitive index for repair."