Neurotrophic factor therapy - Prospects and problems
Neurotrophic factor therapy - Prospects and problems
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DOI：
10.1515/cclm.2001.055
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发表时间：
2001-04-01
影响因子：
6.8
通讯作者：
Apfel, SC
中科院分区：
文献类型：
--
作者：
Apfel, SC
在过去的 15 年里，神经营养因子因其治疗多种退行性神经系统疾病的潜力而引起了人们的极大关注，而目前这些疾病还没有治疗方法。这一时期的第一部分的标志是许多新生长因子的发现、表征和克隆，以及在神经疾病动物模型中成功测试这些因子。近年来，生物技术行业和制药行业试图在临床试验中复制动物研究的成功。尽管一些研究显示出中等疗效，但大多数临床试验在证明此类新药的治疗功效方面不太成功。例如，神经生长因子在治疗周围神经病变的两项 II 期临床试验中似乎有效，但在一项大规模 III 期试验中失败了。睫状神经营养因子、脑源性神经营养因子和胰岛素样生长因子-1 均已在治疗肌萎缩性脊髓侧索硬化症的临床试验中进行了测试，其疗效指标充其量也各不相同。尽管如此，仍有许多理由乐观地认为其中一些药物可能在临床上有用。在神经营养因子发挥其潜力之前，许多技术和药理学问题仍有待充分解决。我们与他们的集体经验重新调整了以前的疯狂期望，使它们现在更加现实。这对于该研究领域的成熟是必要且有益的。
Over the past 15 years neurotrophic factors have generated considerable excitement for their potential as therapy for a wide variety of degenerative neurological disorders, for which there is currently no treatment. The first part of this period was marked by the discovery, characterization, and cloning of many new growth factors, and by successful testing of these factors in animal models of neurological disease. In recent years the biotechnology industry and pharmaceutical industry have attempted to replicate the success of the animal studies in clinical trials. Although some studies have demonstrated moderate efficacy, for the most part the clinical trials have been less successful at demonstrating the therapeutic efficacy of this new class of drugs. For example, nerve growth factor appeared to be efficacious in two phase II clinical trials for peripheral neuropathy, but failed in a large scale phase III trial. Ciliary neurotrophic factor, brain derived neurotrophic factor and insulin like growth factor-1 have all been tested in clinical trials for the treatment of amyotrophic lateral sclerosis, with at best, variable indications of efficacy.Nevertheless, there are still many reasons to be optimistic that some of these agents may be useful clinically. Many technical and pharmacological issues remain to be adequately addressed, before neurotrophic factors can live up to their potential. Our collective experience with them has re-adjusted previously wild expectations, so that they are now much more realistic. This is necessary and beneficial for the maturation of this field of study.