The Lancet Neurol：阿尔茨海默病疫苗临床试验获得成功

研究者研究发现，治疗阿尔茨海默病活性疫苗可发挥积极效应。

(Credit: © Tyler Olson / Fotolia)

阿尔茨海默病是一种复杂的神经痴呆性疾病，使很多人饱受痛苦并且给社会也带来了巨大的压力。近日，来自瑞典卡罗林斯卡医学院的研究者通过研究，报道了治疗阿尔茨海默病活性疫苗的积极效应。这种新型疫苗CAD106，可以为治疗这种严重的痴呆型疾病提供新的线索。相关研究成果刊登在了国际杂志The Lancet Neurology上。

研究者的这项新的研究疗法涉及到了主动免疫接种，研究者使用一种设计好的疫苗来激发机体对β-淀粉样蛋白质的免疫防御。在对人体的二期临床试验中，这种疫苗经过修饰后可以明显影响有害的β-淀粉样蛋白质。研究者通过研究发现，在80%的病人机体中都可以产生保护性的抗体以对抗β-淀粉样蛋白质，而没有任何副作用。研究者认为疫苗CAD106对并人类说是一种缓和性可容忍的疗法，可以治疗轻中度的阿尔兹海默症，但是现在必须进行大量的试验来确定这种疫苗的有效性。

这项研究由瑞典卡罗林斯卡医学院阿尔茨海默病研究中心的研究者Bengt教授和诺华制药等单位合作完成。（生物谷Bioon.com）

编译自：Alzheimer’s Vaccine Trial a Success

编译者：天使托

doi:10.1016/S1474-4422(12)70140-0
PMC:
PMID:

Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo-controlled, first-in-human study

Prof Bengt Winblad, MDa, , , Niels Andreasen, MDa, Prof Lennart Minthon, MDb, Annette Floesser, MScc, Georges Imbert, PhDc, Thomas Dumortier, MScd, R Paul Maguire, PhDc, Kaj Blennow, MDe, Joens Lundmark, MDf, Matthias Staufenbiel, PhDc, Prof Jean-Marc Orgogozo, MDg, Ana Graf, MDd

Background Immunotherapy targeting the amyloid β (Aβ) peptide is a potential strategy to slow the progression of Alzheimer's disease. We aimed to assess the safety and tolerability of CAD106, a novel active Aβ immunotherapy for patients with Alzheimer's disease, designed to induce N-terminal Aβ-specific antibodies without an Aβ-specific T-cell response.

Methods We did a phase 1, double-blind, placebo-controlled, 52-week study in two centres in Sweden. Participants, aged 50–80 years, with mild-to-moderate Alzheimer's disease were entered into one of two cohorts according to time of study entry and then randomly allocated (by use of a computer-generated randomisation sequence) to receive either CAD106 or placebo (4:1; cohort one received CAD106 50 μg or placebo, cohort two received CAD106 150 μg or placebo). Each patient received three subcutaneous injections. All patients, caregivers, and investigators were masked to treatment allocation throughout the study. Primary objectives were to assess the safety and tolerability of CAD106 and to identify the Aβ-specific antibody response. Safety assessment was done by recording of all adverse events, assessment of MRI scans, physical and neurological examinations, vital signs, electrocardiography, electroencephalography, and laboratory analysis of blood and CSF. Patients with Aβ-IgG serum titres higher than 16 units at least once during the study were classified as responders. This study is registered with ClinicalTrials.gov, number NCT00411580.

Findings Between August, 2005, and March, 2007, we randomly allocated 31 patients into cohort one (24 patients to CAD106 treatment and seven to placebo) and 27 patients into cohort two (22 patients to CAD106 treatment and five to placebo). 56 of 58 patients reported adverse events. In cohort one, nasopharyngitis was the most commonly reported adverse event (10 of 24 CAD106-treated patients). In cohort two, injection site erythema was the most commonly reported adverse event (14 of 22 CAD106-treated patients). Overall, nine patients reported serious adverse events—none was thought to be related to the study drug. We recorded no clinical or subclinical cases of meningoencephalitis. 16 of 24 (67%) CAD106-treated patients in cohort one and 18 of 22 (82%) in cohort two developed Aβ antibody response meeting pre-specified responder threshold. One of 12 placebo-treated patients (8%) had Aβ-IgG concentrations that qualified them as a responder.

Interpretation Our findings suggest that CAD106 has a favourable safety profile and acceptable antibody response in patients with Alzheimer's disease. Larger trials with additional dose investigations are needed to confirm the safety and establish the efficacy of CAD106.

Funding Novartis Pharma AG.