基因治疗使一个致命的儿童疾病的进展

研究人员已经迈出了重要一步，在开发基因治疗对一个致命的神经退行性疾病，打击儿童。通过提供一个工作版本的基因产生的一个关键酶，缺乏Batten病，科学家迟发症状和延长寿命与病犬。

今天网上出现的文件科学转化医学。

单基因治疗提高生活质量

“One treatment of gene therapy gave these dogs a remarkable improvement in their quality of life,” said Beverly L。 Davidson, PhD, director of the Raymond G。 Perelman Center for Cellular and Molecular Therapeutics at The Children’s Hospital of Philadelphia。 “If the outcome is equally profound in children with the same enzyme deficiency, this would represent a great benefit for affected children and their families。”

Davidson’s team focused on the rare, inherited childhood disorder, late infantile neuronal ceroid lipofuscinosis, also called Batten disease。 Batten disease is one of a group of inherited diseases called lysosomal storage disorders, which impair the body’s ability to dispose of cellular waste products。 Having a naturally occurring disease that mimics Batten disease, the dogs used in this study provide a biological model for researching human disease。

基因突变在Batten病的影响

在大多数与Batten病的晚期婴儿型和受影响的狗的孩子，突变的TPP1 gene disable the body’s ability to produce the enzyme tripeptidyl peptidase 1 (TPP1), which normally allows brain cells to recycle cellular waste。 The abnormal waste buildup erodes toddlers’ abilities to walk, talk, think, and see。 Symptoms and seizures usually appear between ages 2 and 4, and the disease progresses, with most children dying by age 10。

处理交货

In lysosomal storage diseases that affect other organs such as liver or muscle, doctors treat patients with repeated infusions of the missing enzyme into blood vessels, but infusion into vessels will not work when brain tissue is involved, as in Batten disease。 Instead, direct infusions into the brain would be required。 Indeed, there currently is an experimental therapy testing whether twice-monthly infusions of enzyme into the brains of TPP1-deficient children impacts the disease course。

In this study, Davidson and colleagues used a non-disease-causing adeno-associated virus to deliver the corrective gene into specialized cells in the dogs’ brains。 The researchers delivered the virus once at 3 months of age。 The specialized cells secreted the enzyme (TPP1) encoded by the gene into the cerebrospinal fluid around the brain for the months that followed the one-time treatment。

The enzyme spread throughout the dogs’ brains, and the researchers measured evidence of its expression in cerebrospinal fluid for months。 The dogs showed striking clinical improvements。 Compared to untreated control dogs affected by the disease, the treated dogs walked with a more normal gait, navigated a maze, and better interacted with other dogs。 Although the dogs were not cured, their disease progression and cognitive decline were slowed, and they had longer lifespans。

If this gene therapy approach can achieve comparable results in children, said Davidson, it would greatly improve their quality of life。 In addition to improvements in motor control and cognition, it could reduce patient risk by avoiding repeated access to the brain for life-long enzyme infusions or the need for implanted enzyme-delivery devices。

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