Modalis Therapeutics has announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease (RPD) designation to MDL-101.MDL-101 is an experimental epigenetic therapy that targets the LAMA1 gene, which is highly similar to LAMA2. It employs a guide nucleotide to upregulate LAMA1 expression, delivered via an AAV vector specific to muscle tissue. LAMA2-CMD is a severe form of congenital muscular dystrophy caused by the absence of the LAMA2 protein, which consists of over 3,000 amino acids.By compensating for the loss of function caused by LAMA2 mutations, MDL-101 has the potential to provide a long-lasting, one-time treatment for patients with LAMA2-CMD.This experimental therapy is being developed for congenital muscular dystrophy type 1A (LAMA2-CMD).The FDA's RPD designation is granted to treatments for serious, life-threatening conditions that primarily affect children under 18 and fewer than 200,000 people in the U.S.

Modalis Therapeutics宣布，美国食品和药物管理局（FDA）已将罕见儿科疾病（RPD）指定为MDL-101。MDL-101是一种实验性表观遗传疗法，靶向与LAMA2高度相似的LAMA1基因。它使用指导核苷酸来上调LAMA1的表达，该表达通过对肌肉组织特异的AAV载体传递。LAMA2-CMD是一种严重的先天性肌营养不良症，由不存在由3000多个氨基酸组成的LAMA2蛋白引起。通过补偿由LAMA2突变引起的功能丧失，MDL-101有可能为LAMA2-CMD患者提供持久的一次性治疗。这种实验疗法正在针对1A型先天性肌营养不良症（LAMA2-CMD）开发。FDA的RPD指定用于治疗严重的危及生命的疾病，这些疾病主要影响美国18岁以下儿童和不到20万人。

Upon marketing approval, this designation makes Modalis eligible for a priority review voucher, allowing expedited review of another product. The Orphan Drug application for MDL-101 is also under separate review.Due to its size, conventional gene therapy approaches, such as loading onto an AAV vector, have been challenging, and no current treatments target the root cause of the disease.Modalis' CRISPR-GNDM® technology enables precise modulation of gene expression without introducing double-strand DNA breaks.

在获得营销批准后，这种指定使Modalis有资格获得优先审查凭证，从而可以快速审查另一种产品。MDL-101的孤儿药申请也在单独审查中。由于其规模，传统的基因治疗方法，例如加载到AAV载体上，一直具有挑战性，目前还没有针对该疾病根本原因的治疗方法。Modalis的CRISPR-GNDM®技术能够在不引入双链DNA断裂的情况下精确调节基因表达。

MDL-101 is designed to be a first-in-class treatment, compensating for the LAMA2 deficiency by inducing the expression of the sister gene LAMA1 in muscle tissue. This innovative approach aims to offer a breakthrough therapy for patients with LAMA2-CMD. Source: modalistx.com.

。这种创新方法旨在为LAMA2-CMD患者提供突破性治疗。来源：modalistx.com。