Modalis Therapeutics Corporation announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to MDL-101, a novel precision medicine being developed for the treatment of congenital muscular dystrophy type 1a (LAMA2-CMD). This designation aims to accelerate the development of treatments for rare diseases affecting fewer than 200,000 people in the United States.
Addressing Unmet Needs in LAMA2-CMD
LAMA2-CMD is a severe, early-onset congenital muscular dystrophy caused by the absence of the LAMA2 protein. This deficiency leads to muscle weakness and reduced survival, and currently, there are no approved treatments that address the underlying cause of the disease. The size of the LAMA2 protein, composed of over 3,000 amino acids, has posed challenges for traditional gene therapy approaches.
Haru Morita, CEO and President of Modalis, stated, "LAMA2-CMD is a serious, life-threatening rare disease that causes muscle weakness and reduced survival in patients. Currently, there is no approved treatment for LAMA2-CMD in the United States. We are hopeful that MDL-101, which has the potential to activate LAMA1, the sister gene of LAMA2, the causative gene of this disease, and achieve a fundamental cure, will become the first treatment that improves the prognosis of these patients."
Novel CRISPR-GNDM Approach
MDL-101 utilizes Modalis’ proprietary CRISPR-GNDM technology, which allows for precise modulation of gene expression without altering the patient's DNA sequence. The therapy aims to induce expression of the LAMA1 gene, a sister gene of LAMA2, in muscle tissues, thereby compensating for the deficient function of LAMA2. This approach represents a potential first-in-class therapeutic for LAMA2-CMD.
About MDL-101
MDL-101 is an experimental, epigenetic editing therapy designed for LAMA2-CMD treatment. It consists of a guide nucleotide targeting the LAMA1 gene, an enzyme-null Cas9 (dCas9) fused with a trans-activating domain driven by a muscle-specific promoter, and is coded in a muscle-specific AAV vector. By upregulating LAMA1 gene products in patients’ muscle tissue, MDL-101 aims to provide a durable, one-time treatment to benefit individuals living with LAMA2-CMD.
