rhLAM-111 (recombinant human laminin-111) is an experimental gene therapy currently being explored in pre-clinical studies by laboratories in the United States, Canada, and the European Union to potentially treat Duchenne muscular dystrophy (DMD) and congenital muscular dystrophy type 1A (MDC1A).
How rhLAM-111 works
rhLAM-111 acts in several ways to treat muscular dystrophy.
In MDC1A, rhLAM-111 can replace laminin, a structural protein that is normally present in embryonic muscle tissue, but absent in adult muscles and in the disease. Researchers are hopeful that, if supplied early enough, rhLAM-111 could eliminate the symptoms of muscular dystrophy.
rhLAM-111 can also increase the production of alpha-7 beta-1 integrin and utrophin. Alpha-7 beta-1 integrin is another structural protein; utrophin is a protein similar to dystrophin, the protein missing in DMD, which is normally expressed during embryonic development and then turned off. It is hoped that the combination of increased production of both alpha-7 beta-1 integrin and utrophin may be able to prevent the progression of muscle wasting in DMD.
Finally, rhLAM-111 is thought to stimulate muscle healing pathways. Within muscle tissue, even in adulthood, there is a type of resident stem cell called a satellite cell. These cells can divide and differentiate in new replacement muscle cells, replacing damaged cells and healing injuries. rhLAM-111 can stimulate satellite cells to divide and differentiate, which could promote muscle healing in muscular dystrophy.
Research has demonstrated that the introduction of rhLAM-111 can replace the laminin that is absent in MDC1A, reducing symptoms of the disease and increasing life expectancy in a mouse model of MDC1A.
In addition, increasing the production of rhLAM-111 in adult muscle cells grown in a laboratory led to an increase in the production of alpha-7 beta-1 integrin, which seemed to counteract the absence of dystrophin by providing structural support to muscle cells.
Researchers are in the process of developing a gene therapy that increases the production of rhLAM-111 in muscle tissues. The treatment will contain a modified virus that cannot cause disease and that carries the gene encoding for rhLAM-111. It is hoped that cells infected with the virus will begin producing rhLAM-111, which in turn will increase the production of alpha-7 beta-1 integrin and utrophin and stimulate the repair of muscle damage.
Phase 1 clinical trials testing this approach are expected to begin in mid-2021.
Last updated: 07/15/2019
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