Dr. Avencia Sanchez-Mejías’ ex-vivo therapeutic approach to LAMA2-CMD
Dr. Avencia Sanchez-Mejías has been investigating how haematopoietic stem cells from LAMA2-CMD patients’ bone marrow, can be genetically corrected to potentially improve quality of life.
Dr. Avencia Sanchez-Mejías and her research team at the University of Pompeu Fabra in Barcelona have carried out a number of investigations focused on an ex-vivo therapeutic approach to LAMA2-CMD. An ex-vivo approach consists of isolating certain cells from a patient, then genetically correcting these cells in the lab, before returning them to the patient so that they can function normally in the body and exert therapeutic effects.
To test this approach, the team based in Barcelona have carried out several studies on mice that carry a mutation in the LAMA2 gene. These mice are commonly used as a scientific animal model to study LAMA2-CMD. Previous research has shown that cells called haematopoietic stem cells, that come from the bone marrow, can release products which circulate in the bloodstream, and can enter the muscle where it is inflamed and damaged, leading to therapeutic effects. To confirm this, the research team transplanted bone marrow from healthy mice, into LAMA2-CMD mice, and this indeed led to an increase in life expectancy for the LAMA2-CMD mice.
Increased muscle strength
In another experiment, the researchers isolated bone marrow cells from LAMA2-CMD mice, and genetically corrected the LAMA2 mutation in these cells in the lab. These corrected bone marrow cells were then injected back into the same LAMA2-CMD mice, where their derived products circulated through the blood and entered the damaged muscle. This treatment resulted in improved life expectancy as well as increased muscle strength in the LAMA2-CMD mice.
These experiments provide promising data supporting that the ex-vivo approach could lead to therapeutic improvements for LAMA2-CMD patients. Importantly, they also highlight the potential to genetically correct other types of cells, such as hematopoietic stem cells, and not only muscle stem cells. An effective therapy for LAMA2-CMD will likely combine these different strategies to maximise therapeutic results.