Dr. Avencia Sanchez-Mejías’ ex-vivo therapeutic approach to MDC1A

Dr. Avencia Sanchez-Mejías has been investigating how haematopoietic stem cells from MDC1A 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 MDC1A. 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 MDC1A. 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 MDC1A mice, and this indeed led to an increase in life expectancy for the MDC1A mice.

Increased muscle strength

In another experiment, the researchers isolated bone marrow cells from MDC1A 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 MDC1A 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 MDC1A mice.

These experiments provide promising data supporting that the ex-vivo approach could lead to therapeutic improvements for MDC1A 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 MDC1A will likely combine these different strategies to maximise therapeutic results.