MGTA-456 is a stem cell therapy developed by Magenta Therapeutics for the treatment of inherited metabolic disorders such as adrenoleukodystrophy (ALD). MGTA-456 is derived from umbilical cord stem cells and can be administered to a patient via a bone marrow transplant.

The efficacy of MGTA-456 is being investigated in a Phase 2 clinical trial for inherited metabolic disorders after yielding encouraging proof-of-concept data in leukemia patients. MGTA-456 is a U.S. Food and Drug Administration (FDA)-regulated drug, but is yet to receive any special status from the FDA or the European Medicines Agency (EMA).

How MGTA-456 works

MGTA-456 is an allogeneic stem cell therapy. This means that the umbilical cord stem cells are derived from a matching donor and expanded before being transplanted into the patient’s body. This is called a hematopoietic stem cell transplant (HSCT). HSCT affects the patient’s own bone marrow and usually results in decreased white blood cell production, compromising the patient’s immunity. MGTA-456 can be administered in higher doses to compensate for the time it takes for the white blood cells to repopulate the body.

In ALD, there is a mutation in the ABCD1 gene, which leads to the production of non-functional adrenoleukodystrophy protein (ALDP) or no production of the protein at all. ALDP is responsible for the transport of molecules called very long-chain fatty acids (VLCFA) to a compartment inside cells called the peroxisome, where they are broken down. In the absence of functional ALDP, VLCFAs accumulate inside cells and lead to loss of the protein coat, called the myelin sheath, that provides insulation for nerve cells. This results in the neurologic dysfunction seen in ALD patients. VLCFA accumulation can also cause adrenal insufficiency in ALD patients.

MGTA-456, when transplanted via HSCT, helps in the production of cells that can synthesize ALDP via the non-mutated ABCD1 gene, thereby preventing the breakdown of myelin (demyelination). MGTA-456 can also help replenish an area in the brain called the microglial compartment, implicated in many inherited metabolic disorders.

MGTA-456 in clinical trials

Pre-clinical studies in mouse models have shown replenishment of the microglial compartment in the brains of animals when umbilical cord stem cells were transplanted via HSCT.

Proof-of-concept data from an open-label interventional Phase 2 clinical trial (NCT03674411) first demonstrated the efficacy of MGTA-456 in leukemia patients.

Now, a single-arm, open-label Phase 2 clinical trial (NCT03406962) is underway to evaluate the efficacy of MGTA-456 in inherited metabolic disorders such as Hurler syndrome, metachromatic leukodystrophy (MLD)globoid cell leukodystrophy (GLD), also known as Krabbe disease, and childhood cerebral ALD (CALD). Preliminary results presented at the American Society of Hematology (ASH) meeting in 2018 showed positive data from four patients, two with Hurler syndrome and one with CALD. These patients also showed good tolerance to high doses of MGTA-456, with the only reported adverse events being nausea and vomiting.

However, there was a safety concern in the administration of MGTA-456 in Hurler syndrome patients, as they were seen to develop autoimmune cytopenia, which resulted in one death. Magenta Therapeutics said the fatality was not related to MGTA-456, citing consultations with experts.

The trial is still recruiting participants at the University of Minnesota.

Other information

Magenta Therapeutics is investigating the potential benefits of MGTA-456 in other diseases. A Phase 2 clinical trial to evaluate the effects of the treatment in sickle cell anemia is expected to start this year.


Adrenoleukodystrophy News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.