Bone marrow transplants led to nerve cell restoration in a mouse model of Friedreich’s ataxia (FA), a study showed.
Benefits included improvements in movement, less nervous system damage, and the formation of new nerve cells.
The study, “Bone marrow transplantation stimulates neural repair in Friedreich’s ataxia mice,” appeared in the journal Annals of Neurology.
FA is an inherited disorder caused by a mutation in the FXN gene coding for frataxin, a protein that is essential for the proper functioning of mitochondria, the cell’s power plants. Frataxin normally binds with iron, allowing certain enzymes to use it for energy production. With frataxin deficiency, energy production is impaired and the unbound iron damages cells.
Patients with FA typically develop neurological disability. Nerve cell atrophy and alterations in glial cells are thought to contribute to the disease.
Glial cells form the myelin cover that protects nerve cells. They also provide support for nerve cells and synapses, spaces between nerve cells that facilitate nervous system signaling.
Despite increasing knowledge of the causes of FA, no treatment is able to promote nerve tissue repair.
Research suggests that stem cells, particularly those in bone marrow, are able to migrate and integrate into the nervous system, where they may help originate nerve cells and glial cells. These properties make bone marrow transplants from a healthy donor an approach with significant therapeutic potential for diseases such as FA, the researchers said.
Granulocyte-colony stimulating factor (G-CSF) and stem cell factor (SCF) are two molecules that stimulate the production and maturation of stem cells. The research team had previously shown that the factors increase the number of bone marrow-derived cells in the brains of both healthy animals and animals with central nervous system injury. This may lead to increased nerve cell repair in FA, they reported.
Using a mouse model of FA, the scientists looked at bone marrow transplants’ ability to repair cells carrying a normal FXN gene. They applied a fluorescent tag to the cells so they could see what happened. They also tested whetherG-CSF and SCF increased cell integration in the nervous system and improved the transplants’ therapeutic effectiveness.
The animals’ movement function was assessed monthly until six months after their transplants, when the mice were euthanized for analysis of their proteins and changes in their nervous systems.
Bone marrow transplants significantly improved the mice’s movement. They also led to the animals having higher levels of frataxin.
In addition, the transplants led to fewer manifestations of nervous system disease. And they helped cells integrate into areas of injury in the brain and spinal cord, where they created mature nerve cells and myelin-producing cells.
G-CSF and SCF increased the number of bone marrow-derived cells in the blood, augmented transplanted cells’ integration into the nervous system, and led to additional improvements in movement.
Mice receiving G-CSF and SCF also had less inflammation in the brain and spinal cord.
Further work is required to determine the mechanisms that G-CSF and SCF use to generate these beneficial effects, the researchers noted.
“Here we provide evidence that transplantation of BM [bone marrow] cells expressing normal copies of [FXN] in a mouse model of FA leads to significant functional, biochemical, and pathological [disease] improvements,” they wrote.
“In conclusion, we have shown that [bone marrow transplantation] offers the prospect of a novel, rapidly translatable, disease-modifying and neuro-regenerative treatment for FA,” they added.