Cell Therapy Instigates Neural Repair In Friedreich’s Ataxia Mice


A research group from Bristol (U.K) have established a potential cell therapy for Friedreich’s ataxia (FRDA) which managed to aid motor coordination, stimulate neural repair and even start to reverse disease pathology in a FRDA mouse model. The group transplanted healthy mouse bone marrow cells into the genetically altered FRDA mice to elicit the reparative effects.

FRDA is a neurodegenerative disease characterised by reduced levels of frataxin protein, and mitochondrial dysfunction. This manifests in progressive impairment of movement and other functions as the disease advances in severity.

The mice used in the disease model were genetically altered to express lower levels of frataxin protein and similar symptoms to those observed in the human FRDA condition, including altered tissue pathology and FRDA like movement disorders.

Bone Marrow Delivery

The group found that transplantation of bone marrow cells that express frataxin into the FRDA mice caused the upregulation of frataxin as well as a number of antioxidative proteins, as well as improving movement and coordination in the mice.

The researchers also observed the reversal of FRDA disease pathology, along with integration of transplanted bone marrow cells into damaged nervous system tissue and transplanted cells contributing genetic material to neurons and myelinating Schwann cells.

To improve both the delivery and efficacy of transplanted bone marrow cells to the nervous system, the researchers treated a sub-group of mice with granulocyte colony stimulating factor and stem cell factor proteins.

They found that the addition of these proteins increased the levels of transplanted bone marrow cells in circulation, as well as improving motor coordination and general activity of the mice. These proteins have been shown previously to have a disease modifying effect on FRDA mice – by the same Bristol based group – without the use of bone marrow cells, and are treatments that are already registered for use in other conditions.

Current Treatments Limited

At present, treatments for FRDA are limited to non-existent, with no currently licensed therapeutics that effect disease progression. Instead, therapies centre on managing the disease symptoms, and with the disease ultimately affecting the nervous system, heart and musculoskeletal system there are multiple counselling and physical therapies recommended to patients.

Drugs prescribed for FRDA are primarily for the many comorbidities that arise from the disease, with cardiovascular issues, diabetes and eye conditions being common issues among people with FRDA.

Most strategies have focussed on antioxidative treatments due to the increased oxidative stress from reduced mitochondrial function, or have tried to increase the expression of frataxin. Another promising area of research is from cell and gene therapies, where healthy cells, or cells which have been gene edited, can be transplanted into someone with FRDA to elicit a therapeutic effect.

To truly combat the disease a therapeutic strategy which stops, or reverses, the ongoing neurodegeneration in FRDA is a necessity. This has led to the research from Bristol (U.K), where the cell therapy exhibited in this research may be a life changing option for people with FRDA.

Next Steps

Cell and gene therapies may be the key to solving the treatment issues of FRDA as the genetic cause of the disease is reasonably well characterised, meaning the introduction of cells or genes to specifically combat the FRDA gene sequence is much simpler than in diseases where there can be multiple different genes that contribute to the disease; late-onset Alzheimer’s disease being one of these conditions.

The use of bone marrow transplantation alongside the protein factor treatments may offer a rapidly translatable and disease modifying treatment for people with FRDA. Although these results are extremely promising they are only in an animal model.

Use of this therapy in a clinical trial will hopefully lead to the replication of these results in humans, and the subsequent implementation of this treatment to people with FRDA.

Kemp KC, Hares K, Redondo J, Cook AJ, Haynes HR, Burton BR, Pook MA, Rice CM, Scolding NJ, Wilkins A.
Bone marrow transplantation stimulates neural repair in Friedreich’s ataxia mice.
Annals of Neurology. 2018 Mar 13. doi: 10.1002/ana.25207

Last Updated on November 10, 2022