Researchers to Assess Gene Editing Technology for Friedreich Ataxia Following MDA, FARA Collaboration


The research grant aims to diversify Friedreich ataxia treatments, addressing challenges in trial design and therapeutic strategies for this condition.

Jonathan Watts, PhD, a professor of RNA therapeutics at UMass Chan Medical School

Jonathan Watts, PhD

According to an announcement from the Muscular Dystrophy Association (MDA) and the Friedreich’s Ataxia Research Alliance (FARA), the 2 organizations have committed a $300,000 research grant to study novel genetic technologies to treat Friedreich ataxia (FA), a rare neuromuscular disorder. The grant, awarded to several notable research physicians, involves prime editing (PE), a next-generation CRISPR gene editing tool that aims to remove the GAA expansions in the frataxin (FXN), or the underlying root cause of FA.1

Otherwise known as the Paired Prime Editors to Treat Friedreich’s Ataxia grant, this money will be used to evaluate several PE approaches, including a split prime editing system, in which 2 halves of the PE machinery are delivered as separate molecules. This approach allows researchers the ability to quickly test combinations of editing enzymes with desirable properties. The hope is that the grant will support a diverse number of research opportunities to thereby increase the odds that 1 method will be found successful.

"Our team of investigators is excited to bring multi-disciplinary expertise to the unique challenges of developing PE for FA. With an aim to demonstrate robust and specific GAA repeat removal from the FXN gene in human FA cells, this new and promising technology will require optimization on several fronts," Jonathan Watts, PhD, a professor of RNA therapeutics at UMass Chan Medical School and one of the recipients of the grant, said in a statement.1 "I’m grateful the Muscular Dystrophy Association and Friedreich’s Ataxia Research Alliance have come together to support this research."

FA is caused by a defect in a gene labeled FXN, which carries the genetic code for the production of a protein called frataxin. Frataxin is necessary for the proper function of the energy-producing part of a cell. In FA, an abnormal pattern in the DNA sequence of the protein appears hundreds or more times, which disrupts the normal production of frataxin. Research has shown that a without a normal level of frataxin, certain cells in the body, including the peripheral nerve, spinal cord, brain, and heart muscle cells, produce energy less effectively and may have a buildup of toxic byproducts that lead to oxidative stress.2

READ MORE: Prospective Cohort Study Identifies Critical Predictors of Survival in Friedreich Ataxia

Gene editing becomes an attractive idea for FA because once GAA repeats are removed, the edited FXN gene will still be under control of its natural regulator, thus alleviating concerns about the overexpression of frataxin. As of now, there is 1 recently FDA-approved therapy for FA, omaveloxolone (Skyclarys; Biogen); however, there are no approved treatments that target the root etiology: low levels of frataxin. Omaveloxolone, an orally active, Nrf2 activator and NF-kB suppressor, targets dysfunctional inflammatory, metabolic, and bioenergetic pathways.

Sharon Hesterlee, PhD, chief research officer at the MDA

Sharon Hesterlee, PhD

"We’re proud to co-fund this research with FARA. There has been a longstanding collaboration between our organizations for the benefit of the families we serve, including previous work together with FARA’s clinical research network," Sharon Hesterlee, PhD, chief research officer at the MDA, said in a statement. "This research grant increases the likelihood of a breakthrough gene therapy for those who are living with Friedreich's ataxia. Early research in this area has shown significant promise, and we hope to accelerate the progress towards a treatment."

Because of the multisystem nature of FA, the choice of treatment target presents a challenge for gene therapy. Different routes of administration may be required to treat cardiac and nervous system involvement. There are several other factors of consideration for a gene therapy trial design in FA, including inclusion/exclusion criteria, length of trial, burden on patient/caregiver related to location of the trial and procedures, and risks associated with dose, immunomodulation, and administration method.

"This additional source of funding helps diversify therapeutic approaches to slow, stop, reverse, and ultimately cure Friedreich's ataxia,” Jennifer Farmer, chief executive officer at FARA, said in a statement.1 "Our strategy at FARA has been to fill the pipeline with a range of targeted approaches, and we are grateful for the opportunity to work with Muscular Dystrophy Association and the investigators at UMass Chan Medical School to develop this promising area of research."

1. Muscular Dystrophy Association and Friedreich’s Ataxia Research Alliance announce collaborative research grant using novel gene editing technology to address root cause of Friedreich’s ataxia disease. Muscular Dystrophy Association. April 17, 2024. Accessed April 18, 2024.
2. Friedreich Ataxia. National Institutes of Neurological Disorders and Stroke. Updated March 6, 2024. Accessed April 18, 2024.
3. Trantham SJ, Coker MA, Normal S, et al. Perspectives of the Friedreich ataxia community on gene therapy clinical trials. Molecular Therapy. 2024;32(1):101179. doi:10.1016/j.omtm.2023.101179
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