Friedreich’s ataxia is a rare inherited disorder that affects the nervous system, leading to progressive difficulties with movement and coordination. While there is no cure yet, treatment options have evolved significantly in recent years, offering new hope for managing symptoms and slowing disease progression.

How Treatment Approaches Work for Friedreich’s Ataxia

The main goal of treating Friedreich’s ataxia is to help people maintain their quality of life for as long as possible. Treatment does not cure the disease, but it can slow down how quickly symptoms worsen, manage complications, and help patients stay active and independent. Because Friedreich’s ataxia affects each person differently, treatment plans need to be tailored to individual needs and adjusted as the disease progresses over time.^[1]

The approach to treatment depends on several factors, including when symptoms first appeared, how severe they are, and what complications have developed. Some people develop symptoms in childhood or their teenage years, while others may not experience problems until they are adults. This timing affects which treatments doctors recommend and how aggressively they need to manage the condition.^[3]

Standard treatments approved by medical societies have been available for years to manage specific symptoms and complications of Friedreich’s ataxia. These include therapies for heart problems, diabetes, and difficulties with movement. More recently, researchers have developed new medications specifically designed to target the underlying causes of the disease. These newer treatments represent an exciting shift from simply managing symptoms to potentially slowing down the disease process itself.^[2]

Clinical trials play a crucial role in finding better treatments for Friedreich’s ataxia. These research studies test new medications and therapies to see if they are safe and effective before they can be approved for widespread use. People with Friedreich’s ataxia who participate in clinical trials may gain access to promising new treatments while also contributing valuable information that helps advance medical knowledge for everyone affected by this condition.^[9]

Standard Treatments Used Today

For many years, doctors focused on managing the symptoms and complications of Friedreich’s ataxia rather than treating the disease itself. This approach, called symptomatic treatment, remains an important part of care today. It involves using medications and therapies that address specific problems as they arise, helping patients maintain function and prevent serious complications.^[1]

Managing Heart Complications

Heart disease is one of the most serious complications of Friedreich’s ataxia and is the most common cause of death in people with this condition. Many patients develop cardiomyopathy, which means the heart muscle becomes abnormally thick and cannot pump blood effectively. Others experience irregular heartbeats, called arrhythmias. Standard treatments for these heart problems are the same medications used for other patients with similar cardiac conditions.^[1]

Doctors prescribe medications to help the heart pump more efficiently, control heart rhythm, and prevent fluid buildup in the body. One medication that has been studied specifically for Friedreich’s ataxia is propranolol, a drug that blocks certain stress hormones. In at least one case report, high doses of propranolol helped reduce the thickness of the heart walls and normalized abnormal heart rhythms. However, this treatment needs more research before it can be widely recommended.^[11]

Regular monitoring by a cardiologist is essential for all people with Friedreich’s ataxia, even if they do not have symptoms of heart disease. Early detection of cardiac problems allows doctors to start treatment before complications become severe.^[3]

Diabetes Management

About three out of ten people with Friedreich’s ataxia develop diabetes because the disease damages cells in the pancreas that produce insulin. When this happens, doctors use the same standard diabetes treatments that work for other patients. This includes medications to help control blood sugar levels, dietary changes, and regular monitoring of blood glucose. Managing diabetes well is important to prevent additional complications that could further reduce quality of life.^[3]

Physical and Occupational Therapy

Physical therapy is one of the most important parts of treatment for Friedreich’s ataxia. Regular exercise helps maintain muscle strength and coordination for as long as possible. Physical therapists design exercise programs that focus on balance, coordination, and core stability. Even though the disease causes progressive weakness, staying physically active can slow down the loss of function and help people remain mobile longer.^[3]

Occupational therapy helps patients learn new ways to perform daily activities as their coordination and strength decline. Occupational therapists recommend assistive devices and teach techniques that make tasks like eating, dressing, and bathing easier and safer. This type of therapy is crucial for maintaining independence and preventing injuries from falls.^[18]

Speech therapy addresses problems with speaking and swallowing that often develop as Friedreich’s ataxia progresses. Speech therapists work with patients to improve communication and teach safe swallowing techniques to prevent choking or food going into the lungs, which can cause pneumonia.^[4]

Medications for Coordination and Energy

Some doctors have tried using medications to improve coordination and reduce fatigue in people with Friedreich’s ataxia. One such medication is 5-hydroxytryptophan, a substance that the body uses to make serotonin, a chemical messenger in the brain. The idea behind using this drug was that Friedreich’s ataxia might involve a deficiency of serotonin in the part of the brain that controls coordination. Studies showed that this medication could partially improve cerebellar symptoms, though the effects were modest and not clinically major. Some research suggested it might help stabilize posture with long-term use, but more studies are needed.^[11]

Antioxidant Supplements

Coenzyme Q and vitamin E are antioxidants that have been used to treat Friedreich’s ataxia for many years. The rationale for using these supplements is that they might protect cells from damage caused by toxic substances that build up when mitochondria do not work properly. In one study of ten patients who took high doses of both coenzyme Q (400 mg per day) and vitamin E (2100 IU per day), researchers observed a slowing of disease progression and significant improvement in heart function.^[11]

Another antioxidant called idebenone has been studied more extensively. Idebenone is a derivative of coenzyme Q that may limit the toxic effects of iron on mitochondria. Several studies have assessed whether idebenone can improve neurological symptoms or heart function. The evidence has been mixed, with some studies showing modest benefits and others showing little effect. Idebenone is not currently approved for Friedreich’s ataxia in the United States, though it is available in some other countries.^[11]

Surgical Treatments

Surgery is sometimes necessary to treat complications of Friedreich’s ataxia. About 70 percent of people with the condition develop scoliosis, which is an abnormal curvature of the spine. When scoliosis becomes severe, it can interfere with breathing and cause pain. In these cases, surgeons may perform corrective surgery to straighten the spine and prevent further problems.^[4]

Treatment duration for standard therapies varies greatly. Physical therapy and exercise programs are typically lifelong commitments, with patients needing to continue these activities indefinitely to maintain their benefits. Medications for heart disease and diabetes are also long-term treatments that patients take for years or even decades. The specific combination of treatments and how long they are used depends on which complications develop and how the disease progresses in each individual.^[14]

New Treatments Being Tested in Clinical Trials

The search for therapies that can stop, delay, or reverse Friedreich’s ataxia has accelerated dramatically in recent years. Scientists now understand much more about what causes the disease at the molecular level, which has opened up new possibilities for targeted treatments. Clinical trials are testing several promising approaches, each designed to address different aspects of the disease.^[9]

Omaveloxolone: The First Approved Treatment

In 2023, the United States Food and Drug Administration approved omaveloxolone, marketed under the brand name Skyclarys, as the first medication specifically for treating Friedreich’s ataxia. This approval marked a historic moment for the Friedreich’s ataxia community and for rare disease research in general. Omaveloxolone is approved for people aged 16 years and older who have been genetically confirmed to have Friedreich’s ataxia.^[12]

Omaveloxolone works by activating a protein called Nrf2, which is like a master switch that turns on protective genes inside cells. When Nrf2 is activated, it reduces oxidative stress and inflammation in neurons. Oxidative stress is a type of cellular damage caused by toxic byproducts that accumulate when cells cannot produce energy efficiently. By reducing this damage and inflammation, omaveloxolone helps neurons function better and may slow down the progression of neurological symptoms.^[11]

The approval of omaveloxolone was based on results from a clinical trial called MOXIe Part 2. This was a Phase III study, which means it compared the new drug against a placebo (an inactive pill) to see if the drug truly worked better than doing nothing. Patients enrolled in this trial had genetically confirmed Friedreich’s ataxia and moderate disability levels. They were randomly assigned to receive either omaveloxolone at a dose of 150 mg daily or a placebo pill.^[11]

Researchers measured the effects of treatment using a scale called the modified Friedreich’s Ataxia Rating Scale, or mFARS. This scale measures various aspects of neurological function, including coordination, walking ability, speech, and other motor skills. Lower scores on this scale indicate better function. After 48 weeks of treatment, patients taking omaveloxolone had statistically significant lower mFARS scores compared to those taking placebo, meaning they had less impairment. The difference between the two groups was -2.41 points with a p-value of 0.0138, indicating the result was very unlikely to be due to chance.^[11]

Follow-up studies showed that the benefits of omaveloxolone persisted over longer periods. After 72 weeks and even 124 weeks of treatment, patients continued to show improvement in motor function compared to what would be expected without treatment. Omaveloxolone is taken as a once-daily oral pill, making it relatively convenient for patients to use.^[11]

The approval process for omaveloxolone highlighted the importance of having sensitive outcome measures that can detect changes in a slowly progressive disease. It also demonstrated the crucial role of natural history studies, which track how the disease progresses in untreated patients over time. These natural history studies provided a comparison group that helped researchers understand whether the changes seen with omaveloxolone were truly meaningful.^[9]

Approaches to Improve Mitochondrial Function

Many experimental treatments being tested in clinical trials focus on improving how mitochondria work. Mitochondria are the parts of cells that produce energy, and they do not function properly in Friedreich’s ataxia because of the lack of frataxin protein. Several different strategies are being pursued to help mitochondria work better despite the frataxin deficiency.^[9]

Some trials are testing newer and more potent antioxidants than those used in the past. These medications work by neutralizing the toxic byproducts that damage cells when mitochondria are not working efficiently. Other approaches focus on improving the function of specific enzyme systems inside mitochondria that are disrupted in Friedreich’s ataxia.^[9]

Increasing Frataxin Protein Levels

Since Friedreich’s ataxia is caused by a lack of frataxin protein, one obvious approach is to find ways to increase frataxin levels. Several different strategies are being tested in clinical trials to accomplish this goal.^[9]

Gene therapy is one of the most promising approaches for increasing frataxin. In gene therapy, researchers use a harmless virus to deliver a working copy of the FXN gene into cells. Once inside the cell, this new gene can produce normal frataxin protein. Early-phase clinical trials are testing whether gene therapy is safe and whether it can increase frataxin levels enough to make a clinical difference. These trials are typically Phase I or Phase II studies, which means they focus on safety and preliminary evidence of effectiveness rather than proving the treatment works better than existing options.^[9]

Another approach involves using medications that can increase the activity of the person’s own FXN gene. Even though the gene is damaged in Friedreich’s ataxia, it is still present and can produce small amounts of frataxin. Some experimental drugs can enhance the gene’s activity, allowing cells to make more frataxin from the defective gene they already have. This approach is being tested in multiple clinical trials at various phases.^[9]

Modulating Metabolic Pathways

Frataxin protein does not just affect energy production; it also controls several metabolic pathways inside cells, particularly those involving iron and sulfur. When frataxin levels are low, these pathways become disrupted, leading to an accumulation of iron inside mitochondria. This excess iron contributes to oxidative damage and cell death. Some experimental treatments aim to remove excess iron from mitochondria while simultaneously supporting other metabolic processes that frataxin normally regulates.^[11]

Researchers have shown that therapeutic approaches combining iron removal with treatments that increase frataxin expression may be more effective than either strategy alone. This combination approach addresses multiple problems simultaneously and may produce better results than targeting just one aspect of the disease.^[11]

Understanding Clinical Trial Phases

Clinical trials for Friedreich’s ataxia, like trials for any disease, progress through several phases, each with a specific purpose. Understanding these phases helps patients and families know what to expect when considering trial participation.^[10]

Phase I trials are the first time a new treatment is tested in humans. These studies enroll small numbers of participants and focus primarily on safety. Researchers want to know what dose is safe, how the body processes the drug, and what side effects might occur. Phase I trials for Friedreich’s ataxia typically last a few months and provide crucial information about whether it is safe to proceed with further testing.^[9]

Phase II trials test whether a treatment actually works and continues to monitor safety. These studies enroll more participants than Phase I trials and measure specific outcomes related to the disease, such as changes in the mFARS score, cardiac function, or quality of life measures. Phase II trials help researchers determine the optimal dose and identify which patients are most likely to benefit from the treatment.^[9]

Phase III trials are large studies that compare the new treatment against the current standard of care or a placebo. These trials provide the strongest evidence about whether a treatment is effective and safe enough to be approved by regulatory authorities like the FDA. The MOXIe study of omaveloxolone was a Phase III trial. Phase III trials typically enroll hundreds of patients and last for one to several years.^[11]

Phase IV trials occur after a treatment has been approved. These studies continue to monitor the treatment’s safety and effectiveness in larger numbers of patients over longer periods of time. Phase IV trials can identify rare side effects that were not detected in earlier trials and provide information about how well the treatment works in real-world conditions.^[9]

Where Clinical Trials Are Happening

Clinical trials for Friedreich’s ataxia are conducted at specialized medical centers around the world. In the United States, trials are often conducted at institutions that are part of the Friedreich’s Ataxia Global Clinical Consortium, which brings together expert clinicians and researchers who focus specifically on this disease. Children’s Hospital of Philadelphia, for example, served as a lead study site for the omaveloxolone trials that led to FDA approval.^[12]

Trials are also conducted in Europe, particularly in countries like the United Kingdom, Germany, and France, where there are established centers of excellence for ataxia research. Some trials are international, enrolling patients from multiple countries to reach the necessary number of participants more quickly.^[9]

Eligibility for clinical trials varies depending on the specific study. Most trials require genetic confirmation of Friedreich’s ataxia, meaning patients must have test results showing mutations in the FXN gene. Many trials also have requirements about disease severity, often enrolling patients who can still walk independently or who fall within a specific range of disability. Age restrictions are common, with some trials limited to adults and others specifically designed for children or adolescents.^[10]

Most Common Treatment Methods

• Symptomatic Management
  • Standard medications for heart failure, cardiomyopathy, and arrhythmias to manage cardiac complications
  • Diabetes medications and blood sugar monitoring for patients who develop diabetes
  • Surgical correction for severe scoliosis when spinal curvature interferes with breathing or causes pain
• Rehabilitation Therapies
  • Physical therapy with exercises focused on balance, coordination, core stability, and maintaining muscle strength
  • Occupational therapy to learn adaptive techniques for daily activities and recommend assistive devices
  • Speech therapy to address slurred speech and swallowing difficulties
• Antioxidant Approaches
  • Coenzyme Q combined with vitamin E to protect cells from oxidative damage
  • Idebenone, a coenzyme Q derivative, studied for effects on neurological and cardiac symptoms
  • Omaveloxolone (Skyclarys), an FDA-approved Nrf2 activator that reduces oxidative stress and inflammation in neurons
• Experimental Gene and Molecular Therapies
  • Gene therapy using viral vectors to deliver working copies of the FXN gene to cells
  • Medications designed to increase frataxin gene expression from the person’s own defective gene
  • Treatments targeting iron metabolism and mitochondrial function
• Supportive Care
  • Assistive devices including wheelchairs, walkers, and hearing aids to maintain independence
  • Regular monitoring by a multidisciplinary care team including neurologists, cardiologists, endocrinologists, and other specialists
  • Mental health support through counseling or therapy to address the emotional challenges of living with a progressive disease