The first inkling that maybe something wasn't quite right came when Cameryn Cobb, then 14, fell off the starting block before a swim meet. The next time was when she tumbled after stepping down from the bleachers to take communion at her Catholic high school.

Initially, Cobb's doctors and parents chalked up her clumsiness to a concussion—she had passed out previously from dehydration in band class and hit her head. But when she went to get her driver's permit the following year, she failed the eye exam and ended up seeing a retina specialist, who diagnosed her with a form of macular degeneration.

That diagnosis still didn't explain Cobb's gait and coordination problems, which continued to accelerate. So her family started searching for other explanations. Their quest led to a neurologist who conducted a thorough exam and medical history and diagnosed Cobb with spinocerebellar ataxia type 7 (SCA7), a hereditary form of ataxia.

Ataxia refers to any disorder that affects coordinated movement such as walking, talking, playing the piano, or riding a bike, says Albert La Spada, MD, PhD, director of the Duke Center for Neurodegeneration and Neurotherapeutics at the Duke University School of Medicine in Durham, NC. Ataxia occurs when nerve fibers that transmit messages to and from the brain are impaired, resulting in degeneration of the cerebellum, the brain region most important for coordinated movement.

Acquired ataxias are caused by anything that injures the cerebellum, including stroke, head trauma, brain tumors, autoimmune diseases, infections, exposure to toxic substances, alcohol abuse, or vitamin deficiencies. Ataxia may be a symptom of other neurologic disorders that affect the cerebellum, such as multiple sclerosis or multiple system atrophy.

By contrast, hereditary ataxias are the result of genetic mutations. "They can prevent a gene from producing a necessary protein, cause the gene to produce a damaged or underactive protein, or allow the gene to produce an altered protein toxic to the cell in which it is produced," says Susan L. Perlman, MD, director of the Ataxia Center and Huntington's Disease Society of America's Center of Excellence at UCLA.

Unlike acquired forms of ataxia, inherited ataxias are progressive and incurable and affect not just the patient but also family members who might inherit the mutated gene. Inherited ataxias are typically more severe and tend to appear at an earlier age. "As a rule of thumb, the disease progresses more rapidly in younger patients," says Dr. La Spada.

There are two types of inherited ataxias: autosomal dominant and autosomal recessive. The former has a 50 percent chance of transmission from parent to child; the latter, a 25 percent chance. "We're up to nearly 50 inherited forms of dominant ataxias, which we call spinocerebellar ataxias, or SCAs," Dr. La Spada says. "Recessive ataxias have various names. One of the most common is Friedreich's ataxia."

Cobb has an autosomal dominant ataxia and has tested positive for the genetic mutation associated with SCA7, but neither of her parents has the disease—although they have not been tested for the genetic mutation—and there is no known family history. However, spontaneous mutations are not rare and can account for the occasional individual with an autosomal dominant genetic disorder without a family history, says Gary Gronseth, MD, FAAN, chair of neurology at the University of Kansas Medical Center in Kansas City.

Now 19, Cobb is often unsteady on her feet and sometimes requires a wheelchair. She also has trouble being understood when she speaks. But the toughest part of her diagnosis was giving up sports. "It was very hard not being an athlete anymore," Cobb says. "I swam almost every day for years, and to have it taken away really changed my life."

Still, Cobb makes the best of her circumstances. She enjoys spending time with friends and manages to stay upbeat. She even went to her prom last year. "My prom date was very helpful," she says. "He held on to me the entire night."

Disease Course

Regardless of the kind of ataxia, symptoms are largely the same. They usually start with gait problems, similar to the effect that alcohol has on motor performance. "It's a wide, staggering gait," says Vikram Shakkottai, MD, PhD, clinical director of the ataxia program at the University of Michigan in Ann Arbor. People may need to use walls or a cane for support while walking in the early stages and a wheelchair as the disease progresses, he says. In most cases, a person with inherited ataxia will eventually need a wheelchair.

Ataxia also disrupts small, precise movements that could involve the limbs, the hands, or the muscles used for speaking and seeing. "There's no loss of strength, but there is a loss of coordination," Dr. Shakkottai says. "Speech may be slurred or halting and less comprehensible over time. The eyes don't move precisely, and there's often a phenomenon known as nystagmus, in which the eyes bob up and down or jiggle when looking at objects." In Friedreich's ataxia (which occurs mostly in children), diabetes and cardiac problems, such as heart failure and heart rhythm abnormalities, are common as well.

The life expectancy of people with inherited ataxias depends on the form of ataxia they have, but for most it is shorter than normal. "In the case of Friedreich's, it's because the heart is affected," says Harry T. Orr, PhD, professor of genetics at the University of Minnesota Medical School in Minneapolis. "In many other ataxias, it is because the region of the nervous system that controls swallowing and coughing is affected. Patients may have problems with recurrent pneumonia due to aspiration [breathing in food particles] while eating."

Patients with ataxia often exhibit symptoms for years before they are diagnosed, and they are frequently misdiagnosed. "It's very variable, but often patients have seen multiple other providers beforehand, and it takes 10 or more years to get a diagnosis," says Dr. Shakkottai. Abnormalities on a neurologic examination, brain scan, or other neurologic testing can indicate ataxia, but an official diagnosis can only be made by a genetic test, says Dr. Perlman.

That could present challenges, however. "There are more than 300 different genetic forms of ataxia," says Dr. Shakkottai. "It's sometimes difficult for a general neurologist with no specific expertise in genetics or ataxia to figure out the right approach to make a diagnosis."

Genetic testing is expensive and may not be covered by insurance. But it's important for several reasons, Dr. Shakkottai says. "Sporadic autoimmune forms of ataxia can present in a similar way to the genetic forms of ataxia and are treatable, particularly when identified early," he says. Drugs that suppress the immune system or significantly reduce its strength, such as tacrolimus (Envarsus) and rituximab (Rituxan), might reverse or prevent progression in those cases. A small subset of inherited ataxias associated with a deficiency in vitamin E also respond to enzyme supplements or high doses of the vitamin.

Many people with ataxia undergo genetic testing to help them plan for the future. "I've had patients say they would make different choices if they knew they had the disease," says Dr. Shakkottai. Testing also can affect decisions on parenthood. To avoid passing on the disease, carriers of the mutation may decide to not have children, to adopt, or to use egg or sperm donors. If they are doing in vitro fertilization, they may have the egg and sperm genetically tested before implantation. Or patients may decide to terminate the pregnancy after prenatal diagnosis.

Managing Symptoms

No medications are approved by the US Food and Drug Administration for inherited ataxias, but several are used off-label to treat symptoms. Two that have the most scientific data behind them for use in ataxia, says Dr. Perlman, are riluzole (Rilutek), which is approved for amyotrophic lateral sclerosis (ALS), and dalfampridine (Ampyra), which can improve walking in people with multiple sclerosis (MS). Riluzole blocks the release of a compound called glutamate, a neurotransmitter that may injure nerve cells in certain situations. Dalfampridine may improve balance.

"Drugs for tremor, muscle spasticity or rigidity, and dizziness, which can complicate ataxia, are also helpful," Dr. Perlman says. Patients with SCA2 and SCA3, whose symptoms look a lot like Parkinson's disease, may benefit from the Parkinson's medication levodopa, says Dr. Shakkottai. "The drug can improve walking in these patients to the extent that they may no longer need an assistive device." But as ataxia progresses, levodopa's effect is likely to wane.

Treatments other than medications also can help patients with ataxia. "Combining medications that treat symptoms with physical, speech, and occupational therapy can improve quality of life," says Deborah Hall, MD, PhD, director of the movement disorder program at Rush University Medical Center in Chicago.

Balance training can be particularly helpful, says Dr. Shakkottai. In a small study of a home-based balance training program, published in Neurorehabilitation Neural Repair in 2015, people with ataxia saw statistically and clinically significant benefits—including greater walking speeds and stride lengths—over the six-week study period.

Furthermore, disease progression may be slowed by lifestyle choices. "Even if we don't have a magic bullet at the moment, it's important to have healthy nutrition, to be physically active as long as it is safe to do so, to be mentally active, and to maintain a good social network," says Stefan Pulst, MD, FAAN, chair of the department of neurology at the University of Utah in Salt Lake City. Dr. Hall adds, "Many times, with good general health, the disease progresses slowly over many years." Meanwhile, support groups for patients and their families can provide emotional and psychological strength.

Adequate sleep is critical too. "A good night's sleep is neuroprotective, because while we sleep our brains are performing a self-cleaning function," says Dr. La Spada. "Neuronal connections and synapses are also being pruned and refined."

Gene Studies

There are some promising leads in ataxia research. For example, scientists are examining "gene blockers" that prevent the production of a damaged protein, says Dr. Perlman. Other areas of inquiry include replacing the mutated gene with a normal copy; identifying small molecules (often in available drugs for other diseases) that could make the mutant gene behave more normally; and developing drugs that remove damaged proteins from nerve cells, protect the nerve cells from genetic damage, or stimulate damaged nerve cells to work better.

Perhaps the most compelling area of research involves molecules called antisense oligonucleotides (ASO)—DNA-like material that is synthesized in the lab to bind to a mutant gene's RNA in order to inactivate it. "These small nucleotides have to be delivered into the spinal fluid," says Dr. Shakkottai. "They target the mutant gene to suppress that gene's function."

Research on ASO therapies for Huntington's disease recently moved into a phase 3 trial. ASOs have also been designed to treat spinal muscular atrophy (SMA), a pediatric neurologic disorder, says James Peter Orengo, MD, PhD, assistant professor of neurology at Baylor College of Medicine in Houston. "ASOs are well along in the development pipeline for a number of the SCAs," says Dr. La Spada. "These therapies destroy the RNA that leads to the production of the protein that is misfolded and causes the pathology."

Dr. La Spada's own lab is conducting animal studies to develop an ASO therapy for SCA7. "I believe that many ASOs will be tested over the next three to five years, and I also predict that at least a few, if not more, will be approved."

That gives patients like Cameryn Cobb something to hope for. She is doing her part by raising money to boost awareness of her disease and support research. She has spoken at a scientific meeting for the National Ataxia Foundation and helped raise $26,000 for the foundation last year. "I want doctors to find a cure," she says.

Ataxia Resources

Friedreich’s Ataxia Research Alliance, 484-879-6160
(The alliance is a resource for patients and families with Friedreich’s ataxia only.)

National Ataxia Foundation, 763-553-0020

National Organization for Rare Disorders, 800-999-6673, 844-259-7178 (for information in Spanish)

Clinical Trials and Patient Registries for Inherited Ataxias

To enroll in a trial, visit clinicaltrials.gov and type “inherited ataxia” or “spinocerebellar ataxia” and “recruiting” in the search field. Here are a sample trial, a readiness trial, and a patient registry.

Drug Trial

• What: Biohaven Pharmaceuticals is recruiting adult patients for a study of the drug troriluzole’s effectiveness at controlling symptoms of spinocerebellar ataxias (SCAs).
• Where: This is a multicenter study.
• When: Ongoing
• For more information: Email Robert Berman, MD, at clinicaltrials@biohavenpharma.com or call 203-404-0410; clinicaltrials.gov

Clinical Readiness Trial

• What: The National Ataxia Foundation seeks individuals with early-stage and symptomless SCA1 or SCA3—or with a first-degree relative diagnosed with SCA1 or SCA3—for ReadiSCA, a clinical readiness trial that aims to validate imaging signs and prepare for future treatment trials.
• Where: This is an international multi-institutional study.
• When: Ongoing
• For more information: Email Sue Hagen, patient and research services director, at susan@ataxia.org or call 763-231-2742; clinicaltrials.gov

Patient Registry 

• What: To identify biomarkers in people with SCA3, the University of Michigan is recruiting patients for a registry.
• Where: Ann Arbor, MI
• When: Ongoing
• For more information: Email Tasha Kaiser at kaisert@med.umich.edu or call 734-232-6247; clinicaltrials.gov