A collection of resources for individuals and families affected by Spinocerebellar Ataxia Type 3 (SCA3), also known as Machado-Joseph Disease (MJD).
SCA3 or Machado-Joseph Disease, is caused by a genetic mutation that is passed on from parents to their children. In SCA3, the impairment of nerve cells and nerve fibers causes degeneration of the cerebellum (the coordination center of the brain) and related brain regions. For complete information about symptoms, diagnosis, and treatment of Ataxia, visit our What is Ataxia? page. This page contains NAF’s resources that are specific to SCA3/MJD.
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Presented by Jennifer Faber, MD
SCA3 (also known as Machado-Joseph Disease) is one of the most common types of Spinocerebellar Ataxias. This webinar covers the causes and symptoms of SCA3/MJD, the typical diagnostic journey for those affected, and what to expect for clinical care.
Presented by Hayley McLoughlin, MD, PhD
This webinar covers how SCA3 is studied and gives an overview of the current state of research and drug development for the disease.
This is a visual tool created to show the progress of all SCA3 therapies that are currently being developed. Along the vertical axis, treatments are grouped by their mechanism, or how the drug works. The horizontal axis shows the stage of research where the drug is in development. Phases 1 through 3 involve clinical trials with human participants. Visit the SCA3 Pipeline page for more details.
On September 22, 2023, the FDA hosted a listening session with advocates from the Spinocerebellar Ataxia Type 3 (SCA3) disease community. The National Ataxia Foundation and our partner organizations led efforts to invite SCA3 community members to share their experiences about living with the rare disease. To learn more, visit our SCA3 FDA Patient-Led Listening Session Summary page.
Participating in a research study or clinical trial is one way to take an active role in furthering understanding and treatment of Ataxia. It is also a way to get access to new treatment options before they are widely available. To find studies that are enrolling patients, visit our Help Develop New Treatments page.
SCA3 (also known as Machado-Joseph Disease) is one of the most common types of Spinocerebellar Ataxias. Machado-Joseph disease was identified in 1972, and researchers first described SCA3 in 1983. The discovery of the disease gene revealed that these two are actually the same disease. Although SCA3 was once thought to be very rare and found only in certain isolated ethnic groups, studies have since shown that SCA3 may be the most common dominantly inherited Ataxia in many regions of the world. The ratio varies among populations depending on geographical location and ethnic background.
SCA3 is marked by incoordination. Impaired balance is usually the first symptom, followed later by incoordination of the hands and slurring of speech. Some individuals with SCA3 will notice double vision, and an examining physician might note limitation of eye movements, abnormally slow eye movements, or a “staring” appearance of the eyes. As the disease progresses, it is common to experience spasticity, rigidity, loss of muscle bulk and strength, and slowness of movement. In general, SCA3 symptoms tend to be more wide-ranging than those in many other forms of Ataxia.
The age of onset and the range of symptoms can vary widely in SCA3, even among affected persons in the same family. This variability reflects the type of disease-causing genetic defect in SCA3; an expansion of a DNA triplet repeat. The repeat expansion is SCA3 varies in size among affected persons. In general, the longer the repeat the more powerful the effect of the mutation, resulting in earlier onset of the disease. The greater the expansion, the more severe the disease is likely to be.
The symptoms of SCA3 usually appear in middle adult life and progress over several decades, with some patients surviving for almost 30 years after the onset of symptoms. Onset in adolescence or as late as age 70 can also occur. This extreme range is age of onset reflects difference in the size of the disease-causing DNA repeat.
SCA3 is a genetic disorder which means that it is an inherited disease. The abnormal gene responsible for this disease is passed from generation to generation by family members who carry it. Genes are heritable microscopic structures that comprise our genetic makeup and contain instructions for the features a person inherits from his or her parents. Genetic diseases like SCA3 occur when there is an abnormal change or mutation in the DNA that makes up one of the body’s 20,000 genes.
In SCA3, the mutation is an expansion of a DNA triplet repeat in the ATXN3 gene. Genes are made up of molecules known as nucleotides linked together in highly ordered chains. Each nucleotide is identified by one of four letters (C, A, G, or T). In SCA3, the mutation results in extra copies of a triplet repeat of the nucleotides C-A-G. Thus, SCA3 is due to a CAG repeat expansion. SCA3 is inherited in a dominant fashion which means that it passes directly from one generation to the next without skipping generations. Each child of a person with SCA3 has a 50 percent chance of inheriting the disease gene that causes SCA3. Individuals of either gender are equally likely to inherit the gene and develop the disease.
A neurologic examination can determine whether a person has symptoms typical of SCA3, and a simple gene test can accurately detect the presence of the mutation that causes the disease. A neurologist is often the most helpful specialist in determining the cause of symptoms that might indicate SCA3. Most people who develop SCA3 have a family history of Ataxia with similar symptoms which is an important clue to the diagnosis. It is important to rule out other diseases and to consider forms of Ataxia. When SCA3 is suspected, DNA-based testing can confirm the diagnosis. The DNA test for SCA3 involves analysis of the mutation in the ATXN3 gene.
NAF is offering free virtual genetic counseling and genetic testing for individuals who are at-risk for SCA3. Genetic testing to confirm a diagnosis of Ataxia can be an incredibly useful tool for persons with a family history of Ataxia. It can help inform decisions around family planning, healthcare/lifestyle choices, and professional/financial planning. Genetic testing is also often a requirement for participation in clinical trials for SCAs. Individuals who have a direct relative who has genetically tested positive for SCA3 are eligible. If you are interested in participating, please contact NAF’s Research Manager, Kelsey Trace at email@example.com.
SCAsource provides Ataxia research news, directly from researchers to the Ataxia community. Visit SCAsource to see their full collection. Here is a collection of articles about SCA3.
Written by Dr. Gülin ÖzEdited by Dr. Celeste Suart Advanced Magnetic Resonance Imaging (MRI) detects brain changes before ataxia symptoms. The list of pharmaceutical companies that turned their attention to Read More…
Written by Dr. Ambika Tewari Edited by Dr. Larissa Nitschke The abnormal activity of cells in the deep cerebellar nuclei and Purkinje cells correlate with the early onset of motor Read More…
Written by Kaitlyn NeumanEdited by Dr Chandana Kondapalli To induce cell death, or to degrade sick mitochondria – that is the question: a new role for ataxin-3 as a mediator Read More…