The National Institute of Neurological Disorders and Stroke (NINDS) conducts MJD research in its laboratories at the National Institutes of Health (NIH) and also supports MJD research through grants to major medical institutions across the country. Ongoing research includes studies to better understand the genetic, molecular, and cellular mechanisms that underlie inherited neurodegenerative diseases such as MJD. Clinical trials include investigating treatments for SCAs including MJD, identifying biomarkers (signs that can be used to diagnose a disease and monitor its progression), a natural history study of and genetic modifiers in the SCAs, and developing a patient registry for rare diseases, including the SCAs, to allow individuals with these disorders and researchers to connect as easily as possible to help advance treatments and cures for rare diseases including the spinocerebellar ataxias. Other research includes work to better understand the molecular mechanisms involved with SCAs, improve current diagnostic procedures, and develop disease-modifying and other therapies for the spinocerebellar ataxias.
Information from the National Library of Medicine’s MedlinePlus
Machado-Joseph disease (MJD), which is also called spinocerebellar ataxia type 3, is a rare hereditary ataxia (ataxia means loss of control and coordination of the muscles we can willingly move). The SCAs involve loss of structure and function (degeneration) of the cells of the hindbrain, which includes the cerebellum (the part of the brain that helps control muscle movement and balance), the brain stem and upper part of the spinal cord, and sometimes other parts of the nervous system. There are more than 30 distinct types of SCA, which are numbered in order of the discovery of the gene mutation that causes each type.
Depending on the type of SCA, symptoms appear most often in adulthood but can appear in childhood. Several SCAs may have their own clinical signs, but most include:
- Progressive loss of coordination and balance
- Progressive lack of coordination in the arms and legs, including tremor
- Slowness of movement
- Problems with walking (gait)
- Decreased muscle tone
- Vision problems, particularly with focusing the eyes and unwanted eye movements
- Difficulty with speaking (dysarthria) and swallowing (dysphagia)
- Problems with thinking, remembering, and concentration
There are different types of Machado-Joseph Disease:
- Type I is characterized by onset between about 10 and 30 years of age, with faster progression and more dystonia and rigidity than ataxia.
- Type II, the most common type, generally begins between the ages of about 20 and 50 years, has an intermediate rate of progression, and causes various symptoms, including prominent ataxia, spastic gait, and enhanced reflex responses.
- Type III has the latest onset of disease (beginning between approximately 40 and 70 years of age) which progresses relatively slowly and is characterized as much by peripheral neuromuscular involvement (muscle twitching, weakness, atrophy, and abnormal sensations such as numbness, tingling, cramps, and pain in the hands and feet) as by ataxia.
The disease is characterized by slowly progressive clumsiness and weakness in the arms and legs, spasticity, problems with walking, difficulty with speech and swallowing, involuntary eye movements, double vision, and lower limb spasticity. Some individuals also have dystonia (sustained muscle contractions that cause twisting of the body and limbs, repetitive movements, abnormal postures, and rigidity) or symptoms similar to those of Parkinson's disease. Others have twitching of the face or tongue, sleep problems, or neuopathy. Almost all individuals with MJD experience vision problems, including inability to control eye movements.
There is no definitive treatment to cure SCA or slow its progression. Machado-Joseph Disease is incurable, but some symptoms of the disease can be treated. For those individuals who show parkinsonian features, levodopa therapy can help for many years. Treatment with antispasmodic drugs, such as baclofen, can help reduce spasticity. Botulinum toxin can also treat severe spasticity as well as some symptoms of dystonia. Speech problems and trouble swallowing can be treated with medication and speech therapy. Physiotherapy can help patients cope with disability associated with gait problems. Physical aids, such as walkers and wheelchairs, can assist with everyday activities. Special glasses can help with vision problems.
The types and severity of symptoms vary among these ataxias. Spinocerebellar ataxia is progressive, meaning the symptoms worsen with time. Some forms of Machado-Joseph Disease may progress slowly over a period of years, while others worsen within months. Generally, people with SCA will require a wheelchair within 10 to 20 years of diagnosis. SCA can be fatal but some people with the disease have a normal life span.