What is Progressive Muscular Atrophy?
Progressive muscular atrophy (PMA) is a neurological disorder in which degeneration of nerve cells in the spinal cord causes symptoms related to movement, muscle, strength, and movement control. PMA often first affects the muscles of the hands before spreading to other parts of the body.
PMA is one of a group of disorders called motor neuron diseases (MNDs). MNDs affect nerve cells in the brain and the spinal column. These diseases attack motor neurons, the nerve cells that control the movement of muscles throughout the body. MNDs cause the neurons to die slowly over time, and as they do, the patient loses the ability to control or use their muscles.
MNDs are classified according to their origin (inherited or not) and which motor neurons they affect. Some MNDs affect cells in the brain (upper motor neurons), and others affect cells in the brain stem and spinal cord (lower motor neurons). PMA affects the lower motor neurons and is usually not inherited.
PMA is sometimes called Duchenne-Aran disease.
Symptoms of PMA
PMA symptoms usually first affect muscles in the hands and arms, but the symptoms often progress to include the lower body. Common symptoms include:
- Muscle weakness
- Wasting of muscle tissue (atrophy)
- Muscle twitches
- Muscle cramps
- Loss of reflexes
- Difficulty breathing
Difference from ALS
PMA differs from amyotrophic lateral sclerosis (ALS) in that ALS affects both the upper and lower motor neurons, while PMA only affects the lower motor neurons. PMA usually begins earlier than ALS (before age 50) and progresses more slowly. PMA also typically has a somewhat better prognosis than ALS, with nearly two-thirds of PMA patients surviving at least five years after the appearance of symptoms. The 5-year survival rate for ALS is about 37%.
However, as many as 70% of people with PMA eventually experience degeneration of their upper motor neurons, and PMA may progress to ALS. Therefore, some scientists believe that PMA is not a distinct condition, but rather a variant of ALS.
What Causes Progressive Muscular Atrophy?
Scientists don’t precisely know what causes PMA. Although some MNDs are linked to inherited gene mutations, PMA seems not to have an inherited component in most cases. Possible causes of motor neuron degeneration in PMA include exposure to toxins, viral infections, or non-inherited changes in genes.
Is Progressive Muscular Atrophy Hereditary?
Some MNDs, including Kennedy’s disease and spinal motor atrophy (SMA), are inherited, but most cases of PMA do not seem to have an inherited genetic component. Most people with PMA have no family history of the disease or other MNDs.
How Is Progressive Muscular Atrophy Detected?
PMA usually begins in adulthood but tends to emerge earlier than ALS. It is most common in men under the age of 50.
Early signs of PMA may include:
- Weakness in the hands or arms
- Difficulty performing tasks with the hands
- Muscle twitches
- Muscle cramps
How Is Progressive Muscular Atrophy Diagnosed?
When your doctor suspects that PMA might be the cause of early symptoms, they will conduct a variety of tests and exams. Much of the diagnostic process aims to rule out other possible causes of the symptoms rather than directly diagnosing PMA.
- Laboratory tests. Tests of your blood and urine will not necessarily confirm a diagnosis of PMA, but the tests may be able to rule out other conditions that could be causing symptoms.
- Electromyogram (EMG). This test uses electrodes to measure the electrical activity in your muscles as they work. The test can be used to detect abnormalities in muscle function that support a diagnosis of PMA.
- Muscle biopsy. In this test, a small amount of muscle tissue is removed and tested. The biopsy is typically used to detect other diseases and rule out PMA.
- Nerve conduction tests. These tests measure how well your nerves can communicate with your muscles. These tests may detect nerve damage or disorders other than PMA that could be causing symptoms.
PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.
How Is Progressive Muscular Atrophy Treated?
No treatment will stop the progression of PMA or reverse the effects of its symptoms. Treatment for PMA is generally similar to that for ALS. However, riluzole, a medication used to help people with ALS breathe independently, has not been shown to be effective for people with PMA.
Most treatments for PMA aim to reduce the impact of symptoms, improve quality of life, and prevent life-threatening complications.
Therapies that may be used to treat PMA include:
- Physical therapy
- Occupational therapy
- Breathing assistance
- Mobility assistance
- Nutritional support
How Does Progressive Muscular Atrophy Progress?
PMA symptoms worsen over time, but the disorder’s progression is usually much slower than that of ALS. When PMA does not progress to ALS, the patient’s life expectancy is generally longer. However, when ALS develops, muscles that control breathing or swallowing are more likely to be involved, and fatal complications can occur. Possible complications include:
- Difficulty swallowing
- Choking or gagging
- Inhaling food, saliva, or other contaminants into the lungs
- Respiratory infections such as pneumonia
How Is Progressive Muscular Atrophy Prevented?
There is no known way to prevent PMA.
Progressive Muscular Atrophy Caregiver Tips
- Educate yourself about the disease, its effects, and the side effects of medications used to treat it. People with PMA may be at higher risk of developing depression and anxiety. Be on the lookout for the warning signs of these conditions.
- Encourage a healthy lifestyle. There is no cure for PMA, but there are ways to manage symptoms and maintain a good quality of life. Facilitate eating healthy foods and getting as much exercise as possible.
- Join a support group for caregivers. Caregivers are at risk of developing physical and mental health issues, too. So take time for yourself, and get the help you need when you feel overwhelmed.
Progressive Muscular Atrophy Brain Science
Researchers are looking for the causes of PMA, ALS, and other MNDs to understand how the disease affects the brain and for effective treatments for the disease. Current studies include:
- Researchers suspect that a brain-cell protein called membralin might play a role in the development of ALS. Scientists don’t have a complete understanding of what membralin does in the brain’s nerve cells, but they have found evidence that a deficiency of protein may be a cause of ALS and other degenerative nerve diseases. Their studies suggest that gene therapies that increase levels of membralin may have potential as an ALS treatment.
- One clinical study is currently testing a drug that takes a new approach to treating ALS. The drug aims to increase muscle function rather than improve communication between nerves and muscles. The hope is that the drug will help muscles work more efficiently to compensate for the weakness caused by ALS nerve damage. The drug seems particularly effective at helping the muscles that control breathing, and as a result, patients may breathe better for longer.
Progressive Muscular Atrophy Research
Title: HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
Principal investigator: Avindra Nath, MD
National Institutes of Health Clinical Center
Objective: In this Phase I, proof-of-concept study, researchers aim to determine whether an antiretroviral regimen approved to treat human immunodeficiency virus (HIV) infection would also suppress levels of Human Endogenous Retrovirus-K (HERV-K) found to be activated in a subset of patients with amyotrophic lateral sclerosis (ALS). Researchers propose to measure the blood levels of HERV-K by quantitative PCR before, during, and after treatment with an antiretroviral regimen. In addition, researchers will evaluate the safety of the antiretroviral regimen for participants with ALS and also explore clinical and neurophysiological outcomes of ALS symptoms, quality of life, and pulmonary function.
Study Population: Investigators will study a subset of ALS patients with a ratio of HERV-K: RPP30 greater than or equal to 13. About 30% of ALS patients may have detectable levels of HERV-K; about 20% of patients with ALS have a level >1000 copies/ml. To show whether the HERV-K could be suppressed, they will recruit from the approximately 20% of patients with high levels so that the antiretroviral effect can be determined.
Design: This is an open-label study of a combination antiretroviral therapy for 24 weeks in 25 HIV-negative, HTLV-negative ALS patients with a high ratio of HERV-K: RPP30. The study duration for each participant will be up to 72 weeks. Participants will be followed regularly for safety, clinical, and neurophysiological outcomes.
Outcome Measures: The primary outcome measure will be the percent decline in HERV-K concentration measured by quantitative PCR. Percent decline for a patient is measured by: 100 x (screening visit – week 24 visit measurement) / screening visit. The safety of antiretrovirals in volunteers with ALS as measured by the frequency and type of AEs, the ability to remain on assigned treatment (tolerability), physical examinations, laboratory test results, vital signs, and weight/body mass index (BMI). Efficacy will be explored by measuring the change in mean scores of the ALS Functional Rating Scale-Revised (ALSFRS-R), the ALS Specific Quality of Life Inventory-Revised (ALSSQOL-R), the ALS Cognitive Behavioral Screen (ALS-CBS), vital capacity and maximal inspiratory pressure as measured by a handheld spirometer, electrical impedance myography (EIM), the change in neurofilament levels in the blood and/or CSF, and the change in uring p75ECD levels.
Title: Studies in Amyotrophic Lateral Sclerosis (ALS) and Other Neurodegenerative Motor Neuron Disorders
Principal investigator: Bjorn Oskarsson, MD
Mayo Clinic Florida
This study aims to collect, from patients with sporadic and familial ALS and their family members, clinical data and blood samples for extraction of DNA, RNA, preparation of lymphocytes, plasma, and serum to establish a repository for future investigations of genetic contributions to ALS pathogenesis. In addition, blood samples for DNA extraction also would be collected from control subjects with no personal or family history of ALS phenotypes.
Title: CNS10-NPC-GDNF Delivered to the Motor Cortex for ALS
Principal investigator: Richard Lewis, MD
Cedars-Sinai Medical Center
Los Angeles, CA
The investigator is examining the safety of transplanting cells engineered to produce a growth factor into the motor cortex (brain) of patients with Amyotrophic Lateral Sclerosis (ALS). The cells are called neural progenitor cells, a type of stem cell that can become several different types of cells in the nervous system. These cells have been derived to specifically become astrocytes, a type of neural cell. The growth factor is called glial cell line-derived neurotrophic factor, or GDNF. GDNF is a protein that promotes the survival of many types of neural cells. Therefore, the cells are called “CNS10-NPC-GDNF.” The investigational treatment has been tested in people by delivering it to the spinal cord. However, it has only been delivered to the motor cortex of animals. In this study, investigators want to learn if CNS10-NPC-GDNF cells are safe to transplant into the motor cortex (brain) of humans.