Muscle clumping is a condition where abnormal protein aggregation occurs in the muscles. If left untreated, it can cause serious problems, including speech and swallowing problems. It can also lead to respiratory difficulties, which may be life threatening. Some patients may even experience contractures in their joints, which can make walking difficult.
ACETYLATED TDP-43 PROTEINS
A new study by NC State University and UNC School of Medicine has found that an enzyme called acetylation can prevent protein clumping in muscle cells. This enzyme is believed to be a major contributor to muscle weakness caused by amyotrophic lateral sclerosis (ALS). The scientists also gained new insights into how these TDP-43 protein aggregates form, which may lead to new treatments in the future.
The team discovered that acetylation can affect the function of proteins in the muscle, by changing their ability to bind to RNA and DNA. They found that spinal motor neurons from ALS patients had acetylated TDP-43 proteins, which inhibited their ability to connect to DNA or RNA molecules. They now believe that this protein may be a therapeutic target in ALS.
The TDP-43 protein is normally located in the cell nucleus, where it appears to play multiple roles. But in some degenerative diseases, this protein is released from the nucleus and clumps together in the cytoplasm. This process prevents normal gene expression and leads to the death of motor neurons. In turn, this causes the muscles to weaken and deteriorate in strength.
STEROIDS
One of the common treatments for muscle clumping is a course of steroids. This type of medication, which is also called “pro-steroid,” is a powerful anti-inflammatory drug. It is typically prescribed for a short period of time, usually one to two weeks. There are several forms of steroids, including tablets, creams, and injectable solutions. In most cases, the patient begins treatment with a high dose to provide pain relief and tapers off after five or six days.
While steroids are one of the first-line treatments for muscle clumping, they can cause serious side effects, such as suppressing the immune system. Instead, doctors may prescribe other drugs that help reduce the inflammation and are safer for long-term use. These other drugs include methotrexate, azathioprine, ciclosporin, tacrolimus, and mycophenolate.
Another potential side effect of steroids is hirsutism. Although hirsutism is not common, some patients develop it. Some patients will develop a mild rash, while others may experience a significant amount.
MUSCLES BIOPSIES
MUSCLES BIOPSIES are an important step in the treatment of muscle clumping. The physician will select the muscle for biopsy based on your symptoms. MRIs or EMGs can help the doctor locate the area to biopsy. The biopsy site may be tender for two to three days. A pain reliever can help with the soreness.
Muscle biopsies can be performed to identify the causes of muscle clumping. The biopsy shows that the affected muscle is characterized by increased fiber size variability, mild endomysial fibrosis, and rare nuclear internalization. It also reveals rimmed vacuoles and MHCfast positive fibers. The tissue samples also show no overt type grouping and no significant change in the oxidative and acid phosphatase reactions. The biopsy also reveals positive results for neonatal and developmental MHCs, TDP-43, and SMI-31.
Muscle biopsies require a small amount of muscle tissue. They are a useful tool in the diagnosis and treatment of muscle disorders. Patients will be asked to remove all of their clothes for the procedure and will be given a gown to wear. A healthcare provider will then clean the site with an antiseptic solution and insert a needle. The needle may cause a stinging or numbing sensation. Patients may also experience soreness and bruising for a few days. Afterwards, they may be prescribed pain medications.
ANTI-SYNTHETASE SYNDROME
Antisynthetase syndrome is characterized by circulating anti-synthetase antibodies in the blood and muscle tissue. These antibodies include anti-Jo-1 and anti-threonyl (anti-PL7). Symptoms include symmetrical muscle weakness, inflammation of the skeletal muscle and degeneration of muscle fibers.
Anti-synthetase syndrome has been associated with interstitial lung disease, a broad category of inflammatory and scarring of the lung. There are more than 200 conditions associated with interstitial lung disease, and it is important to distinguish between patients with this syndrome and those with other causes of interstitial lung disease. Anti-synthetasis antibodies may be absent or present in patients with interstitial lung disease.
In a case of idiopathic inflammatory myopathy, anti-synthetase antibodies were found in the muscle tissue of a young female patient. The patient was treated with induction therapy consisting of intravenous methylprednisolone, cyclophosphamide, prednisone, and azathioprine. Anti-synthetase antibody therapy is recommended in these cases.