Multiple system atrophy (MSA) is a serious neurodegenerative disease with no available disease-altering therapies and no cure. Its natural history covers a 6 to 9 year course, during which the disease progresses to end in certain death. Currently available symptomatic therapies offer some relief, but more options are needed. Any change in outlook for patients with MSA will come from research.
There are several lines of research that could bring relief to people suffering with MSA. Approaches such as small molecule drugs, immunotherapy, and stem cell therapy are all being used to search for new treatments for MSA. Because of the overlap in the biological basis of the diseases, breakthroughs from the study of Alzheimer’s disease, Parkinson's disease, and multiple sclerosis have offered some inspiration for MSA research.
Stem Cell Therapy
One promising approach for MSA is stem cell therapy. Stem cells are immature cells that are capable of developing into many different cell types. Mesenchymal stem cells (MSCs) are derived from the bone marrow. They are already used in the treatment of several diseases, including some neurodegenerative disorders. Growth factors secreted by MSCs have been shown to protect nerve cells against MSA, conferring resistance to the MSA disease process, and also stimulating the regeneration of nerve cells.
Stem cells are either transplanted directly to damaged areas of the brain or infused into the bloodstream to migrate by themselves to the target areas. In 2008, a study of mesenchymal stem cell therapy in a group of MSA patients showed that there was an improvement in symptoms among patients who received therapy compared to those that didn't over a 12 month period. The improvements were achieved in measures of orthostatic hypotension and cerebellar dysfunction.
Another potential strategy to combat MSA is immunotherapy. Antibodies are targeted to bind the defective alpha-synuclein protein, which accumulates in MSA to cause damage to the brain. This involves creating a vaccine against the protein to protect the body against its buildup. Some researchers are studying alpha-synuclein immunotherapy in combination with an anti-inflammatory drug, which is expected to have a synergistic effect.
The Insulin Connection
There are some studies that show a link between insulin resistance and MSA. A similar connection has been identified in Alzheimer’s disease and Parkinson’s disease, leading to positive preclinical results in the trials of a drug used to treat diabetes mellitus. Patients in the trial experienced improvements in motor symptoms and cognition, and a subsequent study showed that the positive effects persisted for one year after the end of the study. MSA shows a similar pattern of dysfunction of insulin receptors to the above disease conditions. For this reason, scientists are now looking at the benefits of using the same diabetes medication for MSA.
Some researchers are investigating drug therapy for MSA. In one study, a multiple sclerosis drug is being tested for effectiveness in MSA, along with two completely new compounds. The goal is to protect the signaling neurons and support the myelinated cells.
Another drug candidate, nicknamed “the molecular tweezer,” is under investigation for MSA after yielding promising results when used to treat Alzheimer's disease and Parkinson's disease. The goal of the project is to prevent or even reverse the formation of alpha-synuclein plaques.
In addition to a search for new treatments, there is still much to be learned about the mechanisms of MSA. Scientists are searching for genetic biomarkers of the disease which could not only assist in diagnosis and to predict the risk, but might also lead to identification of new targets for treatment. Some scientists are also working to better understand how MSA affects the brain through imaging studies.
Reviewed by Dr. Liji Thomas, MD