Phillip A. Low, M.D. has a long-standing research focus on clinical research into the cause and treatment of autonomic disorders. Efforts have been concentrated on three major areas.
Dr. Low's research has been continuously funded by the National Institutes of Health (NIH) over the past 30 years.
Research into the cause, mechanisms and treatment of multiple system atrophy (MSA). Dr. Low heads an NIH-funded program project on MSA. The hallmark of MSA is gial cytoplasmic inclusions due to aggregation of microfibrils of an abnormal protein (alpha-synuclein). The team has been elucidating how this aggregation leads to degeneration of nearby neurons.
Importantly, they have sought approaches that prevent or reverse this process and have tried to apply it to human subjects with MSA. They have an ongoing double-blind, placebo-controlled clinical treatment trial of MSA with rifampicin. Dr. Low heads this NIH-funded, multicenter national study of 100 subjects who are treated for 12 months. Another treatment trial approach is that of mesenchymal stem cells (MSC), based on the hypothesis that MSCs can provide the necessary growth factors that are deficient (due to glial cytoplasmic inclusions).
Dr. Low and his team are also evaluating novel methods to treat other complications of MSA, including orthostatic hypotension. In orthostatic hypotension, the orthostatic fall in blood pressure is coupled with excessively high blood pressure when the person lies down (supine hypertension). Dr. Low and his colleagues are exploring novel approaches, based on their research, that can improve standing blood pressure without aggravating supine hypertension. They also have an ongoing study on the natural history of MSA.
- Development of novel autonomic tests and instruments to study autonomic disorders. Dr. Low's program has been responsible for the development of novel tests that can noninvasively quantitate the severity and distribution of autonomic failure. These include invention of the quantitative sudomotor axon reflex test (QSART) and the development of a test battery that can define how much and how widespread autonomic failure is in a patient. They have coupled these tests with development of test instruments that evaluate symptoms of autonomic dysfunction.
- Diagnosis and treatment of autonomic neuropathies. The third area of focus is on the autonomic neuropathies, such as diabetic autonomic neuropathy, amyloid neuropathy and autoimmune autonomic ganglionopathy. A special focus has been on the development of improved methodology in the diagnosis and treatment of these conditions.
Significance to patient care
Autonomic disorders have been considered the "Cinderella" of medicine, in that they are regarded as quaint, mysterious and untreatable disorders. Dr. Low has helped develop methodology and approaches that enable physicians to accurately diagnose the presence of autonomic disorders and evaluate their severity.
He has coupled these approaches with research to unravel causes of dysautonomias and helped develop novel treatments that improve patient care and recovery of autonomic function. A particular focus has been on the autonomic neuropathies, orthostatic intolerance and the synucleinopathies, especially multiple system atrophy (MSA).
- Robert D. and Patricia E. Kern Professor of Neurology, 2006