Skin Biopsy Update: The latest news re: efficacy and usefulness in Parkinson’s disease diagnosis, now and in the future
A newly published study assessed the ability of a skin biopsy to diagnose Parkinson’s disease (PD) and related disorders and demonstrated that it was very accurate in distinguishing between those who had the disorders and those who did not.
Research suggests that what underlies the development of PD is the misfolding of a normal protein called alpha-synuclein. Clumps of misfolded alpha-synuclein build up in the brain and interfere with the normal functioning of the brain cells, eventually causing cell death. Phosphorylation, or the attachment of a phosphate group onto the alpha-synuclein molecule, can result in a particularly harmful form of alpha-synuclein. Phosphorylated alpha-synuclein can be found in nerves all over the body of a person with PD including in nerve fibers of the skin.
These nerves can be accessed for study in a lab via a skin biopsy. CND Life Sciences developed the Syn-One Test to detect the phosphorylated form of alpha-synuclein in a set of skin biopsies that are taken from the neck, thigh, and back of the legs as a way of diagnosing disease.
The newly published study reported on the results of a clinical trial funded by the National Institutes of Health to validate the Syn-One Test. The test was positive in 92.7% of people with Parkinson’s, 98.2% of people with Multiple System Atrophy (MSA), and 96% of people with Dementia with Lewy bodies (DLB). A negative test was present in 96.7% of the control subjects. Therefore, the test was accurate in determining both who did and who did not have PD or related disorders.
Because phosphorylated alpha-synuclein accumulates not only in PD, but in DLB and MSA, currently the test can only determine if you have one of these diseases but is not designed to distinguish between these diseases. However, CND Life Sciences has conducted small studies that have shown that the pattern of distribution of the phosphorylated alpha-synuclein is different between the different conditions. Larger studies will need to confirm that before it is used clinically to distinguish between PD and related disorders.
This data supports the use of the skin biopsy test as a biomarker, a measurable characteristic in the body that indicates that disease is present, for PD.
Additional testing options include a test of the cerebral spinal fluid that detects abnormal alpha-synuclein as a biomarker, as well as an imaging test called a DaTSCAN, which can detect a decrease in the nerves in the brain that communicate with dopamine to help diagnose PD and related conditions.
The critical question is – what is the role of these tests in the clinical care of people with PD or suspected PD? It turns out that the clinical features of PD are unique to PD and often very easy to see via a neurologic exam in a doctor’s office. Rest tremor for example, is seen in virtually no other illness. Therefore, in most cases, the clinical exam is very accurate in determining whether a person has PD or not and a confirmatory biomarker test is not necessary. However, there are cases when the clinical exam is not as clear. Currently, movement disorders physicians are considering how to best use biomarker tests in those situations.
In the future, these tests may have a role in determining whether PD is present before the development of the characteristic motor features. This will become particularly important when a medication that slows the progression of the disease is discovered – then the medical community will want to prescribe the medication as early as possible, potentially before motor symptoms are present.
Currently, these tests will be very useful for research purposes – to make sure that the right people are in clinical trials. If the goal of the medication in the clinical trial is to decrease alpha-synuclein clumping, then ensuring that those in the trial have abnormal alpha-synuclein to begin with, is critical.
As always, APDA keeps a close eye on the latest PD research, and we will bring you news as it develops.
We invite you to learn more about APDA’s research program and the work we fund.