Funded Studies
Objective/Rationale:
CNP is a peptide produced by brain tissues where it acts to promote growth of nerve cells and their connections. Recent research in healthy humans has identified high concentrations of CNP products in the fluid bathing and nourishing the brain (cerebrospinal fluid, CSF). Surprisingly, much lower amounts of CNP products have been found in CSF drawn from subjects with Parkinson’s disease (PD). This project aims to verify these preliminary findings by studying a larger group of untreated subjects and to relate the levels to disease progression.
Project Description:
Using the DATATOP specimens of stored CSF, we will first analyse a small set of CSF samples to ensure that CNP products have not been degraded during storage. We will also determine whether the site of sampling the CSF circulation affects concentrations. Once these questions have been addressed we will analyse CNP products drawn from 100 subjects with PD before and after 1 – 2 years of treatment and relate the findings to clinical features of disease progression. Finally we will compare concentrations of CNP products in 46 subjects developing intellectual impairment with an equal number showing mild or no impairment.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Because there is no established marker for the presence of PD, nor for the associated changes such as loss of higher mental function, accomplishing the above objectives would be a major advance for at least two reasons. First, it is possible that CNP measurements could be used as prognostic markers, and in monitoring or refining treatment and in planning management strategies. Second, showing that CNP products change as the disease progresses opens up the possibility that the peptide plays a role in the underlying mechanism causing loss of brain function. This may in turn lead to novel treatments restoring CNP production or the use of drugs mimicking its actions.
Anticipated Outcome:
The study will show whether measurements of CNP differ from normal in subjects with PD. It will also reveal whether changes in CNP are associated with any one or more of the several clinical syndromes observed during disease progression, and whether CNP products in CSF may be helpful in predicting intellectual decline.
Final Outcome
Using samples of cerebrospinal fluid (CSF) drawn from over 150 people with Parkinson’s disease we have found that the concentration of a product of C-type Natriuretic Peptide (CNP) gene expression (NTproCNP) is reduced compared to values found in people of similar age and without Parkinson’s. Although levels were unrelated to the duration, severity or clinical symptoms or signs, CSF levels were noted to fall further over time in subjects not receiving specific treatment. Moreover, lower levels at enrolment were associated with earlier requirement for starting treatment with levodopa. Of note, Deprenyl treatment- which delays the need for commencing levodopa prevented the decline in NTproCNP observed in subjects taking only a placebo. These findings suggest that CNP participates in the underlying chemistry associated with Parkinson’s and suggest that CNP may be neuroprotective and mediate some of the beneficial effects of drugs such as Deprenyl. Examining the potential benefit of CNP agonists in delaying disease progression would be a logical next step if these findings are confirmed in larger studies.