Using Heavy Water to Study Cell Dynamics in Parkinson's Disease

This pilot study will assess the feasibility of using heavy water as a safe 'tracer' for
biomarker studies of diseases of the brain and spinal cord, that, together, are also called
the central nervous system (CNS). Heavy water, also called deuterated water or D20, is the
same as normal drinking water except the hydrogen atoms have been replaced by deuterium, a
naturally occurring isotope of hydrogen. In particular, this study will use heavy water to
define: 1) The rate of immune cell proliferation (growth) in the cerebrospinal fluid (CSF)
compared to blood. This study will be examining a particular type of immune cell called T
lymphocytes. 2) This study will also examine selected molecules generated by nerve cells of
the CNS to understand their rate of secretion and turnover in healthy control participants,
HIV-1-infected participants and participants with a non-HIV-related neurodegenerative
disease such as Parkinson's disease (PD).

This study will involve the administration of heavy water orally for either seven days, 12
days or six weeks. Measurements will be taken by lumbar puncture (LP, also known as a
spinal tap). Blood (approximately five tablespoons per visit) will also be obtained at each
of the lumbar puncture appointments.

If this method can be used to establish the rates of immune cell turnover and the production
rates of neuronal molecules using cerebrospinal fluid, it will provide unique data that is
important to understand chronic neurodegenerative conditions, like PD, and to measure
responses to targeted therapies.

Hypothesis:

1. D2O, administered orally, can be used to measure the proliferation rates of CSF T cells
(and, eventually, of their major phenotypic subsets).

2. D2O can be used to assess the turnover and production rates of CNS constituents that
are normally or pathologically shed or secreted into the CSF, including (eventually):
cargo molecules transported specifically in neurons in the CNS, such as chromogranin-A
and -B, neuregulin-1 (specifically the extracellular secreted ectodomain of neuronal
differentiation factor (NDF) isoform type α1, α2, β1, and the acetylcholine receptor
inducing activity isoform (ARIA), secreted amyloid precursor protein (sAPP),
alpha-synuclein; and APP metabolites amyloid beta (Aβ) 41 and 42.