PROJECT SUMMARY/ABSTRACT
Cognitive decline in the spectrum of Alzheimer’s disease (AD) including Dementia with Lewy Bodies (DLB) and
Parkinson’s disease with dementia (PDD) takes a severe toll on patients, family, and society in suffering and
cost. The memory and cognitive deficits observed in AD, DLB and PDD are attributable in large part to a loss of
cholinergic function and neurons in the brain, especially but not limited to cells in the nucleus basalis of Meynert
(NBM). The greatest unmet need for AD, DLB and PDD are therapies that can go beyond symptom treatment to
possibly stabilize or maintain cholinergic circuits. As part of clinical trials, we have been delivering mixed-cell,
pro-regenerative peripheral nerve tissue (PNT) to areas of the brain affected in neurodegenerative disease. Here
we propose a Phase I single surgical-center, double-blinded clinical trial involving bilateral autologous PNT into
the NBM to address “repair cell” support of cholinergic neurons. The major goal of this trial is to identify the
feasibility and safety of bilateral implantation of reparative PNT to the NBM with the eventual goal to improve
function of cholinergic neurons in dementias. Twenty-four participants, diagnosed with PD and who have
selected, qualified, and agreed to undergo DBS surgery of the globus pallidus internus (GPi), will be followed for
24 months as part of a trial to receive, at the time of DBS surgery, PNT implanted bilaterally into the NBM (twelve
participants) or an alternate target also affecting cognition in this population, the substantia nigra (SN). DBS will
be implanted and programmed to provide the standard of care. Feasibility objectives will be based on the number
of participants receiving PNT delivery and the number of participants completing the 12- month and 24-month
study visits. For the safety objective, the number of serious adverse events related to the procedure will be
collected for 24 months following surgery. Cognitive safety endpoints at 12 and 24-months following surgery will
be defined as ≥ 1.5 standard deviation decrement relative to the participant’s estimated pre-morbid functioning.
To aid in future trial designs, secondary outcome analyses will use neuropsychological testing of subjects (at 12
and 24-months after surgery compared to baseline) and Movement Disorder Society – Unified Parkinson’s
Disease Rating Scale (MDS-UPDRS) evaluations and quality of life assessments at 6, 12 and 24-months after
surgery compared to baseline. We will continue to expand our brain bank activities in conjunction with the
University of Colorado Anschutz Medical Campus to assess the histological effects of the investigational cell
therapy in participants who have donated their brain after death and to better characterize the disease process
in our study subjects. This study is a critical step for identifying the feasibility of this NBM vs. SN design for trialing
in subsequent multicenter, Phase II studies and for continuing to move this approach forward as an eventual
monotherapy for the treatment of the Spectrum of AD.