Nerve growth factor affects11C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient (Case Report)

Abstract

Based on animal research suggesting that nerve growth factor (NGF) can stimulate central cholinergic neurons, the known losses of cholinergic innervation of the cortices in Alzheimer's disease (AD), and our experience of infusing NGF to support adrenal grafts in parkinsonian patients, we have initiated clinical trials of NGF infusions into the brain of patients with AD. Here we report a follow-up of our first case, a 69-year-old woman, with symptoms of dementia since 8 years. Intraventricular infusion of 6.6 mg NGF during three months resulted in a marked transient increase in uptake and binding of 11C-nicotine in frontal and temporal cortex and a persistent increase in cortical blood flow as measured by PET as well as progressive decreases of slow wave EEG activity. After one month of NGF, tests of verbal episodic memory were improved whereas other cognitive tests were not. No adverse effects could be ascribed to the NGF infusion. Taken together, the results of this case study indicate that NGF may counteract cholinergic deficits in AD, and suggest that further clinical trials of NGF infusion in AD are warranted.

Systemic Administration of a Nerve Growth Factor Conjugate Reverses Age-Related Cognitive Dysfunction and Prevents Cholinergic Neuron Atrophy

“…In such studies performed to date, positive changes in cerebral blood flow, EEG power spectrum, and nicotinic cholinergic receptor density were observed in two patients receiving NGF directly into the lateral ventricle through a cannula (Olson et al, 1992). Unfortunately, peripherally administered NGF does not pass through the blood-brain barrier (BBB) in physiologically relevant amounts (Kordower et al, 1993;Loy et al, 1994), so that treatment with NGF in SDAT patients has thus far required intracranial surgery.…”

Neuroprotection in experimental stroke with targeted neurotrophins

“…18 Encouraged by these preclinical results, a female Alzheimer patient received NGF treatment in 1991. 19 This represented the first case of clinical trial with neurotrophin. Knowing the poor BBB penetration of NGF after peripheral administration, the patient received NGF via a slow intracerebroventricular infusion for a period of 3 months!…”

Cerebrospinal fluid and blood biomarkers in Alzheimer’s disease

“…The growth factor NGF is the most potent factor in counteracting cholinergic cell death [110] . Growth factors have been considered as possible treatments for AD [110] . However, results from plasma growth factor levels have been conflicting.…”