Encapsulated Cell Biodelivery of Nerve Growth Factor to the Basal Forebrain in Patients with Alzheimer’s Disease

Eriksdotter, Maria; Linderoth, Bengt; Lind, Göran; Aladellie, Layth; Almkvist, Ove; Andreasen, Niels; Blennow, Kaj; Bogdanović, Nenad; Jelić, Vesna; Kadir, Ahmadul; Nordberg, Agneta; Sundström, Erik; Wahlund, Lars‐Olof; Wall, Anders; Wiberg, Maria; Winblad, Bengt; Seiger, Åke; Almqvist, Per; Wahlberg, Lars U.

doi:10.1159/000336051

Cited by 135 publications

(89 citation statements)

References 85 publications

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“…These trials can be divided into the following 5 categories of surgical approaches: cerebrospinal fluid (CSF) shunting [4,5,6,7], intraventricular infusions [8,9,10,11,12,13,14,15,16], tissue grafting [17,18,19], gene therapy [20,21], and electrical neural stimulation [22,23,24,25,26] (table 1). The specific treatment strategies within each category are described in detail below (table 2).…”

Section: Methodsmentioning

confidence: 99%

“…Targeted gene therapy is an emerging therapeutic approach in neurosurgery for a range of neurological disorders, including brain tumors [44], PD [45,46] and AD [20,21]. A considerable amount of preclinical research shows that NGF stimulates cholinergic function, prevents the degeneration of cholinergic neurons and enhances memory [30,31,47].…”

Section: Published Human Trials Of Neurosurgical Treatments For Admentioning

confidence: 99%

“…Similar to the ex vivo genetic modification of autologous fibroblasts to produce NGF developed by Tuszynski et al [21], Eriksdotter-Jönhagen et al [20] and Wahlberg et al [52] have developed an encapsulated cell biodelivery technique using cells genetically modified to secrete NGF. The encapsulated cell biodelivery implant consists of a genetically modified NGF-secreting human cell line encapsulated behind a semipermeable hollow fiber membrane that allows the influx of nutrients and the efflux of NGF.…”

Section: Published Human Trials Of Neurosurgical Treatments For Admentioning

confidence: 99%

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The Neurosurgical Treatment of Alzheimer's Disease: A Review

Laxton

Stone

Lozano

2014

Stereotact Funct Neurosurg

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Background: Alzheimer's disease (AD) is a debilitating neurological illness of increasing prevalence. Because many patients are affected and current treatments have limited effectiveness, other therapeutic strategies are urgently needed. Objectives: Here we provide a review of the neurosurgical approaches that have been attempted or are currently being investigated for the treatment of AD. Methods: Computerized database searches identified all of the published studies in the English-language literature examining the surgical treatment of AD since 1950. Results: The following 5 categories of neurosurgical treatment were identified: cerebrospinal fluid shunting, intraventricular infusions, tissue grafting, gene therapy, and electrical neural stimulation. Conclusions: While none of the neurosurgical approaches applied to the treatment of AD have proven effective to date, recent trials involving gene therapy and electrical neural stimulation are showing promising early results. Larger trials investigating these treatments have been proposed or are currently under way.

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Section: Methodsmentioning

confidence: 99%

Section: Published Human Trials Of Neurosurgical Treatments For Admentioning

confidence: 99%

Section: Published Human Trials Of Neurosurgical Treatments For Admentioning

confidence: 99%

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The Neurosurgical Treatment of Alzheimer's Disease: A Review

Laxton

Stone

Lozano

2014

Stereotact Funct Neurosurg

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“…After 12 month observation, no adverse events were related to NGF or the device. Positive findings in cognition, EEG and nicotinic receptor binding in 2 of 6 patients were detected [4].…”

Section: Gene Therapymentioning

confidence: 95%

Application of Nerve Growth Factor in Alzheimer’s Disease

Long¹

2013

Clinic Pharmacol Biopharm

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Alzheimer's Disease (AD) is the most common form of dementia, which is characterized by a progressive decline in memory and cognitive function, accompanied with behavioral changes such as confusion, irritability and aggression, mood swings, language breakdown and eventually long-term memory loss. The most significant pathological findings in the brain affected by AD are senile plaques, neurofibrillary tangles, neuron loss or degeneration, particularly in the areas connected to the cerebral cortex and hippocampus, one of the most prominent among the regions being the basal forebrain cholinergic neurons. Although many basic and clinical studies have shown that drug treatment could improve the cognitive function and memory of AD patient, it is still a considerable challenge to delay and/or stop the neuron loss and degeneration.Previous studies showed that imbalance of neurotrophic factors in the brain and lack of neurotrophic support causes neuronal atrophy and death. Among the neurotrophic factors, Nerve Growth Factor (NGF) is the best characterized one. Knockout of NGF in adult transgenic mice leads to severe neuronal death in basal forebrain cholinergic neurons. Several in vivo and in vitro studies have demonstrated that Intra Cerebro Ventricular (ICV) NGF administration completely prevents the retrograde degeneration of cholinergic neurons and increases learning and memory in the animal model of AD [1]. However, NGF is a large molecular protein that does not easily cross the blood-brain barrier. The delivery of NGF to the brain poses a major challenge for clinical application. Here, we will focus on the delivery strategies of NGF on brain and beneficial effects of delivered NGF on cholinergic neurons and functional recovery of AD. ICV NGF AdministrationThe beneficial effects of ICV NGF administration in the AD model with fimbria-fornix transection have been studies nearly 30 years ago. Studies performed in aged animals showed that ICV NGF administration could reverse age-associated basal forebrain cholinergic neuronal degeneration and improve the learning and memory. Furthermore, in non-human primate brain, the ability of NGF could also prevent basal forebrain cholinergic neuronal degeneration and correct the learning and memory. One clinical trial was reported in 1998. In this study, three AD patients were treated with murine ICV NGF injection and showed certain beneficial effects. Two negative side effects occurred after NGF treatment, back pain and weight reduction [2]. Scientists keep seeking options to deliver NGF into the brain.

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“…So far, encapsulation has been used primarily to treat T1DM [5][6][7][8][9]. By providing a physical barrier to immune rejection, islet encapsulation has been shown to allow transplanted islet to function normally and avoid the use of immunosuppression [10,11].…”

Section: Introductionmentioning

confidence: 99%

Avoiding Immunosuppression for Islet Transplantation: Use of Protective Biomaterials

Alexander¹,

Nguyen²,

Flores³

et al. 2017

Challenges in Pancreatic Pathology

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Islet transplantation, with the advent of the Edmonton protocol in 2000, has offered a significant alternative for long-lasting treatment of type 1 diabetes. However, the immunosuppression required for transplantation has the cytotoxic effect on pancreatic islets, and thus limiting the long-term efficacy of the transplant. Immediate loss of islets after transplant was also observed because of immediate blood-mediated inflammatory response (IBMIR), which kills islets transplanted in the liver through portal vein. There is also commonly a lack of microvascular blood supply to the transplanted islets. In this chapter, we will review the variety of technologies used to protect transplanted islets against toxicity of immunosuppression, immune rejection, and inflammatory response. We will evaluate the mechanisms of these technologies and their progress in solving the challenges to islet transplantation. The technologies include encapsulation of transplanted islets in various polymers, transplants in sites other than the liver, and creation of new prevascularized transplant site. These technologies offer several mechanisms to prevent immune rejection or immediate contact with cytotoxic inflammatory response, in addition to maintaining islet integrity. New transplant sites are also being developed to support the islets, by allowing establishment of microvasculature and innervation, prior to addition of the islets.

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Encapsulated Cell Biodelivery of Nerve Growth Factor to the Basal Forebrain in Patients with Alzheimer’s Disease

Cited by 135 publications

References 85 publications

The Neurosurgical Treatment of Alzheimer's Disease: A Review

The Neurosurgical Treatment of Alzheimer's Disease: A Review

Application of Nerve Growth Factor in Alzheimer’s Disease

Avoiding Immunosuppression for Islet Transplantation: Use of Protective Biomaterials

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