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Patent
Neurodyn | Date: 2016-09-02

The invention relates to methods and compositions for treating a neurodegenerative disease. More particularly, the present invention is directed to methods of treatment of neurodegenerative diseases using progranulin and progranulin polypeptides, and methods of treatment of neurodegenerative diseases using effectors, or combinations of effectors, that modify progranulin expression.


Chitramuthu B.P.,McGill University | Chitramuthu B.P.,Neurodyn | Baranowski D.C.,Neurodyn | Kay D.G.,Neurodyn | And 2 more authors.
Molecular Neurodegeneration | Year: 2010

Background. Progranulin (PGRN) encoded by the GRN gene, is a secreted glycoprotein growth factor that has been implicated in many physiological and pathophysiological processes. PGRN haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to progressive neuronal atrophy in the form of frontotemporal lobar degeneration (FTLD). This form of the disease is associated with neuronal inclusions that bear the ubiquitinated TAR DNA Binding Protein-43 (TDP-43) molecular signature (FTLD-U). The neurotrophic properties of PGRN in vitro have recently been reported but the role of PGRN in neurons is not well understood. Here we document the neuronal expression and functions of PGRN in spinal cord motoneuron (MN) maturation and branching in vivo using zebrafish, a well established model of vertebrate embryonic development. Results. Whole-mount in situ hybridization and immunohistochemical analyses of zebrafish embryos revealed that zfPGRN-A is expressed within the peripheral and central nervous systems including the caudal primary (CaP) MNs within the spinal cord. Knockdown of zfPGRN-A mRNA translation mediated by antisense morpholino oligonucleotides disrupted normal CaP MN development resulting in both truncated MNs and inappropriate early branching. Ectopic over-expression of zfPGRN-A mRNA resulted in increased MN branching and rescued the truncation defects brought about by knockdown of zfPGRN-A expression. The ability of PGRN to interact with established MN developmental pathways was tested. PGRN over-expression was found to reverse the truncation defect resulting from knockdown of Survival of motor neuron 1 (smn1). This is involved in small ribonucleoprotein biogenesis RNA processing, mutations of which cause Spinal Muscular Atrophy (SMA) in humans. It did not reverse the MN defects caused by interfering with the neuronal guidance pathway by knockdown of expression of NRP-1, a semaphorin co-receptor. Conclusions. Expression of PGRN within MNs and the observed phenotypes resulting from mRNA knockdown and over-expression are consistent with a role in the regulation of spinal cord MN development and branching. This study presents the first in vivo demonstration of the neurotrophic properties of PGRN and suggests possible future therapeutic applications in the treatment of neurodegenerative diseases. © 2010 Chitramuthu et al; licensee BioMed Central Ltd.


Van Kampen J.M.,Neurodyn | Van Kampen J.M.,University of Prince Edward Island | Baranowski D.B.,Neurodyn | Shaw C.A.,University of British Columbia | And 2 more authors.
Experimental Gerontology | Year: 2014

Panax ginseng has been used in traditional Chinese medicine for centuries. Among its various benefits is a pluripotent targeting of the various events involved in neuronal cell death. This includes anti-inflammatory, anti-oxidant, and anti-apoptotic effects. Indeed, ginseng extract and its individual ginsenosides have been demonstrated to influence a number of biochemical markers implicated in Parkinson's disease (PD) pathogenesis. We have reported previously that administration of the ginseng extract, G115, afforded robust neuroprotection in two rodent models of PD. However, these traditional rodent models are acute in nature and do accurately recapitulate the progressive nature of the disease. Chronic exposure to the dietary phytosterol glucoside, β-sitosterol β. d-glucoside (BSSG) triggers the progressive development of neurological deficits, with behavioral and cellular features that closely approximate those observed in PD patients. Clinical signs and histopathology continue to develop for several months following cessation of exposure to the neurotoxic insult. Here, we utilized this model to further characterize the neuroprotective effects of the ginseng extract, G115. Oral administration of this extract significantly reduced dopaminergic cell loss, microgliosis, and accumulation of α-synuclein aggregates. Further, G115 administration fully prevented the development of locomotor deficits, in the form of reduced locomotor activity and coordination. These results suggest that ginseng extract may be a potential neuroprotective therapy for the treatment of PD. © 2013 Elsevier Inc.


Van Kampen J.M.,Neurodyn | Van Kampen J.M.,University of Prince Edward Island | Baranowski D.,Neurodyn | Kay D.G.,Neurodyn | Kay D.G.,University of Prince Edward Island
PLoS ONE | Year: 2014

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by tremor, rigidity and akinesia/bradykinesia resulting from the progressive loss of nigrostriatal dopaminergic neurons. To date, only symptomatic treatment is available for PD patients, with no effective means of slowing or stopping the progression of the disease. Progranulin (PGRN) is a 593 amino acid multifunction protein that is widely distributed throughout the CNS, localized primarily in neurons and microglia. PGRN has been demonstrated to be a potent regulator of neuroinflammation and also acts as an autocrine neurotrophic factor, important for long-term neuronal survival. Thus, enhancing PGRN expression may strengthen the cells resistance to disease. In the present study, we have used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD to investigate the possible use of PGRN gene delivery as a therapy for the prevention or treatment of PD. Viral vector delivery of the PGRN gene was an effective means of elevating PGRN expression in nigrostriatal neurons. When PGRN expression was elevated in the SNC, nigrostriatal neurons were protected from MPTP toxicity in mice, along with a preservation of striatal dopamine content and turnover. Further, protection of nigrostriatal neurons by PGRN gene therapy was accompanied by reductions in markers of MPTP-induced inflammation and apoptosis as well as a complete preservation of locomotor function. We conclude that PGRN gene therapy may have beneficial effects in the treatment of PD. © 2014 Van Kampen et al.


The invention relates to methods and compositions for treating a neurodegenerative disease. More particularly, the present invention is directed to methods of treatment of neurodegenerative diseases using progranulin and progranulin polypeptides, and methods of treatment of neurodegenerative diseases using effectors, or combinations of effectors, that modify progranulin expression.


The disclosure relates to selected administration routes for CNS (central nervous system) therapeutics and highly soluble salts, solutions, emulsions or powder formulations thereof, having optimal brain delivery due to the mode of administration and the chemical nature of the compounds of the disclosure.


Patent
Neurodyn | Date: 2012-03-30

The invention relates to the identification of sterol glucoside toxins, and provides methods for detecting and detoxifying the compounds, as well as therapeutic methods for treating subjects exposed to such toxins. In alternative embodiments, the toxins may for example include beta-sitostrol-beta-D-glucoside (5-cholesten-24b-ethyl-3b-ol-D-glucoside) or cholesterol glucoside (5-cholesten-3b-ol-3b-D-glucoside).


Trademark
Neurodyn | Date: 2016-09-20

Dietary supplements; natural health products, namely, dietary supplements; nutritional supplements; herbal supplements; medicinal herbal preparations; medicinal herbal extracts for medical purposes; vitamin and mineral supplements. Wholesale distributorships featuring dietary supplements, natural health products, nutritional supplements, herbal supplements, medicinal herbal preparations, medicinal herbal extracts for medical purposes, vitamin and mineral supplements; Online retail stores services featuring dietary supplements, natural health products, nutritional supplements, herbal supplements, medicinal herbal preparations, medicinal herbal extracts for medical purposes, vitamin and mineral supplements; Retail store services featuring dietary supplements, natural health products, nutritional supplements, herbal supplements, medicinal herbal preparations, medicinal herbal extracts for medical purposes, vitamin and mineral supplements; Retail services by direct solicitation by sales agents in the field of dietary supplements, natural health products, nutritional supplements, herbal supplements, medicinal herbal preparations, medicinal herbal extracts for medical purposes, vitamin and mineral supplements. Consulting services in the field of nutrition of dietary supplements, natural health products, nutritional supplements, herbal supplements, medicinal herbal preparations, medicinal herbal extracts for medical purposes, and vitamin and mineral supplements.


Trademark
Neurodyn | Date: 2013-03-11

Herbal supplements containing ginseng and ginsenocides, in tablet, capsule, gel, powder or liquid form, for both the prevention and treatment of neurodegenerative diseases, namely, Parkinsons disease, Alzheimers disease, and Amyotrophic lateral sclerosis, and the treatment of spinal cord injury, brain injury, promotion and maintenance of healthy neurons, memory, and cognitive function; Nutritional supplements containing ginseng, in tablet, capsule, gel, powder or liquid form, for both the prevention and treatment of neurodegenerative diseases, namely, Parkinsons disease, Alzheimers disease, and Amyotrophic lateral sclerosis, and the treatment of spinal cord injury, brain injury, promotion and maintenance of healthy neurons, memory, and cognitive function; Nutritional supplements containing ginseng and omega-3 fatty acids, in tablet, capsule, gel, powder or liquid form, for both the prevention and treatment of neurodegenerative diseases, namely, Parkinsons disease, Alzheimers disease, and Amyotrophic lateral sclerosis, and the treatment of spinal cord injury, brain injury, promotion and maintenance of healthy neurons, memory, and cognitive function; Nutritional supplements containing ginsenocides, in tablet, capsule, gel, powder or liquid form, for both the prevention and treatment of neurodegenerative diseases, namely, Parkinsons disease, Alzheimers disease, and Amyotrophic lateral sclerosis, and the treatment of spinal cord injury, brain injury, promotion and maintenance of healthy neurons, memory, and cognitive function; Nutritional supplements containing ginsenocides and omega-3 fatty acids, in tablet, capsule, gel, powder or liquid form, for both the prevention and treatment of neurodegenerative diseases, namely, Parkinsons disease, Alzheimers disease, and Amyotrophic lateral sclerosis, and the treatment of spinal cord injury, brain injury, promotion and maintenance of healthy neurons, memory, and cognitive function; Nutritional supplements containing ginseng extract, in tablet, capsule, gel, powder or liquid form, for both the prevention and treatment of neurodegenerative diseases, namely, Parkinsons disease, Alzheimers disease, and Amyotrophic lateral sclerosis, and the treatment of spinal cord injury, brain injury, promotion and maintenance of healthy neurons, memory, and cognitive function; Nutritional supplements containing ginseng extract and omega-3 fatty acids, in tablet, capsule, gel, powder or liquid form, for both the prevention and treatment of neurodegenerative diseases, namely, Parkinsons disease, Alzheimers disease, and Amyotrophic lateral sclerosis, and the treatment of spinal cord injury, brain injury, promotion and maintenance of healthy neurons, memory, and cognitive function; medical foods supplements in powdered, liquid and tablet form for the prevention and treatment of neurodegenerative disease, Alzheimers disease, Parkinsons disease, and Amyotrophic lateral sclerosis; medical food for the treatment of spinal cord injury and brain injury; medical food supplements in powdered, liquid and tablet form; medical food supplements in powdered, liquid and tablet form for use in the dietary management of patients with neurodegenerative diseases, Alzheimers disease, Parkinsons disease, Amyotrophic lateral sclerosis, spinal cord injury, and brain injury; ginseng, ginsenocides and omega-3 fatty acids for the dietary management of neurodegenerative disease, Alzheimers disease, Parkinsons disease, Amyotrophic lateral sclerosis, spinal cord injury, and brain injury.


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