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World Stem Cell Summit 2010

Monday, May 12, 2008

2 Stem Cell Patents Issued Last Week

 

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Dear manoj kumar valluru,

Last week 2 patents of relevance to the area of stem cells were issued.

  1. # 7,368,115 (Patent Spotlight), Canadian company Stem Cell Therapeutics (TSX-V:SSS) gets issued a patent on using the peptide PACAP for activating stem cells in vivo and in vitro.
  2. # 7,368,279 discloses a method of making artificial sphincters.

 


Method of enhancing neural stem cell proliferation, differentiation, and survival using pituitary adenylate cyclase activating polypeptide (PACAP)
 
 
Patent Number: 7,368,115

Pharmaceutical activation of stem cells is arguably the next major revolution in medicine. The current patent is assigned to a Canadian stem cell company, Stem Cell Therapeutics (TSX-V:SSS), which already has entered Phase II clinical trials with pharmaceutical activators of endogenous stem cells for the treatment of stroke. While the ongoing clinical work of Stem Cell Therapeutics involves administration of erythropoietin and human chorionic gonadotrophin for activation of endogenous neural stem cells, the current patent covers the use of a peptide hormone for a similar purpose.

The hormone covered is pituitary adenylate cyclase-activating polypeptide (PACAP), a neurotransmitter involved in control of metabolism, neurological function, and development. PACAP belongs to a superfamily of nine structurally related hormones that also share anatomical distribution (brain and gut), function (activation of cAMP), and receptors (seven-transmembrane receptor). The hormones belonging to this superfamily include glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, glucose-dependent insulinotropic polypeptide (GIP), GH-releasing hormone (GRF), peptide histidine-methionine (PHM), PACAP, secretin, and vasoactive intestinal polypeptide (VIP). The reason we mention these similarities is because GLP receptor activators have previously been shown to induce activation of endogenous pancreatic stem cells.

A brief understanding of the current patent can be seen by reading the first issued claim "A method for increasing neural stem cell and/or neural stem cell progeny number comprising: adding pituitary adenylate cyclase-activating polypeptide (PACAP) to multipotent neural stem cells in an amount effective to increase neural stem cell and/or neural stem cell progeny number, said method further comprising adding prolactin." This issued claim is very potent, it is not restricted to in vitro or in vivo.

The dependent claims cover not only stimulation of proliferation but also inhibition of neural stem cell apoptosis. Stem cell activation/protection includes both exogenous stem cells, as well as endogenous stem cells, such as those from the subventricular zone. The use of PACAP together with prolactin is also covered for treatment of neurodegenerative diseases, stroke, Parkinson's, Alzheimer's, and Huntington's. Combinations of PACAP with other agents such as FGF-2, heparan sulphates, and EGF are also covered.

In the examples section of the specification, in vitro stimulation of neurospheres, as well as in vivo induction of subventricular zone neurons is provided. Interestingly, an independent group (Wang et al. Neuroprotective effects of PACAP27 in mice model of Parkinson's disease involved in the modulation of K(ATP) subunits and D2 receptors in the striatum. Neuropeptides. 2008 Apr 25) has published that administration of PACAP has a therapeutic effect on an animal model of Parkinson's.

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  Immunology Instead of Stem Cells: Vaccine for Alzheimer's

Sunday May 11th, 2008 @ 17:30:29 EST

Huntington Beach, CA -

A recent paper from Dr. Agadjanyan's group at the Institute of Molecular Medicine (Movsesyan et al. Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine - a novel immunotherapeutic strategy. PLoS ONE 2008 May 7;3(5):e2124) reports the successful treatment of a mouse model of Alzheimer's using DNA vaccination against amyloid protein peptides. 

Previously clinical trials were conducted using vaccination towards amyloid protein.  Efficacy was associated with antibody responses.  Autoreactivity induced by cytotoxic lymphocytes was a cause of potential safety concerns.  Although microglial activation is associated with reduction in plaque size in some models (Herber et al. Microglial activation is required for Abeta clearance after intracranial injection of lipopolysaccharide in APP transgenic mice. J Neuroimmune Pharmacol. 2007 Jun;2(2):222-31) , it appears that the main therapeutic effect of amyloid derived peptide vaccination is associated with humoral immunity.

In order to stimulate a specific humoral response, the authors generated a DNA vaccine that contained 3 identical peptides that are B cell epitopes of the amyloid beta protein (1-11), a strong T helper epitope, and a "molecular adjuvant" that acts as a Th2 chemoattractant (CCL22). 

Administration of this DNA vaccine to the triple transgenic Alzheimer's mouse model induced a potent Th2 response and high levels of antibodies to Abeta.  Importantly, the vaccine prevented behavioural abnormalities, as well as pathological score associated with disease onset.  No adverse effects were observed associated with this vaccination. 

This important study poses a method of prophylactically using the immune system to prevent a neurodegenerative disorder.  Given that recent studies in similar Alzheimer's Disease models have demonstrated a role for endogenous hippocampal stem cells (Ermini et al. Neurogenesis and Alterations of Neural Stem Cells in Mouse Models of Cerebral Amyloidosis. Am J Pathol. 2008 May 8), it will be interesting to see how such immune modulatory approaches may be used together with stem cell therapy. 

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  RECENTLY ADDED PATENTS  
  Three dimensional bioengineered smooth muscle tissue and sphincters and methods therefor (7,368,279)
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  Method of enhancing neural stem cell proliferation, differentiation, and survival using pituitary adenylate cyclase activating polypeptide (PACAP) (7,368,115)
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  Multi-lineage directed induction of bone marrow stromal cell differentiation (7,364,900)
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  Loop peptide and TGF.alpha. for stimulating stem cell proliferation and migration (7,365,172)
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  Methods of cancer therapy targeted against a cancer stem line (7,361,336)
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  Multipotent neural stem cell compositions (7,361,505)
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  Differentiation of specialized dermal and epidermal cells into neuronal cells (7,361,506)
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  Placental growth factor as a target for the treatment of osteoporosis (7,357,929)
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  Device and method for culturing cells (7,358,082)
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  Method for rapid generation of mature dendritic cells (7,354,909)
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