The Hospital for Sick Children

Nono Inc.

UniversitÈ Laval

Arbor Vita Corporation

Michael W Salter

Michael Tymianski

Jonathan David Garman

Peter S Lu

Michael P Belmares

Jeffrey R Gingrich

Yves De Koninck

Jeffrey A M Coull

Hans-Michael Dosch

Simon Beggs

Lan Tang

Yin Chan

J David Garman

The invention provides agents useful for treating pain. An exemplary agent comprises or consists of the a portion of a retroviral Tat protein. One such agent is the peptide Tat-NR2B9c. This peptide has previously been described as an agent for inhibiting damaging effects of stroke and similar conditions via inhibition of PSD95 interactions with NMDA receptors and/or NOS. The present application provides data showing that the Tat-NR2B9c peptides is effective in alleviation of pain. The alleviation of pain can be obtained at a dose of the peptide below the dose required to inhibit PSD-95 interactions with NMDAR or NOS.

Methods for treating pain

The invention provides methods for treating stroke and compositions for use in the same. The methods employ a chimeric peptide of an active peptide and an internalization peptide. The internalization peptide is a tat variant that promotes uptake of itself and a linked active peptide into a cell without substantial binding to N-type calcium channels. Use of the tat variant allows treating of stroke free of certain side effects associated with binding to N-type calcium channels. Tat variant peptides can also be linked to other active agent for use in treating other diseases.

Treating stroke and other diseases without inhibiting N-type calcium channels

The present invention provides a method for ameliorating inflammatory and/or neuropathic pain in a subject by modifying the activity of N-methyl-D-aspartate (NMDA) receptors in cells of the subject by inhibition of the interaction of the unique domain of the tyrosine kinase Src enzyme and the NMDA receptor complex.

Method for ameliorating pain by modification of NMDA receptors through inhibition of SRC

Methods and products for the attenuation or treatment of pain and the reduction of nociception are described. The methods and products are based on the modulation of neuroglia-derived BDNF expression or activity. Also described herein are commercial packages and uses based on such modulation. Related methods for identifying or characterizing compounds for the treatment of pain and the reduction of nociception are also described.

Modulation of neuroglia-derived BDNF in the treatment and prevention of pain

Method for ameliorating pain by modification of NMDA receptors through inhibition of Src

A process is disclosed for controlling inflammatory tissue access through release of neuropeptides, such as substance P (sP), to insulin-responsive sensory neurons, whereby simultaneous control of insulin sensitivity/resistance is manifested. In models of Type 1 and Type 2 diabetes, sensory afferents, in particular TRPV1, have fundamental roles in insulin/glucose homeostasis, islet physiology and autoimmune tissue inflammation. By manipulation of the TRPV1 neuro-&#x3b2;-cell circuit or enhancement of pancreatic sP levels, normalization of insulin resistance, clearance of inflammation and prevention of both Type 1 and Type 2 diabetes is realized.

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The present invention provides a method for modifying the activity of NMDA (N-methyl-D-aspartate)receptors in cells by inhibition of the interaction of the unique domain of the tyrosine kinase Src enzyme and the NMDA receptor complex.

Method for modification of NMDA receptors through inhibition of Src

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Toronto, Canada

Michael W Salter