Model Systems and Treatment Regimes for Treatment of Neurological Disease
AssigneeNoNO Inc.
InventorsMichael Tymianski, Jonathan David Garman
Life of this patent
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Abstract
The invention provides animal models and clinical trials for assessing agents for potential use in treating and effecting prophylaxis stroke and other neurological diseases, particularly those mediated at least in part by excitoxitity. The invention also provides preferred dosage and infusion regimes and pharmaceutical compositions for clinical application of such agents.
Claims48
A method of treating or effecting prophylaxis of disease mediated by excitotoxicity, comprising administering to a subject having or at risk of the disease a pharmacological agent that inhibits binding of PSD-95 to NMDAR 2B and/or of PSD-95 to nNOS, wherein when the agent is a peptide having the amino acid sequence YGRKKRRQRRRKLSSIESDV (SEQ ID NO:6), the dose is 2-3 mg/kg, and if the agent is other than the peptide having the amino acid sequence YGRKKRRQRRRKLSSIESDV, the dose delivers the equivalent effective concentration of the agent to 2-3 mg/kg of the peptide having the amino acid sequence YGRKKRRQRRRKLSSTESDV.
A method of treating or effecting prophylaxis of a disease mediated by excitotoxicity, comprising administering to a subject having or at risk of the disease a pharmacological agent that inhibits binding of PSD-95 to NMDAR 2B and/or PSD-95 to nNOS, wherein the agent is linked to an internalization peptide, and the agent is administered by intravenous infusion over a period of 5-15 minutes.
A method of inhibiting ischemic damage from neurosurgery or endovascular surgery to a blood vessel connecting the brain to the heart or supplying blood to a limb, kidney, retina or spinal cord comprising administering an effective regime of an agent that inhibits binding of PSD-95 to NMDAR 2B to a subject undergoing the neurosurgery or endovascular surgery to a blood vessel.
A method of performing a clinical trial on a pharmacological agent comprising administering the pharmacological agent to a population of subjects undergoing endovascular surgery on a blood vessel in the brain or connecting the brain to the heart or supplying blood to a limb, retina, kidney or spinal cord;
- and comparing the frequency of a damaging effect of the surgery in the subjects compared with control subjects undergoing the endovascular surgery without the pharmacological agent, to determine whether the pharmacological agent reduces the damaging effect.
A method of testing a pharmacological agent comprising, comprising
- a. inserting particles into a cerebral blood vessel of a primate;
- b. administering the pharmacological agent to the primate
- c. comparing a damaging effect of step (a) in the primate compared to a control primate not treated with the compound.
A lyophilized composition comprising the peptide having the amino acid sequence YGRKKRRQRRRKLSSIESDV (SEQ ID NO:6) lyophilized from a solution of the peptide in normal saline prepared under GMP conditions.
A method of storing a pharmaceutical composition comprising
- storing a pharmaceutical composition comprising a peptide having the amino acid sequence YGRKKRRQRRRKLSSIESDV (SEQ ID NO:6) at concentration of 10-30 mg/ml in normal saline under GMP conditions at below 0° C. for a period of at least two years.
Dependencies are inferred from the claim text.