Abstract: Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease affecting at least 400,000 individuals in the United States and 2.3 million persons worldwide. Its counterpart in the peripheral nervous system, chronic Inflammatory demyelinating polyradiculoneuropathy (CIPD), affects approximately 40,000 patients In the United States. Both diseases have a relatively young age at diagnosis and require lifelong therapy to slow progression. These two diseases both result from the immune system attacking the integrity of the myelin sheath, the protective coating of neurons. The therapies common to these two diseases are corticosteroids, and plasma exchange/IVIG therapy for the treatment of symptoms, and they are generally immunosuppressive. Hence, there is a need to develop a therapy that would selectively inhibit the specific pathological entities like autoantibodies that bind to the myelin sheath.

Abstract: This invention is in the field of medicinal pharmacology. In particular, the present invention relates to pharmaceutical agents which function as inhibitors of TDP-43 activity. The invention further relates to methods of treating and/or ameliorating symptoms related to conditions associated with TDP-43 activity (e.g., neurodevelopmental disorders), comprising administering to a subject (e.g., a human patient) a composition comprising one or more pharmaceutical agents which function as inhibitors of TDP-43 activity.

Abstract: This invention relates generally to neurodegenerative diseases and conditions (e.g., Alzheimer's disease) characterized with aberrant RIPK1/RIPK3 binding, RIPK3/MLKL binding, necrosome formation, and/or necroptosis activation. This invention further relates to methods and compositions for treating such neurodegenerative diseases and conditions with pharmaceutical compositions comprising agents capable of inhibiting RIPK1/RIPK3 binding and/or RIPK3/MLKL binding.

Abstract: This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a piperidinyl-benzoimidazole structure which function as antagonists of small ubiquitin like modifier (SUMO) related modification (SUMOylation) of collapsin response mediator protein 2 (CRMP2), and their use as therapeutics for the treatment of voltage gated sodium channel 1.7 (Nav1.7) related itch, anosmia, migraine event, and/or pain (e.g., neuropathic pain).

Abstract: The present invention provides compounds that can modulate the amount of Nav1.7 protein, a key protein in pain signaling, that is present in the cellular surface and methods for using such compounds. In particular, compounds of the invention modulate the amount of Nav1.7 protein on the cellular surface by modulating SUMOylation of CRMP2. Thus, compounds of the invention can be used to treat various clinical conditions associated with the presence and/or activation of Nav1.7 protein on the cellular surface and/or SUMOylation of CRMP2.

Abstract: This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a piperidinyl-benzoimidazole structure which function as antagonists of small ubiquitin like modifier (SUMO) related modification (SUMOylation) of collapsin response mediator protein 2 (CRMP2), and their use as therapeutics for the treatment of voltage gated sodium channel 1.7 (Nav1.7) related itch, anosmia, migraine event, and/or pain (e.g., neuropathic pain).

Abstract: The present invention provides compounds that can modulate the amount of Nav1.7 protein, a key protein in pain signaling, that is present in the cellular surface and methods for using such compounds. In particular, compounds of the invention modulate the amount of Nav1.7 protein on the cellular surface by modulating SUMOylation of CRMP2. Thus, compounds of the invention can be used to treat various clinical conditions associated with the presence and/or activation of Nav1.7 protein on the cellular surface and/or SUMOylation of CRMP2.

Abstract: The present invention provides compounds that can modulate the amount of Nav 1.7 protein, a key protein in pain signaling, that is present in the cellular surface and methods for using such compounds. In particular, compounds of the invention modulate the amount of Nav 1.7 protein on the cellular surface by modulating SUMOylation of CRMP2. Thus, compounds of the invention can be used to treat various clinical conditions associated with the presence and/or activation of Nav 1.7 protein on the cellular surface and/or SUMOylation of CRMP2.

Abstract: Disclosed herein are isolated polypeptides capable of preventing collapsin response mediator protein 2 (CRMP2)-small ubiquitin-like modifier (SUMO)ylation mediated trafficking of voltage gated sodium channel 1.7 (Nav1.7) function. In some examples, the disclosed peptides comprise three to twenty amino acids and include the amino acid sequence KMD. Also disclosed are methods of decreasing nociception including administering an effective amount of one or more disclosed peptides to a subject in need thereof, such as a subject experiencing chronic pain.

Abstract: The present invention provides compounds that can modulate the amount of Nav 1.7 protein, a key protein in pain signaling, that is present in the cellular surface and methods for using such compounds. In particular, compounds of the invention modulate the amount of Nav 1.7 protein on the cellular surface by modulating SUMOylation of CRMP2. Thus, compounds of the invention can be used to treat various clinical conditions associated with the presence and/or activation of Nav 1.7 protein on the cellular surface and/or SUMOylation of CRMP2.

Abstract: Disclosed herein are isolated polypeptides capable of preventing collapsin response mediator protein 2 (CRMP2)-small ubiquitin-like modifier (SUMO)ylation mediated trafficking of voltage gated sodium channel 1.7 (Nav1.7) function. In some examples, the disclosed peptides comprise three to twenty amino acids and include the amino acid sequence KMD. Also disclosed are methods of decreasing nociception including administering an effective amount of one or more disclosed peptides to a subject in need thereof, such as a subject experiencing chronic pain.