Disclosed are the use of neuregulin proteins in preparing a medicine for preventing, treating or delaying preserved ejection fraction cardiac failure in mammals, and a method for using the medicine. Also provided in the present invention is a method for preventing, treating or delaying preserved ejection fraction cardiac failure in mammals, comprising using the medication containing the neuregulin proteins in a special population having the disease or being at risk of having the disease.

This invention relates to treatment of neuroinjury in a post-acute window or in a chronic period following neuroinjury.

Composite nerve guides for nerve regeneration are provided, wherein the composite guide comprise a nerve graft and a nerve conduit continuing an active agent that promote axon regeneration. The devices can provide structural supports to guide nerve regeneration and locally deliver an active agent (e.g., glial cell-line derived neurotrophic factor (GDNF) and/or glial growth factor 2 (GGF2) to injured nervous system tissue upon implantation in a subject. Methods of treatment using such devices are also provided.

Composite nerve guides for nerve regeneration are provided, wherein the composite guide comprise a nerve graft and a nerve conduit continuing an active agent that promote axon regeneration. The devices can provide structural supports to guide nerve regeneration and locally deliver an active agent (e.g., glial cell-line derived neurotrophic factor (GDNF) and/or glial growth factor 2 (GGF2) to injured nervous system tissue upon implantation in a subject. Methods of treatment using such devices are also provided.

The invention features methods of treatment and diagnosis using NRG-2 polypeptides, nucleic acid molecules, and antibodies. The invention also provides novel NRG-2 polypeptides and nucleic acid molecules.

Provided herein are methods and compositions for treating disease-states associated with presence of increased number of ErbB4+ pro-inflammatory macrophages in a subject in need thereof. The methods include providing an activator of ErbB4 and administering a therapeutically effective amount of the activator to the subject. The compositions include an activator of ErbB4. In one embodiment, the activation of ErbB4 is Neuregulin-4.

The invention relates to treatment and prevention of heart failure in a mammal. The invention provides a dosing regimen whereby the therapeutic benefits conferred by administration of peptide comprising an epidermal growth factor-like domain, e.g., a neuregulin such as glial growth factor 2 (GGF2) or a functional fragment thereof, are maintained and/or enhanced, while concomitantly minimizing any potential side effects.

The present invention refers to soluble Neuregulin-1 isoforms representing Posttranslational Neuregulin-1 modifications as medication in cognition-related neurological disorders, in particular schizophrenia, Alzheimer's and Parkinson's diseases.

Multiple sclerosis (MS) is characterized by immune mediated neurodegeneration that results in progressive, life-long neurological and cognitive impairments. Yet, the endogenous mechanisms underlying MS pathophysiology are not fully understood. Here, we provide compelling evidence that associates dysregulation of neuregulin-1 beta 1 (Nrg-11) with MS pathogenesis and progression. In the experimental autoimmune encephalomyelitis (EAE) model of MS, we demonstrate that Nrg-11 levels are abated within spinal cord lesions and peripherally in the plasma and spleen during presymptomatic, onset and progressive course of the disease. We demonstrate that plasma levels of Nrg-11 are also significantly reduced in individuals with early MS and is positively associated with progression to relapsing-remitting MS. The functional impact of Nrg-11 downregulation preceded disease onset and progression, and its systemic restoration was sufficient to delay EAE symptoms and alleviate disease burden. Intriguingly, Nrg-11 therapy exhibited a desirable and extended therapeutic time window of efficacy when administered prophylactically, symptomatically, acutely or chronically. Using in vivo and in vitro assessments, we identified that Nrg-11 treatment mediates its beneficial effects in EAE by providing a more balanced immune response. Mechanistically, Nrg-11 moderated monocyte infiltration at the blood-central nervous system interface by attenuating chondroitin sulfate proteoglycans and matrix metalloproteinase-9. Moreover, Nrg-11 fostered a regulatory and reparative phenotype in macrophages, T helper type 1 (Th1) cells and microglia in the spinal cord lesions of EAE mice. Taken together, our new findings in MS and EAE have uncovered a novel regulatory role for Nrg-11 early in the disease course and suggest its potential as a specific therapeutic target to ameliorate disease progression and severity.

Disclosed herein are compositions and methods for the treatment of otic disorders with immunomodulating agents and auris pressure modulators. In these methods, the auris compositions and formulations are administered locally to an individual afflicted with an otic disorder, through direct application of the immunomodulating and/or auris pressure modulating compositions and formulations onto the auris media and/or auris interna target areas, or via perfusion into the auris media and/or auris interna structures.