Spinal Cord Stimulation Improved Freezing of Gait and Hypokinetic Dysarthria of a Patient with Dopamine-Resistant Multiple System Atrophy-Parkinsonian Type.

Background: Multiple system atrophy parkinsonian type (MSA-P) patients with resistance to dopamine have highly limited treatment options. This calls for further study of spinal cord stimulation (SCS) as a potential nondopaminergic therapy to improve motor and speech functions of patients with dopamine-resistant parkinsonism. Case Presentation: A 58-year-old male with MSA-P had hypokinetic dysarthria, freezing of gait (FOG), and spinal disc herniation with refractory back pain. SCS was used to treat his refractory back pain. Serendipitously, after the surgery, the patient reported not only a reduction in pain but also rapid improvement of FOG and hypokinetic dysarthria. Conclusion: SCS has been found in some cases to improve FOG and hypokinetic dysarthria. It is necessary to further study the potential of and the mechanism behind SCS as a potential nondopaminergic therapy to improve motor and speech functions of patients with dopamine-resistant parkinsonism.

The unique potency of Cowpea mosaic virus (CPMV) in situ cancer vaccine.

The immunosuppressive tumor microenvironment enables cancer to resist immunotherapies. We have established that intratumoral administration of plant-derived Cowpea mosaic virus (CPMV) nanoparticles as an in situ vaccine overcomes the local immunosuppression and stimulates a potent anti-tumor response in several mouse cancer models and canine patients. CPMV does not infect mammalian cells but acts as a danger signal that leads to the recruitment and activation of innate and subsequently, adaptive immune cells. In the present study we addressed whether other icosahedral viruses or virus-like particles (VLPs) of plant, bacteriophage and mammalian origin can be similarly employed as intratumoral immunotherapy. Our results indicate that CPMV in situ vaccine outperforms Cowpea chlorotic mottle virus (CCMV), Physalis mosaic virus (PhMV), Sesbania mosaic virus (SeMV), bacteriophage Qß VLPs, or Hepatitis B virus capsids (HBVc). Furthermore, ex vivo and in vitro assays reveal unique features of CPMV that makes it an inherently stronger immune stimulant.

A Viral Nanoparticle Cancer Vaccine Delays Tumor Progression and Prolongs Survival in a HER2+ Tumor Mouse Model.

Human epidermal growth factor receptor 2 (HER2) overexpression is associated with aggressive tumors with increased incidence of metastasis and recurrence. Therapeutic antibodies such as Trastuzumab inhibit tumor growth through blockade of HER2 receptors. However, the short lifespan of such therapeutic antibodies necessitates repeat administrations with ensuing cardiac toxicity and development of resistance, while offering no protection against relapse. Cancer vaccines targeting HER2 can overcome these shortcomings of passive immunotherapy by instigating an endogenous and sustained immune response and memory against the cancer antigen. The efficacy of a viral nanoparticle (VNP)-based cancer vaccine is demonstrated here in activating a potent anti-HER2 immune response that delays progression of primary tumors as well as metastases and prolongs survival in mice. The results illustrate that the VNP-based vaccine instigates HER2-specific antibodies as well as effector and memory T cells, which contributes to the effectiveness of the vaccine. Given the highly aggressive course of HER2+ cancers, inhibition of disease progression by such cancer vaccines could provide a critical window for interventions with other adjuvant therapies. Moreover, the immune memory generated by this viral nanoparticle-based cancer vaccine could mitigate relapse of the disease.

Plant viral nanoparticles-based HER2 vaccine: Immune response influenced by differential transport, localization and cellular interactions of particulate carriers.

Cancer vaccines are designed to elicit an endogenous adaptive immune response that can successfully recognize and eliminate residual or recurring tumors. Such approaches can potentially overcome shortcomings of passive immunotherapies by generating long-lived therapeutic effects and immune memory while limiting systemic toxicities. A critical determinant of vaccine efficacy is efficient transport and delivery of tumor-associated antigens to professional antigen presenting cells (APCs). Plant viral nanoparticles (VNPs) with natural tropism for APCs and a high payload carrying capacity may be particularly effective vaccine carriers. The applicability of VNP platform technologies is governed by stringent structure-function relationships. We compare two distinct VNP platforms: icosahedral cowpea mosaic virus (CPMV) and filamentous potato virus X (PVX). Specifically, we evaluate in vivo capabilities of engineered VNPs delivering human epidermal growth factor receptor 2 (HER2) epitopes for therapy and prophylaxis of HER2+ malignancies. Our results corroborate the structure-function relationship where icosahedral CPMV particles showed significantly enhanced lymph node transport and retention, and greater uptake by/activation of APCs compared to filamentous PVX particles. These enhanced immune cell interactions and transport properties resulted in elevated HER2-specific antibody titers raised by CPMV- vs. PVX-based peptide vaccine. The 'synthetic virology' field is rapidly expanding with numerous platforms undergoing development and preclinical testing; our studies highlight the need for systematic studies to define rules guiding the design and rational choice of platform, in the context of peptide-vaccine display technologies.