Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report.

Schwann cells are essential for the maintenance and function of motor neurons, axonal networks, and the neuromuscular junction. In amyotrophic lateral sclerosis, where motor neuron function is progressively lost, Schwann cell function may also be impaired. Recently, important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported. This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles, marking, to our knowledge, the first instance of such treatment. An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis. After initial diagnosis, the patient underwent a combination of generic riluzole, sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis, and taurursodiol. The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function. We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired (senescent) and that exposure of the patient's Schwann cells to allogeneic Schwann cell-derived exosomal vesicles, cultured expanded from a cadaver donor improved their growth capacity in vitro. After a period of observation lasting 10 weeks, during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored, the patient received weekly consecutive infusions of 1.54 × 10 12 (×2), and then consecutive infusions of 7.5 × 10 12 (×6) allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco's phosphate-buffered saline. None of the infusions were associated with adverse events such as infusion reactions (allergic or otherwise) or changes in vital signs. Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend. A more sensitive in-house assay suggested possible inflammasome activation during the disease course. A trend for clinical stabilization was observed during the infusion period. Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles. Initial findings suggest that this approach is safe.

Rivalry between Humans and Coronaviruses: Unanticipated Impact of Omicron.

With our prior Commentary we discussed the rivalry between ideation (humans) and mutations (viruses), (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439168/), and more specifically, we described and compared two means of adaptability: collective and focused ideation for humans and self-serving mutation for viruses. The amazingly fast development of new effective and safe vaccines and drugs requires the humankind's most sophisticated form of ideation ability to respond to threatening stressors such as a dangerous virus like SARS-CoV-2. The essence of what makes us human is that human ideation requires a society of people working towards the same goal and is interdependent on socialization for the sustainability of humankind. In contrast, viruses mutate alone and "selfishly". The best fit virus for a particular environment, for a particular host, eliminates the competition through successive mutations. The Omicron variant of concern (VoC) is a great example for how higher transmissibility and perhaps, stochasticity, can drive the transmissive success of a virus across an entire host species like humans. With this review, we describe how Omicron has impacted the COVID-19 pandemic in an unanticipated way that could bring an end to it.

Pregnancy, a unique case of heterochronic parabiosis and peripartum cardiomyopathy.

Introduction: A loss of endogenous stem cells capable of tissue repair and regeneration drives the biological process that we recognize as "aging". Recovery of stem cell-mediated repair and regenerative functions in aged animals has been reported in murine heterochronic parabiosis experiments. Objectives: Herein we will review how pregnancy is an unusual form of heterochronic parabiosis, as the placenta prevents the exchange of most blood cells between parabionts. Instead, plasma and its content, including small extracellular vesicles, can readily cross the placental barrier. These nanosized extracellular vesicles are readily produced by the placenta, amnion, fetus and mother, and are essential for fetal organogenesis, growth and the progression of a healthy pregnancy. If defective, these extracellular vesicles can cause havoc such as in the case of peripartum cardiomyopathy. We will also review how these extracellular vesicles impact the mother substantially (including cardiac function) in the parabiosis of pregnancy. Conclusion: Extracellular vesicles generated during the course of a healthy pregnancy are essential for organogenesis and fetal growth, and also for maternal tissue repair and regeneration, and might be defective or deficient in pregnancies that result in peripartum cardiomyopathy.

Rivalry between human ideation and virus mutation: two competing means of sustainability.

For the first time in human history, obtaining a COVID-19 vaccine has become essential for the sustainability of our species. As an amazing product of collective ideation, remarkably safe and efficient vaccines have been invented, tested, distributed, and administered to the population on a voluntary basis. The fast-mutating individual behavior of the virus is probably guided by a similar goal of the sustainability of the species. With this commentary, we analyze and compare two means of sustainability through adaptability: collective ideation in the case of humans and individual mutations in the case of viruses - two very different species whose behaviors are driven by sustainability.