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"The AAN Annual Meeting offers top-tier education in an array of learning formats, covering nearly every topic and specialty imaginable, all the valuable CME you need for the year, and the most cutting-edge science across all specialties." The meeting will take place in Boston this year from April 22nd-27th. We are excited to have been invited to share some of our notable research in the form of platform talks and posters. The below will be presented by our Tisch MSRCNY researchers.
Efficacy of Intrathecal Mesenchymal Stem Cell-Neural Progenitor Therapy in Progressive MS: Results from a Phase II Clinical Trial
Presented by Saud Sadiq, MD, FAAN
MSC-NPs are bone marrow-derived cells with trophic and immunomodulatory properties with therapeutic potential in MS. In an open-label phase I clinical study in 20 progressive MS subjects, the safety and tolerability of the treatment was demonstrated, and was associated with functional neurological improvement, particularly in ambulatory patients.
These results suggest that IT-MSC-NP treatment may correlate with therapeutic response in a subgroup of MS patients.
Immunological Response to COVID-19 Vaccine Boosters in Multiple Sclerosis Patients Treated with anti-CD20 Therapy
Presented by Roberto Alfonso, PhD
Vaccines against SARS-CoV-2 (CoV-2) have been efficient in blocking severe disease and death in immunocompetent and immunocompromised individuals. Nevertheless, aCD20-MS patients are at high risk of diminished vaccine response due to therapy-induced B-cell depletion. In contrast, a strong T-cell response after the initial two-dose vaccination has been observed in these individuals which could be at least partially responsible for their observed immune protection. The immune response to COVID-19 vaccine boosters in aCD20-MS patients remains largely unknown.
These results highlight that despite the potential development of a severely impaired humoral response in antiCD20-treated MS patients even after multiple COVID-19 vaccine doses, a sustained strong T-cell response might provide some level of immune protection against severe CoV-2 infection.
Cerebrospinal Fluid Biomarkers Associated with Intrathecal Cell Therapy in Patients with Progressive Multiple Sclerosis
Presented by Cara Kizilbash
MSC-NPs are a bone marrow-derived population of cells with trophic and immunomodulatory properties with therapeutic potential in MS. A phase II randomized, double-blind, placebo-controlled clinical trial was performed to investigate whether multiple intrathecal (IT) injections of autologous MSC-NPs was associated with clinical efficacy. Study subjects received either 6 IT injections of autologous MSC-NPs or 6 placebo injections spaced 2 months apart. In the crossover study design, subjects treated with placebo in the first year were treated with MSC-NPs in the second year, and vice versa. Safety and clinical efficacy will be reported elsewhere.
These results identify multiple CSF biomarkers of IT-MSC-NP treatment that may correlate with therapeutic response to this novel cell therapy in MS
Long-term Culture of Cerebral Organoid Reveals Disruption of Glial Cell Differentiation and Glutamate Excitotoxicity in Multiple Sclerosis.
Presented by Tanmay Mehta
MS is an auto-immune disease characterized by inflammation, demyelination and neural degeneration. It has been shown that environmental and genetic factors contribute to the development of MS, however, the etiology of this condition is unknown. Our previous research showed that organoids from PwMS display an exhaustion of the neural progenitor pool and an increase in neurogenesis. Here, we studied differentiation of neurons into glutamate and GABAergic neurons as glutamate excitotoxicity has been proposed to lead to inflammation and neuronal injury in MS. We also investigated glial cell differentiation and maturation in astrocytes and oligodendrocytes to determine their role in MS pathogenesis.
Mature cerebral organoids developed from PwMS represent an innovative tool to study MS and allowed us to detect a defect of astrocyte and oligodendrocyte differentiation and maturation as well as an imbalance of GABA/Glutamate release in MS organoids
Healthy astrocytes provide neuroprotection against apolipoprotein B-100-induced motor neuron degeneration
Presented by Rose Griffin
ALS is a devastating neurodegenerative disease which results in motor neuron degeneration in the brain and spinal cord. Our previous research identified ApoB as a neurotoxic factor as it is upregulated in the cerebrospinal fluid (CSF) of ALS patients and can induce motor disability and motor neuron degeneration in vivo in mice, as well as death of human motor neurons in vitro. Here, we investigate whether astrocytes play a role in exacerbating or protecting against ApoB-induced motor neuron death.
Healthy astrocytes appear to protect motor neurons from the neurotoxic effects of ApoB by reducing uptake of ApoB into motor neurons. This suggests that intrinsic defects in ALS astrocytes disrupt this neuroprotective function, leaving motor neurons susceptible to ApoB-mediated degeneration. Future experiments will seek to elucidate how astrocyte dysfunction contributes to motor neuron degeneration in ALS
Bax inhibitor protects against apolipoprotein B-100-induced human motor neuron degeneration in vitro
Presented by Ivy Gao
ALS is a progressive neurodegenerative disease characterized by motor neuron loss. Its sporadic form is the most prevalent, afflicting 90% of those with ALS. We previously showed that ApoB is a neurotoxic protein increased in sALS patient CSF that induces motor neuron degeneration. Mice injected intrathecally with ApoB exhibit the same motor neuron degeneration as those injected with sALS CSF, and cultured human motor neurons treated with pathogenic concentrations of ApoB undergo cell death. As Bax is a common pro-cell death regulator, we investigate in vitro whether ApoB-induced motor neuron death is Bax-dependent.
Our in vitro studies show that ApoB-induced human motor neuron death is mediated by Bax activation, which can be prevented with a Bax inhibitor. This suggests Bax-dependent apoptosis is a likely mechanism of ApoB-induced motor neuron degeneration. Bax inhibitors may have therapeutic value in ALS
Recombinant antibodies binding to cytoskeletal structural proteins in post Covid-19 vaccination demyelination syndromes
Presented by Amol Raisingani
Vaccines against SARS-COV-2 elicit an antibody response and reduce severity of infection, but rarely are associated with adverse neurological events. We report on two such patients who developed post-vaccinal demyelinating syndromes.
Our study shows that in patients with vaccination induced demyelinating disorders, anti-SARS-COV-2 S1 spike antibodies may be detected in CSF. Recombinant antibodies derived from CSF clonally expanded B-cells reacted with cytoskeletal keratin type II protein and GFAP. However, further investigation with the antibodies needs to be performed to better postulate a mechanism for demyelination.