A comparison of human natural monoclonal antibodies and aptamer conjugates for promotion of CNS remyelination: where are we now and what comes next?

INTRODUCTION: Multiple sclerosis (MS) is a chronic and progressive inflammatory demyelinating disease of the human central nervous system (CNS) and is the most common disabling neurological condition in young adults, resulting in severe neurological defects. No curative or long-term progression-inhibiting therapy has yet been developed. However, recent investigation has revealed potential strategies that do not merely modulate potentially pathogenic autoimmune responses, but stimulate remyelination within CNS lesions. AREAS COVERED: We discuss the history and development of natural human IgM-isotype immunoglobulins (HIgMs) and recently-identified aptamer-conjugates that have been shown to enhance endogenous myelin repair in animal models of demyelination by acting on myelin-producing oligodendrocytes (OLs) or oligodendrocyte progenitor cells (OPCs) within CNS lesions. We also discuss future development aims and applications for these important novel technologies. EXPERT OPINION: Aptamer conjugate Myaptavin-3064 and recombinant human IgM-isotype antibody rHIgM22 regenerate CNS myelin, thereby reducing axonal degeneration and offering the potential of recovery from MS relapses, reversal of disability and prevention of disease progression. Advancement of these technologies into the clinic for MS treatment is therefore a top priority. It remains unclear to what extent the therapeutic modalities of remyelinating antibodies and aptamers may synergize with other currently-approved therapies to yield enhanced therapeutic effects.

Volumetric analysis of olfactory neuroblastoma skull base laterality and implications on neck disease.

OBJECTIVE: To determine if the laterality of primary tumors in patients with olfactory neuroblastoma (ONB) influenced the pattern and development of neck disease. METHODS: Using a retrospective cohort study design from 1994 to 2015, the primary tumors of patients who either presented with or developed neck disease were volumetrically analyzed using iPlan software (version 3.0.0, BrainLAB, Feldkirchen, Germany) by two independent observers. Agreement of volume-derived sidedness was assessed with a kappa statistic, whereas agreement in volume-derived degree of tumor laterality was evaluated with an intraclass correlation coefficient. A one-sample t test was used to assess the difference in dominant percentage between the two observers. RESULTS: Sixty-one patients with histological diagnosis and treatment of ONB at our institution were identified. Twenty-four patients exhibited neck involvement, 13 of whom could be volumetrically analyzed. Tumors that were greater than 75% eccentric to one side all exhibited contralateral disease, whereas the majority of unilateral neck disease was associated with relatively midline masses. Within the entire cohort, ipsilateral level 2 lymph nodes displayed the highest involvement (83%, 20 of 24), followed by ipsilateral level 1 (54%, 13 of 24), contralateral level 2 (46%, 11 of 24), contralateral level 1 (21%, 5 of 24), and ipsilateral level 3 (21%, 5 of 24). CONCLUSION: Ipsilateral neck involvement frequently was observed; however, the degree of ONB primary site laterality did not appear to have implications on the development of contralateral neck disease. Therefore, when considering elective therapy to the neck, ONB laterality should not be used to justify unilateral neck treatment. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:864-870, 2018.