Tha CytoDel, Inc. (“CytoDel” or “The Company”), a private corporate entity, today announced the publication of preclinical data on the Company’s flagship product, Cyto-111, in the peer-reviewed journal, Science Translational Medicine. The full text of the article entitled, “Neuronal Delivery of Antibodies has therapeutic effects in animal models of botulism,” can be found here.
Cyto-111 was born, expressed and purified in the laboratory of Konstantin Ichtchenko, Ph.D., NYU Grossman School of Medicine, Department of Biochemistry and Molecular Pharmacology, who was the lead investigator in the study, which supported by grants from the National Institute of Infectious and Infectious Diseases (NIAID), a division of the National Institutes of Health (NIH).
Based on Dr. Ichtchenko’s idea that the previously reported C1ad delivery vehicle could be used to transport therapeutic proteins into the neuronal cytosol, researchers led by Dr. Ichtchenko developed a potential treatment for botulism based on intracellular inhibition on the BoNT subtype A1 light chain. metalloprotease (LC / A1).
The main objective of the antidote study was to develop post-symptomatic botulism and to test the potential of rescuing symbolic animals with a lethal dose challenge of BoNT. Following in vitro testing of therapeutic mechanisms, efficacy studies were performed in mice, guinea pigs, and rhesus macaque monkeys.
The study showed that a precise biomedicine consisting of cargo that inhibits the action of a single domain (sdAb; B8) can be connected to the C1ad delivery vehicle (generating B8C1ad or Cyto-111) enter neurons and protect SNARE proteins by inhibiting LC / A1 catalytic activity. in situ.
Post-symptomatic administration of B8C1ad provided antidotal rescue in mice, guinea pigs, and nonhuman primates following the challenge of lethal botulism.
According to the authors of the study, “The flexibility of the C1ad molecular delivery platform offers several benefits for rapid generation of new therapies for brain disorders. In particular, LC presynaptic resection suggests the therapeutic approach this is particularly effective in the treatment of synaptopathies that include active zone proteins.In fact, the platform can be effectively redirected towards other protein targets by replacing or adding single domain antibodies or other protein groups. “
The study concluded “These data indicate that BoNT atoxic derivatives can be used to deliver therapeutic protein groups to the neuronal cytoplasm where they bind and neutralize intracellular targets in experimental models. The capability of this platform could deliver antibodies and other therapeutic-based proteins to previously unattainable intraneuronal targets. “
“This is a unique study in converting the potency of lethal botulinum neurotoxins into medications. The technique used to convert botulinum toxins into a type of Trojan horse that delivers cargo to neurons with potential important for future drug development, ”said Thomas C. Südhof, MD, Professor in the School of Medicine in the Department of Molecular and Cellular Psychology, and in Neuro, Psychology and Behavioral Studies at Stanford University , winner of the 2013 Nobel Prize in Geology / Medicine, Howard Hughes Institute of Medicine researcher, and Chair of the CytoDel Scientific Advisory Board.
We are delighted that these data will be published in a peer-reviewed journal as they represent the culmination of years of study with the intention of finding a solution to effectively treat botulinum toxins. weapons. Importantly, this groundbreaking data is the result of the efforts of researchers from several reputable institutions including the NYU Grossman School of Medicine, Tufts University Center for Interventional Medicine, and the U.S. Army Medical Research Institute for Defense Chemically, without their hard work and commitment this achievement would not have been possible. “
Phillip A. Band, PhD, Research Professor, Departments of Orthopedic Surgery, Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, and CytoDel Co-Engineer, Co-Founder and CEO
“Not only have these studies shown that Cyto-111 can be an antidote to botulinum toxins, but they also show the generality of the molecular vehicle in three different species to activate antibodies. safe and effective delivery within neurons through a non-viral device. . This is a very interesting break because no other labs have activated a pathogen within neurons, which is accessible to normal antibodies. This achievement opens the door to the development of new approaches to the treatment of a number of neurological diseases, “said Dr. Band.
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Magazine Reference:
McNutt, PM, et al. (2021) Therapeutic delivery of antibodies exerts therapeutic effect in animal models of botulism. Science Translational Medicine. doi.org/10.1126/scitranslmed.abd7789.