Studies show Cyto-111 enables the delivery of antibodies to previously intraneuronal targets without the need for Viral Vector or Transmission
Supports the development of new approaches to the treatment of a number of neurological diseases
NEW YORK, January 07, 2021 (GLOBE NEWSWIRE) – Tha CytoDel, Inc. (“CytoDel” or “the Company”), a private corporation, 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 with 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 view that the C1ad a previously reported delivery vehicle could be used to transport therapeutic proteins into the neuronal cytosol, developed and researched by Dr. Ichtchenko conducted a potential treatment for botulism based on intracellular inhibition of BoNT subtype A1 (LC / A1) light chain metalloprotease. 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. follow up in vitro testing of therapeutic mechanisms, efficacy studies were performed in mice, guinea pigs and rhesus macaque monkeys.
The study showed that a detailed biomaterial consisting of cargo that inhibited the action of one habitat (sdAb; B8) was attached to the C1ad delivery vehicle (forming B8C1ad or Cyto-111) enters neurons and protects SNARE proteins by inhibiting LC / A1 catalytic activity in situ. Post-symptomatic administration of B8C1ad performed antidotal rescue in mice, guinea pigs, and nonhuman primates after a fatal botulism challenge.
According to the study’s authors, “Flexibility in Q1ad a molecular delivery platform offers several benefits for the rapid generation of new treatments for brain disorders. In particular, LC presynaptic localization suggests that this therapeutic approach will be particularly effective in the treatment of synaptopathies involving active zone proteins. In fact, the platform can be effectively redirected toward other protein targets by replacing or adding single-domain antibodies or other protein groups. ”
The study concluded, “These data demonstrate that atoxic BoNT derivatives can be used to deliver therapeutic protein groups to the neuronal cytoplasm where they bind and neutralize intracellular targets in experimental models. The prevalence of this platform could allow antibodies and other protein-based therapy to be targeted to previously inaccessible intraneuronal targets. ”
“This is a unique study in converting the potentiating power of botulinum neurotoxins into medications. The approach used to convert botulinum toxins into a type of Trojan horse that delivers cargo to neurons with great potential for future drug development, ”said Thomas C. Südhof, MD, Senior professor in the School of Medicine in the Department of Molecular and Cellular Psychology, and in Neuro, Psychology and Behavioral Studies at Stanford University, 2013 Nobel Prize winner in Psychology / Medicine, Medical Institute researcher Howard Hughes, and Chair of the CytoDel Scientific Advisory Board.
“We are delighted that this data will be published in a popular peer-to-peer journal as it represents the culmination of years of research with the aim of finding a solution to deal effectively with toxins. botulinum with weapons. Importantly, this groundbreaking data is the result of the efforts of researchers from several reputable institutions including the NYU Grossman School of Medicine, the Cummings School of Medicine at Tufts University, and the U.S. Army Medical Research Institute for Chemical Defense , without the hard work. and it would not be possible to achieve this, ”said Phillip A. Band, Ph.D., Research Professor in the Departments of Orthopedic Surgery, Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, and co. engineer, co-founder and CEO of CytoDel.
“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 breakdown because no other laboratory has 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 brain diseases, ”said Dr.
In Botulinum Neurotoxin
Botulinum neurotoxin (BoNT) is considered a Tier 1 mechanism of mass destruction. BoNT has no smell or taste, one gram is enough to kill 1 million people by inhaling or inhaling, and there are currently no cures to reverse symptoms . All currently available treatments for botulism are antibody products that can only neutralize toxins in systemic circulation. Once the toxin has entered the neurons controlling relief, usually 24-72 hours after exposure to the dose, results are based on a non-antibody. effective. Normal antibodies cannot access toxins already inside neurons, so BAT® (Botulism AntiToxin, a product of Emergent BioSolutions), the only FDA-approved antitoxin, is not effective while the toxin remains in circulation.
About Cyto-111
Cyto-111 uses the CytoDel Intraneuronal Delivery Platform to deliver antibody within BoNT-intoxicated neurons, thus allowing salvage after the toxin enters neurons and causes symptoms. This “Trojan horse” approach uses an inactive reactive BoNT derivative to transport the antibody within the BoNT alcohol neurons. Cyto-111 can dramatically reverse symptoms because it can deliver its antibody to toxins that are already inside the neuron. In biodefense situations, this significantly extends the time after onset when treatment can reverse symptoms and save lives by reducing the need for long-term artificial relief. As a treatment for naturally occurring botulism, Cyto-111 extends the therapeutic window beyond the 48-hour limit when BAT has been effective.
About CytoDel
CytoDel is a private biopharmaceutical company that uses molecular biology equipment in the 21st century to produce recombinant products of botulinum neurotoxin that are tailored for specific applications. The Company’s proprietary technology allows CytoDel to manipulate the BoNT molecule to develop next-generation BoNT products and a drug delivery vehicle that can deliver therapeutic molecules inside neurons. CytoDel’s flagship program is focused on developing BioBetter BoNT medications, offering a safety margin and improved efficacy results for the treatment of large muscles and muscle groups. A second program uses intraneuronal delivery for Biodefense, and CytoDel is also developing programs for the treatment of nervous system disorders and chronic pain. For more information, visit www.cytodel.com.
* Both Drs. Ichtchenko and Band have financial interests from NYU Grossman School of Medicine in CytoDel and Dr. Band serves on their management team. These arrangements are governed by NYU Langone Health policies and practices.
Contact:
Allison Moulard
Email: [email protected]
Phone: 510 823 0501
Anne Marie Fields
Email: [email protected]
Phone: 201-315-8118