A study published in Molecular Neurobiology indicates that, combined with current therapies, it can prevent damage to the central nervous system
Photo: Flavia Polo
After four years of research, Rodrigo Braccini’s thesis was published in the international journal Molecular Neurobiology. In a partnership between PUCRS’ Institute of Toxicology and Pharmacology, the Brain Institute of Rio Grande do Sul and the Teaching and Research Institute of the Santa Casa of Belo Horizonte, and advised by Dr. Maria Martha Campos, Braccini seeks an alternative for the treatment of multiple sclerosis using a molecule derived from the armed spider.
In 2015, during his master’s degree research, Braccini found that the Phα1β molecule, derived from the Phoneutria nigriventer spider, popularly known as armed spider (in Portuguese, armadeira), showed anti-inflammatory activity in mice with hemorrhagic cystitis and produced analgesia (an already known effect of the molecule). Thus, in his doctorate, the idea was to test CTK 01512-2, a recombinant version of Phα1β – i.e., with the peptide being produced from a host (bacterium) – in an animal model of multiple sclerosis, also technically known as experimental autoimmune encephalomyelitis. In addition, the effects produced by CTK 01512-2 were compared with those of ziconotide, a drug clinically used for chronic pain, and fingolimod, a drug used to treat multiple sclerosis.
Thus, the study evaluated behavioral (pain, memory, motor coordination, neurological signs and symptoms), histological (inflammatory infiltrate, demyelination), biochemical (pro-inflammatory and anti-inflammatory markers), cellular (astrocyte activation and microglia) and imaging (microPET, glucose metabolism) parameters in mice with multiple sclerosis. “The results, in short, indicate that CTK 01512-2 significantly improved the neuroinflammatory responses evoked in the animal model of multiple sclerosis, with superior efficacy when compared to ziconotide; and superior therapeutic effects when compared to fingolimod, in parameters such as memory, inflammatory infiltrate, demyelination, leptin and IL-10 secretion (anti-inflammatory and neuroprotective marker),” says the author of the study.
Multiple sclerosis is a chronic and demyelinating neuroinflammatory disease that affects the central nervous system (brain and spinal cord). This disease usually affects young adults between 20 and 40 years of age and leads to almost irreversible physical and mental incapacity. Up to the present time, there is no cure.
Therefore, the author suggests that, in the near future, CTK 01512-2 can be used in combination with current therapies for multiple sclerosis as a strategy of axonal protection (protection of a part of the neuron – the axon) in order to avoid damages to the central nervous system. The next step is to evaluate the chronic toxicity of the molecule, i.e. if it has adverse effects in the long run. As-yet unpublished results showed that there was no acute (i.e. short-term) toxicity.
Graduated in Pharmacy from PUCRS, Braccini holds master’s and doctoral degrees from the Graduate Program in Medicine and Health Sciences in the area of Biochemical and Molecular Pharmacology. The co-authors of the study are Samuel Greggio, Gianina Teribele Venturin, PUCRS Senior Vice President Jaderson Costa da Costa, Marcus Vinicius Gomez and Maria Martha Campos.
