PAS002 Vaccine Shows Efficacy in MS Mouse Model

Pasithea Therapeutics investigational multiple sclerosis vaccine, PAS002, effectively delayed disease onset and reduced disease severity in a mouse model of the neurodegenerative condition, according to data from a preclinical study.

The vaccine, which is designed to promote immune tolerance to a specific myelin protein, also reduced the severity of relapses and helped the animals gain weight, indicating a better overall health status.

“Although early stage data, we’re thrilled with the results of this study and the strong preclinical efficacy data of our tolerizing approach,” Tiago Reis Marques MD, PhD, CEO of Pasithea, said in a press release.

While regular vaccines are designed to train the body to develop an immune response against a particular pathogen, tolerizing vaccines essentially do the opposite, acting as a “reverse vaccine.” These vaccines instead train the immune system to tolerate a molecule, suppressing an unwanted immune response against it.

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In multiple sclerosis (MS), the immune system mistakenly attacks myelin, the fatty protective substance that surrounds nerve cells to accelerate the transmission of electric signals. PAS002 aims to prevent these damaging autoimmune attacks against myelin by helping the immune system tolerate a protein called GlialCAM.

GlialCAM is a molecule that is found particularly in oligodendrocytes, the cells chiefly responsible for making myelin. According to a study published earlier this year, this protein shares molecular similarities with a protein component of the Epstein-Barr Virus (EBV), leading the immune system to target GlialCAM when the attack was instead directed against EBV.

Through this mechanism, EBV infections may trigger the mistaken autoimmune attacks on myelin, which may help explain the strong link between EBV infection and MS risk.

Based on these findings, Pasithea developed its PAS002 vaccine to promote immune tolerance to GlialCAM. The medication is a DNA vaccine, which means it delivers GlialCAM’s DNA, and the body then uses its own cellular machinery to generate the GlialCAM protein. Once produced, the protein is seen by the immune system as self (being produced naturally in the body), which helps immune cells recognize it as harmless.

Pasithea hopes that in helping the immune system accept GlialCAM, PAS002 will prevent the attacks that cause myelin loss in the brain and spinal cord, thereby reducing disease severity and MS relapses.

PAS002’s development has been under the leadership of Lawrence Steinman, MD, Pasithea’s chairman and a professor at Stanford University in California. Steinman was behind the development of Tysabri (natalizumab), an approved MS therapy, and was one of the authors in the EBV study.

Collaboration with Hooke Laboratories

Earlier this year, Pasithea announced that preclinical testing of its vaccine in the experimental autoimmune encephalomyelitis (EAE) mouse MS model would be conducted in collaboration with Hooke Laboratories in Massachusetts.

Now, proof-of-concept findings from these preclinical studies show that PAS002 can reduce disease severity in the EAE model.

The mice received injections of PAS002 or a solution containing no active medication, called a vehicle. The injections were given into the muscle (intramuscular) on days on days 0, 3, 7 and 10 after disease induction, at which point disease symptoms were not yet evident.

Results indicated that PAS002 treatment was able to prevent the disease from manifesting in 50% of mice. Also, in animals that developed symptoms, the treatment also significantly reduced peak disease severity and relapse severity, compared with the vehicle treatment.

Treated mice also experienced a significant increase in body weight, and onset of limb paralysis was delayed significantly.

“The results of this study show that this technology has the potential to tolerize to GlialCAM, a myelin molecule that has molecular similarity to the Epstein Barr Virus that triggers MS,” Steinman said.

“We have now filed a provisional patent application and we will continue our work to improve our constructs, testing our tolerizing approach in other preclinical EAE models and progress this drug development,” Marques said.

According to Pasithea, full data from the study will be shared at conferences and will be submitted for publication.