A novel dementia vaccine targeting three B cell epitopes of Pathological α-Synuclein

A potential preventive vaccine against Dementia Lew Body and Parkinson's disease moves from the mouse model of Synucleinopathies to the IND enabling studies

ORANGE COUNTY, Calif., Nov. 28, 2022 /PRNewswire/ -- Early this year, the scientists from the Institute for Molecular Medicine (IMM), their collaborators from the University of California, Irvine (UCI), and the National Institute on Aging (NIA) reported on the efficacy of four DNA vaccines based on the universal MultiTEP platform and targeting various regions of pathological α-Synuclein in a mouse model of Dementia Lewy Body (DLB) and Parkinson disease (PD) (PMID: 35013319). The most effective nucleic acid vaccine, PV-1950D, generated antibodies specific to three regions of α-Synuclein simultaneously, reduced the aggregation of this pathological molecule, and improved motor deficits in the mouse model of disease. In a new study published in the International Journal of Molecular Sciences (PMID: 35682759), two co-first-author scientists from IMM, Karen Zagorsky, Ph.D., and Gor Chailyan, Ph.D., along with the team of collaborators from IMM, UCI, and the Laboratory of Neurogenetics, NIA, report on the development of the same vaccine in the form of the recombinant protein, PV-1950R, formulated in adjuvant.

A pharmaceutical scientist, Dr. Zagorski, commented: "Dementia is one of the biggest problems affecting the health of the aging population. Currently, about 1.4 million people in the US have been diagnosed with DLB, and PD affects an estimated one million individuals. Development of a safe and immunogenic preventive vaccine against these diseases is one of the goals of our team." His co-first author, an analytical chemist and vaccine developer, Dr. Chailyan added: "IMM recently manufactured cGMP grade human Tau vaccine, AV-1980R/A using funding from U01 AG060965 NIH program. Using the knowledge we gained, we will manufacture cGMP PV-1950R drug product and use it in IND-enabling safety/ toxicology studies before testing this preventive vaccine in people at risk of DLB."

Several monoclonal anti-α-synuclein antibodies and two active vaccines have been evaluated in clinical trials. The IMM team believes that due to the need for frequent administration of high-concentration monoclonal anti-α synuclein antibodies, it is impractical to use them for preventive treatment in asymptomatic individuals. As to already tested in phase 1 active PD01A and UB312 vaccines the newly developed under the AG020241 NIA program PV-1950R/A vaccine differs from both - it has the potential (i) to induce therapeutically potent concentrations of antibodies specific not to one, but to the three different regions of pathological α-synuclein, and (ii) to overcome immunosenescence in the elderly by activating their memory T helper cells specific to the eleven different Th epitopes incorporated into the universal MultiTEP platform.

IMM is a non-profit research institute created to understand, prevent, and cure chronic human diseases, including Dementia Lewy Body, Parkinson's disease, and Alzheimer's disease. IMM is advancing the MuliTEP, a universal vaccine platform technology that supports the development of multiple vaccine designs based on DNA, RNA, or recombinant proteins.

This press release contains forward-looking statements that are often identified by the words "may", "might", "believes", "thinks", "anticipates", "plans", "expects", "intends" or other similar expressions. In addition, expressions of our strategies, intentions, or plans are also forward-looking statements. Although forward-looking statements contained herein are based upon what IMM believes are reasonable assumptions, there can be no assurance that forward-looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements.

SOURCE Institute for Molecular Medicine