Lab-designed chimeric protein shows beneficial effects in animal models of Alzheimer’s disease

A research team at the Institut de Neurociències of the Universitat Autònoma de Barcelona (INc-UAB) has developed a new protein capable of improving memory and reducing tau protein levels in animal models of Alzheimer’s disease. The new compound—HEBE, generated by fusing three proteins—represents a new approach in the search for new strategies to tackle the disease.

Until now, therapies focused on a single protein have had limited success, due to the complexity of the biological processes involved in aging and neurodegeneration. Now, the research groups Gene therapy for diseases affecting the CNS, Gene therapy strategies for neurometabolic diseases, Systems pharmacology and bioinformatics and Neurobiology of Alzheimer’s disease have combined their areas of expertise to work together in the investigation of therapeutic alternatives.

The result has been the development of HEBE, a chimeric protein made up of three proteins: s-Klotho (s-KL), sTREM2 and TIMP2, which in previous studies have been found to have positive effects in counteracting the effects of the disease.

The research team carried out the binding of the three proteins using computer simulations, and subsequently, confirmed their stability and efficacy in tests in cells and in murine models of Alzheimer’s disease. Their research is published in the journal Biomedicine & Pharmacotherapy.

The results demonstrate that mice treated with the chimeric protein show an improvement in memory and a reduction in the levels of the tau protein, one of the main indicators of the disease. The study has also observed a reduction, although not significant, in the levels of beta-amyloid, the other protein that is also implicated.

“HEBE represents a step forward in the development of new therapeutic strategies against Alzheimer’s disease,” explains Jon Esandi, INc-UAB researcher and first author of the study.

“The results we present show the potential of HEBE and pave the way for its possible application in the clinic,” says Miguel Chillón, coordinator of the research.

A research team at the Institut de Neurociències of the Universitat Autònoma de Barcelona (INc-UAB) has developed a new protein capable of improving memory and reducing tau protein levels in animal models of Alzheimer’s disease. The new compound—HEBE, generated by fusing three proteins—represents a new approach in the search for new strategies to tackle the disease.

Until now, therapies focused on a single protein have had limited success, due to the complexity of the biological processes involved in aging and neurodegeneration. Now, the research groups Gene therapy for diseases affecting the CNS, Gene therapy strategies for neurometabolic diseases, Systems pharmacology and bioinformatics and Neurobiology of Alzheimer’s disease have combined their areas of expertise to work together in the investigation of therapeutic alternatives.

The result has been the development of HEBE, a chimeric protein made up of three proteins: s-Klotho (s-KL), sTREM2 and TIMP2, which in previous studies have been found to have positive effects in counteracting the effects of the disease.

The research team carried out the binding of the three proteins using computer simulations, and subsequently, confirmed their stability and efficacy in tests in cells and in murine models of Alzheimer’s disease. Their research is published in the journal Biomedicine & Pharmacotherapy.

The results demonstrate that mice treated with the chimeric protein show an improvement in memory and a reduction in the levels of the tau protein, one of the main indicators of the disease. The study has also observed a reduction, although not significant, in the levels of beta-amyloid, the other protein that is also implicated.

“HEBE represents a step forward in the development of new therapeutic strategies against Alzheimer’s disease,” explains Jon Esandi, INc-UAB researcher and first author of the study.

“The results we present show the potential of HEBE and pave the way for its possible application in the clinic,” says Miguel Chillón, coordinator of the research.