Gene Therapy May Protect Brain from Age-Related Cognitive Decline

Curated by Claudia Shannon / Research Scientist / ishonest

Researchers from the Universitat Autonoma de Barcelona and the Vall d’Hebron Research Institute, both in Barcelona, Spain, report their findings in the journal Molecular Psychiatry.

The study’s findings are significant because they are the first to show that injecting one dose of Klotho-promoting gene therapy into the central nervous system (CNS) of young mice prevented age-related cognitive decline when they reached old age.

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The researchers also found that the treatment even protected against “age- dependent cognitive decline when mice were treated at old ages.”

The team hopes that the findings will advance research and development of new treatments for neurodegenerative diseases such as dementia based on Klotho, which has already been recognized for its “neuroprotective” role.

Klotho gene and aging

The new research builds on previous work by some of the same team members, in which they showed that the Klotho gene helps to control age-related mechanisms.

In that earlier research, they found that when over-expressed, Klotho increases longevity, and when it is blocked, it speeds up decline in memory and learning.

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For their new study, the team used gene therapy to increase expression of Klotho to raise production of the associated protein.

“The therapy is based on an increase in the levels of this protein in the brain using an adeno-associated viral vector (AAV),” explains Dr. Miguel Chillón, a researcher in biochemistry and molecular biology at both research centers.

AAVs promising for CNS gene therapy

Gene therapy based on AAVs exploit the fact that viruses have a natural ability to enter cells and alter their genetic makeup. The viruses are modified so that they cannot cause disease and can carry the required gene-altering material into cells.

Researchers have been investigating AAVs for 55 years, and their potential as a gene therapy for certain types of genetic disorders have shown much promise in trials.

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However, while many might argue that there are reasons to be optimistic about the safety and effectiveness of AAVs as a vehicle for gene therapy in human patients, there are still many unanswered questions.

Nevertheless, Dr. Assumpció Bosch, a researcher in biochemistry and molecular biology, says that one application of AAVs — when they are used as a gene therapy for the CNS — has trial evidence to suggest that their effectiveness and safety is growing.

Preclinical trials with models of Alzheimer’s

The researchers have licensed their gene therapy to a new company based in the United States and in which the Universitat Autonoma de Barcelona retains an interest.

The purpose of the venture is to raise funding for the completion of preclinical trials with animal models of Alzheimer’s disease that are already underway.

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The researchers hope that this will also pave the way for a gene therapy for neurodegenerative diseases that uses small molecules, or small fragments of the protein, to raise Klotho expression.

“Taking into account that the study was conducted with animals which aged naturally, we believe this could have the therapeutic ability to treat dementia and neurodegenerative disorders such as Alzheimer’s or multiple sclerosis, among others.”

Dr. Miguel Chillón

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