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Cancer vaccine; gene therapy for sight loss; fecal transplant to reverse aging

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Cancer vaccine; gene therapy for sight loss; fecal transplant to reverse aging

This is a recurring column on early-stage research in animals or other laboratory models that has not yet entered the clinic but could have implications for future research and development of human medicines.

A vaccine to prevent cancer

An experimental vaccine has shown promise for treating and preventing cancer in mice after researchers targeted a gene called KRAS that is involved in the development of the disease in the lung, bowels and pancreas.

Researchers from the Francis Crick Institute in London created a set of vaccines that can stimulate an immune response toward the most common KRAS mutations. Led by Rachel Ambler, scientists tested the vaccine on mice that already had lung tumors as well as those that were induced to grow them. They found that 65% of the vaccinated mice were alive after 75 days, compared with 15% who did not receive the jab. Of the mice treated to induce tumors, 40% of those vaccinated remained tumor-free after 150 days, compared with 5%of the unvaccinated mice. In all, vaccination delayed appearance of tumors by an average of 40 days.

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Researchers assessed the effects of a vaccine on cancer in mice
Source: Pixabay

"Previous trials of cancer vaccines have failed because they have not been able to create a strong enough response from the immune system to find and destroy cancer cells," said Ambler. "This research still has a long way to go before it could help prevent and treat cancer in people, but our results suggest that the design of this vaccine has created a strong response in mice with very few side effects."

Researchers from the same Crick team also discovered a new way to spot and treat aggressive forms of lung cancer that can evade the body's immune system. Using mice with cancers with similar KRAS activity, the scientists lowered levels of adenosine a chemical that dampens the body's immune response by administering AstraZeneca PLC's oleclumab, as well as existing cancer drugs that help the immune system fight cancer and improve survival.

"Together these results suggest it could eventually be possible to identify patients who have this aggressive type of lung cancer and use a combination of drugs to support their immune system and successfully treat their tumors," said co-study lead Phil East, deputy head of bioinformatics at the Francis Crick Institute.

Both studies were presented Oct. 23 at the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.

Gene therapy for vision loss

Scientists from Trinity College Dublin have developed a new gene therapy approach that offers promise in treating dominant optic atrophy, or DOA, which leads to a progressive loss of vision.

Published Nov. 26 in the journal Frontiers in Neuroscience, the study looked at a gene called OPA1, which provides instructions for making a protein pivotal for maintaining proper function in mitochondria the energy producers in cells. Led by Daniel Maloney and Jane Farrar from Trinity’s School of Genetics and Microbiology, researchers developed a new gene therapy that they hope may be effective in people.

"We used a clever lab technique that allows scientists to provide a specific gene to cells that need it using specially engineered non-harmful viruses," said Maloney. "This allowed us to directly alter the functioning of the mitochondria in the cells we treated, boosting their ability to produce energy. which in turn helps protect them from cell damage."

Broader neurological disorders associated with aging, including Alzheimer's and Parkinson's disease, are also affected by mitochondrial dysfunction, the researchers pointed out.

"Excitingly, our results demonstrate that this OPA1-based gene therapy can potentially provide benefit for diseases like DOA, which are due to OPA1 mutations, and also possibly for a wider array of diseases involving mitochondrial dysfunction."

Feces offers clue to halting cognitive decline

New research from the University of East Anglia and the Quadram Institute in the U.K., as well as the University of Florence in Italy, has raised the question of whether fecal transplants could one day be used as a therapy to restore cognitive function in the elderly.

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Researchers said their work highlighted the importance of the gut-brain axis in aging
Source: Thinkstock

Published in the journal Microbiome, researchers performed fecal transplants from older to younger mice and then assessed the younger subjects for markers such as anxiety, exploratory behavior and memory. They found significant differences in the young mice's microbial profiles, with impaired spatial learning and memory, as well as alterations in the expression of proteins, and changes to cells in the hippocampus part of their brains responsible for learning and memory.

"In short, the young mice began to behave like older mice, in terms of their cognitive function," said David Vauzour from the University of Norwich Medical School.

Claudio Nicoletti, a professor at the University of Florence, said the research highlights the importance of the gut-brain axis in aging and provides a strong rationale to devise therapies aimed at restoring a youthful microbiota.

"While it remains to be seen whether transplantation from very young donors can restore cognitive function in aged recipients, the findings demonstrate that age-related shifts in the gut microbiome can alter components of the central nervous system," Nicoletti said.