Can Thor’s dementia be prevented? blue light gene therapy

Chris Hemsworth, the Australian-born Hollywood star famous for the Marvel character ‘Thor’, recently announced that he would be taking a break from his activities for the time being to focus on treatment after discovering that he is genetically more likely to develop dementia. The gene he mentioned is ‘ApoE4’.

ApoE is a gene that contains information about the production of proteins involved in lipid metabolism. There are three types of variation in humans: ApoE2, ApoE3, and ApoE4. Having ApoE2 reduces the risk of Alzheimer’s disease, but having ApoE4 increases the chance. ApoE3, the most common, is known to be neutral. ApoE inherits one genotype from each parent, and the case of inheriting a pair of ApoE4 is very rare at 2%, but the risk of getting Alzheimer’s disease increases 8 to 10 times. Hemsworth said he took a genetic test while filming a documentary about life extension and discovered he was part of that 2%.

A new treatment, which injects the ApoE2 gene into the brains of people like Hemsworth to prevent them from developing Alzheimer’s disease, has had promising results in small clinical trials. Proteins from the extra gene were found in the cerebrospinal fluid of patients undergoing clinical trials, and brain levels of amyloid beta (Aβ) and tau protein, biomarkers of Alzheimer’s disease, were found to be reduced. This is what the New York Times (NYT) reported on the 2nd (local time) based on the preliminary results of American researchers published at a recent Alzheimer’s disease clinical trial meeting.

The clinical trial, funded by the non-profit organization ‘Alzheimer’s Drug Discovery Foundation (ADDF)’ and sponsored by ‘Lexio Therapeutics’, a bio-enterprise company founded by Weill Cornell Medical School professor Ronald Crystal (genetic medicine ), includes five. patients. Like Hemsworth, they inherited the ApoE2 gene from both parents and had the first stage of Alzheimer’s disease. Professor Sam Gandy from Mount Sinai Hospital in the United States, one of the research team, said that there is no cure in these cases, so they are “people who have no choice but to make a desperate attempt in desperate times. ” For five other patients, a higher dose of gene injection than in this clinical trial is performed, he added.

Professor Gandhi was one of three researchers at Rockefeller University in the United States who first conceived of this treatment 25 years ago. The other two were Professor Michael G. Capulet (neurosurgery) at Weill Cornell Medical School and Dr. Paul Greengard, who died in 2019 and won the 2000 Nobel Prize in Medicine and Physiology. He published the three essays in December 1996 on the idea that if the brain environment of a person with a pair of ApoE4s could be moved to resemble that of a person with one APOE4 and one APOE2, the risk of Alzheimer’s could be cut in half.

But at the time, technology could not support it, and the three were busy with other projects, explained Professor Capulet, who led the clinical trial. But now it is possible to use a harmless adeno-associated virus (AAV) as a vehicle to inject a copy of the ApoE2 gene into the spinal fluid and send it to the brain.

Experts who were not involved in the clinical trial welcomed the results. “This is a very stimulating and exciting approach,” said Eliza Maslia, director of neuroscience at the National Institute on Aging (NIA). Dr. Deborah L. Blacker, a geriatric psychiatrist at Massachusetts General Hospital, found that based on the most positive data, if a person who inherits one pair of ApoE4 mutations has a lifetime risk of 30% to 55% of Alzheimer’s, then the risk for those who inherit ApoE4 and ApoE2 is about 20% % to less than half.

It is not clear exactly how ApoE4 makes people more likely to develop Alzheimer’s disease, or why people with both variants do not develop the disease. However, there is growing expectation that this clinical trial will be the spark to slow or protect the onset of Alzheimer’s disease in high-risk groups like Hemsworth.

Harvard University geneticist Professor Robert C Green, who has been studying ApoE4, warned that the scale of the clinical trial was too small to draw such hasty conclusions, but gave a positive response saying he was “impressed” by the proof of concept ” treatment.