Discovery of possible Alzheimer's treatment - Dr. Jerold Chun

Jerold Chun, M.D., Ph.D., professor and senior vice president of Neuroscience Drug Discovery at Sanford Burnham Prebys Medical Discovery Institute, describes his latest research published in Nature—which provides hope there is a near-term medicine that could treat Alzheimer's disease.

In the study, Chun and his team identified never-before-seen gene recombination, or "mixing and matching" of DNA, in the brain.

Their work focused on the Alzheimer’s-linked gene, APP, and revealed it is recombined by using the same type of enzyme found in HIV.

This finding indicates existing FDA-approved antiretroviral therapies for HIV that block reverse transcriptase might also be able to halt the recombination process—and could be explored as a new treatment for Alzheimer’s disease.

There is no medical evidence that HIV or AIDS causes Alzheimer’s disease.

Read the press release: http://bit.ly/2OT0Qw6

See the science behind the discovery:    • A potential near-term treatment for A...  

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Full transcript:

Our research provides hope that we have a near-term medicine to treat Alzheimer's disease.

“Discovery of Possible New Alzheimer’s Treatment.” (On Screen Title)

My name is Jerold Chun. I'm a professor and senior vice president for neuroscience drug discovery here at Sanford Burnham Prebys Medical Discovery Institute.

Alzheimer's disease is the most common cause of dementia in the U.S., affecting some 5.7 million people and that number is going to be going up, very rapidly in the coming decades. Alzheimer's disease is devastating to the individual.

It falls into two basic categories, those that are inherited and those that are not. The inherited forms account for perhaps just one percent. That raises the question of what's going on in that other 99% of cases?

What one has been taught in school for many, many years, is that every single cell in your body has an identical blueprint, identical genome that started from that initial fertilization step.

What we found is that in (in fact) they change, and they change the very blueprint of a given cell. That is one of the core implications of the study that we’ve just reported. Scientists referred to this as gene recombination.

Gene recombination is a natural process. And in fact it is the basis of our immune system. Gene recombination is a process where a contiguous, a stretch of DNA is cut, and then another piece can be brought to that cut piece to form a new DNA sequence. This is very similar to bringing together pieces of film. Splice it together and that would form your new movie or your new edited movie

The key finding from this work is that gene recombination occurs within the brain. It involves this gene referred to as APP or amyloid precursor protein that then can form the amyloid plaques, thought to be a major cause of Alzheimer's disease. Alzheimer's is a disease where recombination goes awry.

Identifying gene recombination also led to an understanding of some of the very basic mechanisms that produce the recombination. There's an enzyme that we identified that is well known to many, many, many biologists called reverse transcriptase. This enzyme is quite famous because it was the first to overturn the so-called ‘Central Dogma’ going from DNA to RNA to protein. The reverse transcriptase will take an RNA and turn it into a DNA, so it goes backwards. And why is that interesting?

Well it suggests that you might be able to interrupt that enzyme's activity and then actually bring about some therapeutic advantages. HIV is treated in part by inhibitors of this reverse transcriptase.

We then proceeded to look through the literature at individuals that were in that ‘65ish’ range or older of which there are approximately 100,000 taking these reverse transcriptase therapies for many, many years. We would have predicted there should've been 2, 3,000 people with Alzheimer's disease in that age group. And what we found in the literature was at this point there had only been one; one report of Alzheimer's disease in that HIV population.

The exciting possibility is that we could take already FDA-approved agents that have been in humans in some cases for decades and test this, test them, in actual Alzheimer's disease patients.

It would be remarkable if it turns out that HIV, this, this terrible disease, gives rise to the first effective treatments for Alzheimer's disease.