What can HIV drugs teach us about Alzheimer’s treatment?
- Alzheimer’s disease is the
most common form of dementia at a global level.
- Scientists say that more
therapy options are needed for the disease.
- Researchers from Sanford
Burnham Prebys Medical Discovery Institute in La Jolla, CA, believe common
HIV medications may offer potential treatment opportunities for
Alzheimer’s disease.
Researchers from Sanford Burnham Prebys Medical
Discovery Institute in La Jolla, CA, have recently conducted a study which
suggests that medications commonly used to treat HIV may
also offer potential treatment opportunities for Alzheimer’s disease.
Their study paper appears in the journal Pharmaceuticals.
“Alzheimer’s disease is the most common causeTrusted
Source of dementia in
the United States and worldwide, affecting [approximately] 7 million people in
the U.S. alone,” Jerold Chun, MD, PhD, professor in the Degenerative Diseases
Program at Sanford Burnham Prebys Medical Discovery Institute in La Jolla, CA,
and lead author of the study, told Medical News Today.
“In addition to those afflicted, families, society,
and our economy are severely impacted by Alzheimer’s disease,” Chun added.
According to him, “[currently] approved
therapies [for Alzheimer’s] have marginal benefit — [they] are
not cures nor truly disease-modifying — and can also negatively affect patient
health.“
“New treatment options that work better with less
health risk are needed,” said Chun.
What is reverse transcriptase, and what does it do?
Chun explained that his and his team’s study is based
on previous researchTrusted Source published
in 2018 that identified a reverse transcriptase-dependent phenomenon called “somatic gene
recombinationTrusted Source,” which affected genes
capable of promoting Alzheimer’s disease.
“Reverse transcriptase is a
famous protein — a protein that can do things is called an ‘enzyme’ and reverse
transcriptase is an enzyme — that can copy RNATrusted
Source — the stuff that encodes proteins in our cells —
back into DNA,
a ‘reverse’ process from the usual ‘Central Dogma’ of DNA-to-RNA-to-protein.”–
Jerold Chun, MD, PhD
“The reverse transcriptase was and is thought to be
part of our brain — i.e., endogenous vs. from an exogenous viral infection,” he
continued. “This [previous] discovery raised the possibility that blocking
reverse transcriptase might be helpful in treating Alzheimer’s disease.”
Chun said that reverse transcriptase was first
discoveredTrusted Source in RNA viruses in
1970.
“It turns out that our brain — and body — have their
own reverse transcriptases, which may go awry to promote Alzheimer’s disease
and likely other brain disorders,” he detailed.
“HIV — the virus that causes AIDS —
itself is an RNA virus that has its own reverse transcriptase. Medical science
and the pharmaceutical industry have discovered many drugs called reverse
transcriptase inhibitors that interrupt HIV’s life cycle, which has saved many
AIDS patients,“ Chun said.
“Some of these same drugs could also work on the
brain’s reverse transcriptases, which we examined observationally in the
current study in those aged survivors who had received reverse transcriptase
inhibitors,” he added.
HIV drugs tied to significant reduction in Alzheimer’s occurrence
For this study, Chun and his team analyzed medical
records from more than 225,000 people, with about 80,000 having HIV and over
the age of 60. More than 46,000 study participants had taken reverse
transcriptase inhibitors.
Upon
analysis, the researchers found that study participants who had exposure to
reverse transcriptase inhibitors had a statistically significant reduced
occurrence and frequency of Alzheimer’s disease.
“These results were expected,” Chun said. “In our 2018
report, we searched for cases of HIV-positive persons with Alzheimer’s disease
and really could not find robust evidence of them, despite an expectation a
decade earlier by some in the HIV field, of an avalanche of Alzheimer’s disease
patients coming from this group.”
“Instead, [the] first apparent case was only
seen in 2016,” he continued. “We, therefore, pursued an in-depth
look by assessing tens of thousands of medical records of appropriate patients
and controls, resulting in the current report that identified beneficial
effects of reverse transcriptase inhibitor exposure in reducing Alzheimer’s disease.”
Some questions about how HIV drugs work for brain health
Chun also cautioned that more research is still needed
to examine the medicine and science of reverse transcriptases in Alzheimer’s
disease and other brain diseases:
“Prospective clinical trials
using reverse transcriptase inhibitors to reduce Alzheimer’s disease are
warranted in light of our study and the accumulating scientific literature, and
questions remain on when such drugs could work best in Alzheimer’s disease, on
whether there are certain Alzheimer’s disease sub-populations who could most
benefit, and whether certain drugs work better than others, which we believe is
the case.”
He explained that some questions we need to ask are:
“Scientifically, what is the source of endogenous [brain] reverse
transcriptases; what cells use it normally and what does it do there; and
how/where/when might it go awry?”
“Knowing this could enable the development of better
Alzheimer’s disease therapeutics, as well as extensions into other brain
diseases,” Chun noted.
“Finally, appropriate reverse transcriptase inhibitors
are already FDA-approved for treating HIV — and hepatitis B —
meaning that they could be prescribed to appropriate Alzheimer’s disease
patients now, as clinical trials that take many years are pursued. This may be
especially helpful in countries that use generic drugs since a number of
reverse transcriptase inhibitors are generic, towards helping Alzheimer’s
disease patients and their families,” the researcher suggested.
HIV drugs for Alzheimer’s: What are the mechanisms at play?
After reviewing this research, Karen D.
Sullivan, PhD, ABPP, a board-certified neuropsychologist, owner of I
CARE FOR YOUR BRAIN, and Reid Healthcare Transformation Fellow at FirstHealth
of the Carolinas in Pinehurst, NC, told MNT she found it to
be an intriguing and impressive study.
“With a
difference of 2.46 Alzheimer’s disease diagnoses per 1,000 persons among
HIV-positive individuals taking reverse transcriptase inhibitors versus 6.15
for the general population, there is clearly an effect of this compound,”
Sullivan noted.
“Our current treatment options for Alzheimer’s disease
only reduce decline to a modest degree with no prevention or reversal possible.
We need to invest in novel approaches, like this one, to find the next
generation of options,” she continued.
MNT also
spoke with Manisha Parulekar, MD, director of the Division of Geriatrics
at Hackensack University Medical Center, and co-director of the Center for
Memory Loss and Brain Health and associate professor at Hackensack Meridian
School of Medicine in New Jersey, about this study.
“Studies have shown elevated levels of reverse
transcriptase activity in the brains of individuals with Alzheimer’s disease
compared to healthy individuals, suggesting a possible association,” Parulekar
said.
“Few studies have also
explored possible correlation with tau proteinTrusted
Source and inflammation. Reverse transcriptase is an
enzyme that plays a complex and not completely understood role in Alzheimer’s
disease. While its exact contribution remains under investigation, several
studies, including this new study, suggest a potential link between reverse
transcriptase activity and the development of Alzheimer’s disease.”– Manisha
Parulekar, MD
“We do need to establish [a] better understanding of
the correlation of reverse transcriptase and Alzheimer’s disease pathology,”
she added. “This will allow us to get to the next steps of effective treatment
options.”
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