Antiviral drugs may slow Alzheimer's progression - acycolovir inhibits amyoid

October 17, 2011

Antiviral drugs may slow Alzheimer's progression

http://www.manchester.ac.uk/aboutus/news/display/?id=7543

Antiviral drugs used to target the herpes virus could be effective at

slowing the progression of Alzheimer's disease (AD), a new study shows.

The University of Manchester scientists have previously shown that the

herpes simplex virus type 1 (HSV1) is a risk factor for Alzheimer's when

it is present in the brains of people who have a specific genetic risk

to the disease.

AD is an incurable neurodegenerative condition affecting about 18

million people worldwide. The causes of the disease or of the abnormal

protein structures seen in AD brains – amyloid plaques and

neurofibrillary tangles – are completely unknown.

The Manchester team has established that the herpes virus causes

accumulation of two key AD proteins – â-amyloid (Aâ) and

abnormally phosphorylated tau (P-tau) – known to be the main

components of plaques and tangles respectively. Both proteins are

thought by many scientists to be involved in the development of the

disease.

" We have found that the viral DNA in AD brains is very specifically

located within amyloid plaques, " said Professor Ruth Itzhaki, who led

the team in the University's Faculty of Life Sciences. " This, together

with the production of amyloid that the virus induces, suggests that

HSV1 is a cause of toxic amyloid products and of plaques.

" Our results suggest that HSV1, together with the host genetic factor,

is a major risk for AD, and that antiviral agents might be used for

treating patients to slow disease progression. "

Currently available antiviral agents act by targeting replication of

HSV1 DNA, and so the researchers considered that they might be

successful in treating AD only if the accumulation of â-amyloid and

P-tau accumulation caused by the virus occurs at or after the stage at

which viral DNA replication occurs.

" If these proteins are produced independently of HSV1 replication,

antivirals might not be effective, " said Professor Itzhaki. " We

investigated this and found that treatment of HSV1-infected cells with

acyclovir, the most commonly used antiviral agent, and also with two

other antivirals, did indeed decrease the accumulation of â-amyloid

and P-tau, as well as decreasing HSV1 replication as we would expect.

" This is the first study investigating antiviral effects on AD-like

changes and we conclude that since antiviral agents reduce greatly

â-amyloid and P-tau levels in HSV1-infected cells, they would be

suitable for treating Alzheimer's disease. The great advantage over

current AD therapies is that acyclovir would target only the virus, not

the host cell or normal uninfected cells. Further, these agents are very

safe and are relatively inexpensive.

" Also, by targeting a cause of Alzheimer's disease, other viral damage,

besides â-amyloid and P-tau, which might be involved in the disease's

pathogenesis, would also be inhibited.

" The next stage of our research – subject to funding – will

focus on finding the most suitable antiviral agent – or combination

of two agents that operate via different mechanisms – for use as

treatment. We then need to investigate the way in which the virus and

the genetic risk factor interact to cause the disease, as that might

lead to further novel treatments.

" Eventually, we hope to begin clinical trials in humans but this is

still some way off yet and again will require new funding. "

The study, carried out with Dr Wozniak and other colleagues in

the Faculty of Life Sciences, is published in the Public Library of

Science (PLoS) One journal.

October 18, 2011

This is interesting but there must be some other thing going on with respect to the deterioration of the immune function.Maybe it is oxidative stress (due to aging and associated reasons in this case) decreasing the immune function leading to chronic viral state.Is virus just co-morbid or the underlying trigger?To: mb12valtrex Sent: Monday, October 17, 2011 3:26 PMSubject: Antiviral drugs may slow Alzheimer's progression - acycolovir inhibits amyoid

Antiviral drugs may slow Alzheimer's progression

http://www.manchester.ac.uk/aboutus/news/display/?id=7543

Antiviral drugs used to target the herpes virus could be effective at

slowing the progression of Alzheimer's disease (AD), a new study shows.

The University of Manchester scientists have previously shown that the

herpes simplex virus type 1 (HSV1) is a risk factor for Alzheimer's when

it is present in the brains of people who have a specific genetic risk

to the disease.

AD is an incurable neurodegenerative condition affecting about 18

million people worldwide. The causes of the disease or of the abnormal

protein structures seen in AD brains â€“ amyloid plaques and

neurofibrillary tangles â€“ are completely unknown.

The Manchester team has established that the herpes virus causes

accumulation of two key AD proteins â€“ Ã¢-amyloid (AÃ¢) and

abnormally phosphorylated tau (P-tau) â€“ known to be the main

components of plaques and tangles respectively. Both proteins are

thought by many scientists to be involved in the development of the

disease.

"We have found that the viral DNA in AD brains is very specifically

located within amyloid plaques," said Professor Ruth Itzhaki, who led

the team in the University's Faculty of Life Sciences. "This, together

with the production of amyloid that the virus induces, suggests that

HSV1 is a cause of toxic amyloid products and of plaques.

"Our results suggest that HSV1, together with the host genetic factor,

is a major risk for AD, and that antiviral agents might be used for

treating patients to slow disease progression."

Currently available antiviral agents act by targeting replication of

HSV1 DNA, and so the researchers considered that they might be

successful in treating AD only if the accumulation of Ã¢-amyloid and

P-tau accumulation caused by the virus occurs at or after the stage at

which viral DNA replication occurs.

"If these proteins are produced independently of HSV1 replication,

antivirals might not be effective," said Professor Itzhaki. "We

investigated this and found that treatment of HSV1-infected cells with

acyclovir, the most commonly used antiviral agent, and also with two

other antivirals, did indeed decrease the accumulation of Ã¢-amyloid

and P-tau, as well as decreasing HSV1 replication as we would expect.

"This is the first study investigating antiviral effects on AD-like

changes and we conclude that since antiviral agents reduce greatly

Ã¢-amyloid and P-tau levels in HSV1-infected cells, they would be

suitable for treating Alzheimer's disease. The great advantage over

current AD therapies is that acyclovir would target only the virus, not

the host cell or normal uninfected cells. Further, these agents are very

safe and are relatively inexpensive.

"Also, by targeting a cause of Alzheimer's disease, other viral damage,

besides Ã¢-amyloid and P-tau, which might be involved in the disease's

pathogenesis, would also be inhibited.

"The next stage of our research â€“ subject to funding â€“ will

focus on finding the most suitable antiviral agent â€“ or combination

of two agents that operate via different mechanisms â€“ for use as

treatment. We then need to investigate the way in which the virus and

the genetic risk factor interact to cause the disease, as that might

lead to further novel treatments.

"Eventually, we hope to begin clinical trials in humans but this is

still some way off yet and again will require new funding."

The study, carried out with Dr Wozniak and other colleagues in

the Faculty of Life Sciences, is published in the Public Library of

Science (PLoS) One journal.

October 18, 2011

That's an unfair question because you could simply turn around and ask what caused the increased oxidative stress? And then what caused *that*? It's a never-ending circle that we'll probably not be able to answer in our lifetimes, probably not our children's lifetimes. It's important to work on them but unless you plan to start entering the research game and answering those questions, we work with what we've got. We're getting pieces and we treat with what pieces we know until we know more. Like the saying goes: when we know better, we do better.If you're asking those questions, it's a good bet the researchers and scientists have already asked them themselves. (I don't mean to imply that parents shouldn't ask questions, discuss or debate, only that we understand that there are no answers to many of those questions - the best we've got are more questions.)

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