Paper explains WHY mycotoxins INHALED in indoor air are SO much more damaging to the brain.

[Guest guest]

Please read this paper, its the missing link....

Scroll down for the abstract and a link to the full text in PDF format

(with graphics, etc.)

BMC Neurosci. 2008 Dec 10;9 Suppl 3:S5.

Click here to read

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed & pubmedid=1909100\

2

Intranasal delivery bypasses the blood-brain barrier to target

therapeutic agents to the central nervous system and treat

neurodegenerative disease.

Hanson LR, Frey WH 2nd.

Alzheimer's Research Center at Regions Hospital, HealthPartners

Research Foundation, 640 Street, St, , MN 55101, USA.

PMID: 19091002 [PubMed - in process]

PMCID: PMC2604883

BMC Neurosci. 2008; 9(Suppl 3): S5.

Published online 2008 December 10. doi: 10.1186/1471-2202-9-S3-S5.

PMCID: PMC2604883

Copyright © 2008 Hanson and Frey; licensee BioMed Central Ltd.

Intranasal delivery bypasses the blood-brain barrier to target

therapeutic agents to the central nervous system and treat

neurodegenerative disease

Leah R Hanson1 and H Frey, II1,2

1Alzheimer's Research Center at Regions Hospital, HealthPartners

Research Foundation, 640 Street, St. , Minnesota 55101,

USA

2Department of Pharmaceutics, University of Minnesota, 308 Harvard

Street S.E., Minneapolis, Minnesota 55455, USA

Corresponding author.

H Frey, II: alzheimr@...

Supplement

Proceedings of the 2007 and 2008 Drug Discovery for Neurodegeneration Conference

Fillit and Antony Horton

The conference and the publication of these proceedings were supported

by a conference grant: U13-AG031125 from the National Institute of

Aging and the National Institute for Neurological Disorders and

Stroke. Additional support was provided by CoMentis, Inc; Pfizer,

Inc.; Biogen Idec and Boehringer Ingelheim Pharmaceuticals, Inc.

http://www.biomedcentral.com/content/pdf/1471-2202-9-S3-info.pdf

Conference

2007 and 2008 Drug Discovery for Neurodegeneration Conference

Washington DC USA 4–5 February 2008

New York, USA. 5-6 February 2007

This is an open access article distributed under the terms of the

Creative Commons Attribution License

(http://creativecommons.org/licenses/by/2.0), which permits

unrestricted use, distribution, and reproduction in any medium,

provided the original work is properly cited.

Abstract

Intranasal delivery provides a practical, non-invasive method of

bypassing the blood-brain barrier (BBB) to deliver therapeutic agents

to the brain and spinal cord. This technology allows drugs that do not

cross the BBB to be delivered to the central nervous system within

minutes. It also directly delivers drugs that do cross the BBB to the

brain, eliminating the need for systemic administration and its

potential side effects. This is possible because of the unique

connections that the olfactory and trigeminal nerves provide between

the brain and external environment. Intranasal delivery does not

necessarily require any modification to therapeutic agents. A wide

variety of therapeutics, including both small molecules and

macromolecules, can be targeted to the olfactory system and connected

memory areas affected by Alzheimer's disease. Using the intranasal

delivery system, researchers have reversed neurodegeneration and

rescued memory in a transgenic mouse model of Alzheimer's disease.

Intranasal insulin-like growth factor-I, deferoxamine, and

erythropoietin have been shown to protect the brain against stroke in

animal models. Intranasal delivery has been used to target the

neuroprotective peptide NAP to the brain to treat neurodegeneration.

Intranasal fibroblast growth factor-2 and epidermal growth factor have

been shown to stimulate neurogenesis in adult animals. Intranasal

insulin improves memory, attention, and functioning in patients with

Alzheimer's disease or mild cognitive impairment, and even improves

memory and mood in normal adult humans. This new method of delivery

can revolutionize the treatment of Alzheimer's disease, stroke, and

other brain disorders.

Introduction

The use of intranasal (IN) administration to target therapeutics to

the central nervous system (CNS) has many benefits in the treatment of

neurologic disorders. The blood-brain barrier (BBB) restricts the use

of numerous therapeutic agents that have been developed to treat

memory loss and neurodegeneration because it limits CNS penetration,

depending on drug size or charge.

Although invasive methods of administration (for instance

intracerebroventricular) have been used to overcome the BBB, these

methods are not practical for use in humans for several reasons,

including convenience, safety, and cost. Direct delivery of

therapeutics from the nasal cavity into the CNS (IN delivery) bypasses

the BBB and provides an alternative to invasive methods of drug

administration [1,2]. Noninvasive IN delivery targets therapeutics to

the CNS, reducing systemic exposure and side effects; this can be

advantageous for delivery of many CNS therapeutics, including those

that can cross the BBB upon systemic administration. CNS therapeutics

do not necessarily need to be modified for IN delivery, and delivery

of therapeutics to the CNS is rapid, occurring within minutes. The IN

delivery method was first developed by Frey in 1989 [3] for targeting

neurotrophic factors (for example, nerve growth factor [NGF] and

fibroblast growth factor-2) to the CNS.

Olfactory and trigeminal pathways

Intranasally administered therapeutics reach the CNS via the olfactory

and trigeminal neural pathways. Both the olfactory and trigeminal

nerves innervate the nasal cavity, providing a direct connection with

the CNS. Direct delivery of therapeutics from the nose to the brain

was initially attributed to the olfactory pathway [3-6]. More

recently, the contribution made by the trigeminal pathway to IN

delivery to the CNS has also been recognized, especially to caudal

brain regions and the spinal cord [7,8]. Extracellular delivery,

rather than axonal transport, is strongly indicated by the short time

frame (≤ 10 minutes) observed for IN therapeutics to reach the brain

from the nasal mucosa. Possible mechanisms of transport may involve

bulk flow and diffusion within perineuronal channels, perivascular

spaces, or lymphatic channels directly connected to brain tissue or

cerebrospinal fluid [9].

Intranasal delivery targets therapeutics to the central nervous system

IN delivery has been used to target a wide variety of therapeutics to

the CNS. For example, the following classes of therapeutics have

successfully been intranasally delivered to the CNS: neurotrophins

(NGF [5] and insulin-like growth factor [iGF]-1 [7]); neuropeptides

(hypocretin-1 [10] and exendin [11]); cytokines (interferon β-1b [8]

and erythropoietin [12]); polynucleotides (DNA plasmids [13] and genes

[14]); and small molecules (chemotherapeutics [15] and carbamazepine

[16]). IN delivery works best for potent therapeutics that are active

in the nanomolar range [1]. Even therapeutics that are substrates for

the P-glycoprotein efflux transporter, which is known to operate in

the nasal epithelium, have been reported to reach the CNS in effective

concentrations [17].

Intranasal neurotrophins for the treatment of neurodegeneration

Although the ability of neurotrophins to protect and promote the

growth of new neurons makes them desirable candidates for the

treatment of neurodegenerative disease, the inability of neurotrophins

to cross the BBB efficiently, and the impracticality of invasive

injection methods, have prevented their use. Growing evidence suggests

that IN administration of neurotrophins provides a noninvasive way to

target neurotrophins to the CNS to treat neurodegeneration. In a mouse

model of Alzheimer's disease, IN administered NGF both reduced

neurodegeneration and improved performance in memory tasks [18,19]. In

a rat model of stroke, IN IGF-I reduced brain damage and neurologic

deficits [20]. In addition, cerebral neurogenesis was induced in the

subventricular zone of adult mice after IN administration of FGF-2

[21]. IN activity dependent neurotrophic factor, as well as its active

peptide fragment NAP, have been shown to reduce neurodegeneration, tau

pathology, amyloid accumulation, and memory loss in mouse models of

Alzheimer's disease [22-25]. IN NAP is now being tested in phase II

clinical trials as a potential treatment for Alzheimer's disease and

mild cognitive impairment.

Memory is improved by intranasal insulin treatment

IN insulin improves memory in normal adults and patients with

Alzheimer's disease without altering blood glucose. Energy metabolism

in the CNS is dependent upon glucose uptake and is regulated by

insulin in key brain regions. It has long been known that glucose

uptake and utilization are deficient in patients with Alzheimer's

disease [26]. Recently, the gene expression levels of insulin, IGF-1,

and their receptors were shown to be markedly reduced in the brains of

patients with Alzheimer's disease [27]. Consequently, ability to

deliver insulin to the CNS without altering blood glucose could

provide an effective means to improve glucose uptake and utilization,

and reduce cognitive deficits in patients with memory disorders.

Using the IN delivery method to target insulin to the CNS originally

developed by Frey [28], Born and coworkers [29] demonstrated that

cerebrospinal fluid insulin levels significantly increased after

treatment of normal adults with insulin, with no change in blood

levels of insulin. In normal adults, IN treatment with insulin for 8

weeks improved memory (delayed recall of words) and mood at doses that

did not alter blood levels of insulin or glucose [30]. In addition, IN

administration of a rapidly acting form of insulin that forms hexamers

and is more rapidly absorbed, insulin aspart, improved memory in

normal adults significantly more than did regular insulin [31]. In

Alzheimer's patients, a single IN treatment acutely improved verbal

memory (total story recall and total word list recall) at doses that

did not alter blood levels of insulin or glucose [32]. The benefit of

IN insulin treatment was seen primarily for Alzheimer's patients

without the apolipoprotein E ε4 allele. Longer treatment with IN

insulin (21 days) enhanced memory, attention, and functioning compared

with placebo in patients with either early stage Alzheimer's disease

or mild cognitive impairment [33,34].

Top

Conclusion

IN delivery is a noninvasive method that bypasses the BBB and targets

drugs to the CNS, reducing systemic exposure and side effects. This

novel method has already been used successfully to improve memory in

both normal adults and patients with Alzheimer's disease. IN delivery

could revolutionize the way we treat Alzheimer's disease and other

neurodegenerative disorders.

Top

List of abbreviations used

BBB: blood-brain barrier; CNS: central nervous system; IN: intranasal;

NGF: nerve growth factor.

Top

Competing interests

WHF holds intellectual property related to IN delivery of

therapeutics. LRH and WHF are inventors on patents related to IN

delivery of therapeutics.

Acknowledgements

This article has been published as part of BMC Neuroscience Volume 9

Supplement 3, 2008: Proceedings of the 2007 and 2008 Drug Discovery

for Neurodegeneration Conference. The full contents of the supplement

are available online at

http://www.biomedcentral.com/1471-2202/9?issue=S3.

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________________________________

Articles from BMC Neuroscience are provided here courtesy of

BioMed Central

[Guest guest]

Live, I am not following you on this one. Please explain to me what I am missing

as this pertains to us or is a missing piece. I know I am missing something but

help me out here. Thanks

Chris...

    

 

 

 

 

 

 

 

[Guest guest]

Thanks Live,exactly, and this is the part most people dont get.

just how easily chemicals and toxins can reach our brain and affect

us. this is so important, and it's very obvious that the nose is the

most suspectable route even at low doses of exposure where chemical's

still make it past the mucus system and into the very thin layers of

tissue to the nerves and even the blood vessels in the nose and

through the nasal roof to the olfactory bulbs and brain. it's obvious

that it's known now the route chemicals cause alztimers and it's just

insane that there could still be any debate about how exposure to

mycotoxins and voc's can affect the brain and cause nerve damage, and

plus other contaminants causeing spinal/CSF infections or

inflamationS AND WHEN A DOCTOR DOES NOT DEAL WITH THIS, HOW IT CAN

CAUSE BRAIN SWELLING AND TBI AND EVEN CSF TO DAMAGE AND LEAK OUT OF

YOUR EARS AND NOSE.

--- In , LiveSimply <quackadillian@...>

wrote:

>

> Please read this paper, its the missing link....

>

[Guest guest]

Things you inhale in air, through your nose, impact on the convoluted

wet folds of the sinus tissue and go into the blood where they are

rapidly carried DIRECTLY INTO THE BRAIN, bypassing the blood brain

barrier, bypassing the stomach, the immune system's defenses,

bypassing the gut, completely avoiding cholestyramine being able to

bind them and all the rest..

The World Heath Organization in *1999* referenced the animal studies

that ACOEM and AAAAI had a fiduciary duty to mention too, but

deliberately ignored..

The military and other researchers have consistantly found that many

mycotoxins are far more toxic when:

*inhaled

or

*injected directly into the brain,

than

when

*eaten

or

*absorbed through the skin..

Given that people have repeatedly begged the medical community to

recognize that mold effects the brain, and said again and again that

it changes them- permanently, as brain injuries are wont to do,

SOMETHING IS VERY WRONG THAT THEY IGNORE THIS RESEARCH

JUST BECAUSE IT SHOWS HOW MOLD TOXINS REACH THE BRAIN

BYPASSING THE BLOOD BRAIN BARRIER AND THE LIVER..

Now, the drug industry is busy comerciallizing the intranasal route

through the blood brain barrier..

Tons of research is being done on it. Some of these drugs are even mycotoxins..

It couldn't be clearer.. Something is very wrong.

On Thu, Jan 15, 2009 at 3:22 AM, <unitedstatesvet@...> wrote:

> Live, I am not following you on this one. Please explain to me what I am

> missing as this pertains to us or is a missing piece. I know I am missing

> something but help me out here. Thanks

> Chris...

>

>

>

>

>

>

>

>

>

>

>

[Guest guest]

I've been posting and trying to get people to realize this for a long

time. I had alot of damage in this area so it made it very obvious to

me that even at lower dose exposures what people complain about as a

stuffy nose, bad taste in the mouth, and brain fog,ect. this is whats

happening and believe me it's nothing to take lightly. with lower

dose exposures you might not realize whats really happening yp in

your nose. I have doctors notes of complaining about the bad taste

and stuffy nose from my first home early on. the brain effects were

so gradual I didn't realize I was haveing any and it was probably the

brain effects that kept me from realizeing much of anything. but the

nerve effects were immedete and strong and so was the spinal

infection/inflamation. and whar was draining down my throat to my

stonach was no good either. this was so different from the second

home that was so bed when I moved in it was a nightmare to be there

as long as I was. and only that long because I had the windoes open

the first 2 1/2 months. I dont know how else to make people realize

that this route from the nose to the brain is so important when they

haven't had their exposure cause severe damage in that area to the

point that it's so obvious that you actually research it and dig for

hours to find what little info. is out there. but there is some and

I've posted here. one was about feed lot contamination afecting

neighbors that went into some detail about the damage to the

olfactory and sinus area. this is why I preach alot about washing the

sinuses !!

--- In , LiveSimply <quackadillian@...>

wrote:

>

> Things you inhale in air, through your nose, impact on the

convoluted

> wet folds of the sinus tissue and go into the blood

[Guest guest]

Well, Jeanine,

this is one situation in which you are 100% right.

Me too. You and me both.

Maybe someday the deniers will stop trying so hard to ignore the obvious.

On Fri, Jan 16, 2009 at 12:43 PM, who <jeaninem660@...> wrote:

> I've been posting and trying to get people to realize this for a long

> time. I had alot of damage in this area so it made it very obvious to

> me ...

Anybody who doubts the medical potency of inhalational exposure only

needs to go read the Bulletin of the World Heath Organization, 1999, vol 77(9)

pg 759

There it is.. *40 times* more toxic through the nose..

[Guest guest]

Excuse me, one of many, you just think you have to say it's so before

it offically is. thanks for the quick reminder of why I quit posting.

--- In , LiveSimply <quackadillian@...>

wrote:

>

> Well, Jeanine,

>

> this is one situation in which you are 100% right.

>

> Me too. You and me both.

[Guest guest]

Here's the link for the article.

http://www.who.int/docstore/bulletin/pdf/issue9/bu0024.pdf

________________________________

From: LiveSimply <quackadillian@...>

obvious.

Anybody who doubts the medical potency of inhalational exposure only

needs to go read the Bulletin of the World Heath Organization, 1999, vol 77(9)

pg 759

There it is.. *40 times* more toxic through the nose..