RE: biotech/trials-

[Guest guest]

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From: <thecolemans4@...>

>I wanted to ask what that means to us w/ the biotech co licensing the

>rights... does that restrict >us from having access?

No, a private company has a greater incentive to get them on the market.

Since our regulatory system has so many problems (congress has considered

new regulators to oversee the regulators) I'd feel better if I knew Canadian

regulators were doing some oversight.

>Were there some trials in CFS that were in later stages that were going

>well?

The major focus has been Alzheimer's and the trials seem to be going very

well. I think there's some new research I haven't posted. I'll go ahead

and post those for you. Below is some of the older info, the first one is

from when it became available for licensing.

Cheryl

Use of Activity Dependent Neurotrophic Factor Derived Peptides for Enhancing

Learning and Memory

DE Brenneman and Spong (NICHD), Ilana Gozes (Tel Aviv University)

Serial No/Ref: No.: E-147-96/8 (PCT) filed May 31, 2001 which claims

priority to 60/267,805 (E-147-96/6) filed February 8, 2001 and 60/208,944

(E-147-96/5) filed May 31, 2000.

These application(s) disclose the use of ADNF polypeptides, ADNF and ADNF

III/ADNP or the ADNF derived peptides SAL (SALLRSIPA) and NAP (NAPVSIPQ) to

improve learning and memory. The peptides SAL and NAP are preferred because

of their ability to cross the blood-brain barrier and for their ease of

synthesis. The peptides, when given alone or in combination, either in utero

or post-natally, improve performance related to learning and memory.

Combinations of NAP and SAL are preferred for prenatal administration. NAP

alone is preferred for post-natal administration. The ability to improve

learning and memory when given in utero makes them attractive as candidates

for the development of therapeutics for prevention or treatment of Down's

Syndrome or Fragile X syndrome or other conditions associated with mental

retardation. The ability to improve performance related to learning and

memory in adults makes them attractive candidates for the development of

therapeutics for Alzheimer's disease as well as Down's Syndrome or other

conditions associated with mental retardation.

This work has been published, in part, at Gozes I, et al.

``Activity-dependent neurotrophic factor: intranasal administration of

femtomolar-acting peptides improve performance in a water maze'' J Pharmacol

Exp Ther, 293(3):1091-8 (Jun 2000).

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[ activity-dependent neurotrophic factor ] This protein is secreted into the

conditioned medium of astroglial cells in the presence of the neuropeptide

VIP . At femtomolar concentrations it protects neurons from cell death by

apoptosis associated with electrical blockade by tetrodotoxin. ADNF also

protects neurons against apoptosis induced by amyloid beta-peptide,

N-methyl-D-aspartate, tetrodotoxin, HIV envelope coat protein gp120 ,

oxidative stress, and trophic factor withdrawal (Brenneman et al; Glazner et

al). Some peptides derived from ADNF show the same activities as the parent

protein. ADNF-14 is a peptide (VLGGGSALLRSIPA) derived from ADNF. ADNF-9 (

SALLRSIPA) is a bioactive and more potent peptide with a broader effective

concentration range (10**-16 to 10**-13 M than ADNF or ADNF-14 (Brenneman et

al). For a structurally related peptide with similar activities see also:

ADNP .

ADNF-9 has been shown to increase expression of transcription factor

NF-kappa-B and to lose its anti-apoptotic activity when NF-kappa-B

activation is blocked (Glazner et al). ADNF-9 has been shown to increase the

expression of heat shock protein 60 (hsp60) in rat cerebral cortical

cultures, which is reduced by treatment of cells with beta-amyloid peptide

(Zamostiano et al).

Antisera against ADNF decrease neuronal survival. The effect of antisera is

blocked by cotreatment with ADNF or bioactive peptides derived from ADNF.

These effects of ADNF are not mimicked by IGF-1 , PDGF , NGF , EGF , CNTF ,

or NT-3 . ( Gozes et al).

ADNF has been shown to act directly on neurons and to promote glutamate

responses and morphological development. It causes the secretion of NT-3 ,

which, together with ADNF, regulates glutamate receptors (Blondel et al).

ADNF has been shown to interrupt excitotoxic neurodegenerative cascades in

neurons lacking expression of the presenilin-1 gene, which is causally

linked to many cases of early-onset inherited Alzheimer's disease (Guo et

al).

[ activity-dependent neuroprotective protein ] This protein of 828 amino

acids has been identified as a mediator of neuronal survival induced by

various stimuli causing cell death by apoptosis . Expression of ADNP is

upregulated in astrocytes by VIP . ADNP is widely distributed in the mouse

hippocampus, cerebellum, and cerebral cortex (Gozes et al).

NAP ( NAPVSIPQ) is a peptide derived from ADNP. NAPVSIPQ shares structural

and functional similarities with ADNF-9 and has the same neuroprotective

activities at a concentration range of 10**-18 to 10**-10 M . NAPVSIPQ acts

directly on neurons in culture and protexts the cells against various

neurotoxic insults (Zemlyak et al; Offen et al). In a mouse model of closed

head injury injection of NAPVSIPQ reduces edema formation, and mortality. It

causes significant brain-tissue recovery and facilitates neurobehavioral

recovery. NAPVSIPQ treatment decreases TNF-alpha levels in the injured brain

and has been shown to protect PC12 pheochromocytoma cells against apoptosis

induced by TNF-alpha (Beni-Adani et al). NAPVSIPQ also prevents fetal death

and growth restriction associated with prenatal alcohol exposure (Spong et

al).