Protein from milk of genetically altered goats

[Guest guest]

When I was going to school in Boston, I remember reading an article

about a strange building under construction in the area that was

nearing completion. People had been asking questions about it, and a

reporter investigated. I forget the details, but the building was a

new, multi-million dollar manufacturing plant for a biotech firm.

The plant was going to manufacture a protein (I think) that was

needed by a very small number of people in the world. I forget the

disease, but the people affected were unable to produce this protein,

and they would die without it. Tons of raw material went into one

end of the plant, and milligrams of product would come out of the

other end at an agonizingly slow rate. It was arguably the most

valuable substance on earth, the reporter had said.

The irony was - it was projected that the plant would be obsoleted

shortly after it was started. Scientists were talking about

genetically altering goats and having them produce milk that would

contain the protein that was needed. The protein would almost become

a commodity. The research was very promising.

Of course, I drank an awful lot when I was in college in Boston, and

my memory may not be that accurate.

I did a quick Google search, and I found this:

http://www.nexiabiotech.com/en/01_tech/05.php

Has anyone else heard of this?

Could this be a way for making SMN protein?

[Guest guest]

Jonathon:

From this dumb guy's reading and thus far limited

understanding of SMA, the problem isn't necessarilly

just with the synthesis of SMN Protein. The problem

is associated with the lack of SMN Protein in an

area(s) where distributing the protein from an outside

source would be very difficult if not impossible. The

SMN Complex is a continual bodilly function whereby

SMN Protein is created and delivered throughout the

body - but only specifically dependent apparently in

Motor Neurons - in the Anterior Horn Cells.

Proteins of any sort can be created by using the

recipes per the DNA code - some combination of the 20

amino acids. Aside from difficulties associated the

potential size of the recipe, are additional issues of

how the protein is " folded " together - and the

resulting physical shape of the protein. However, I

don't think it would be all that difficult for SMN

protein to be produced externally - I woulndn't doubt

it if it has been done already.

SMN Delta 7 protein (that which is predominantly

produced by the SMN2 gene) - skips only a small

section of the normal SMN protein (as coded from exon

7 which has been excluded to due 1 single coding

mutation). Some researchers have been testing various

small molecules that attach to SMN Delta 7 and cause

it to appear more like regular SMN protein with some

initial in vitro success. In vitro, by the way,

simply refers to analysis in a lab dish or " in glass "

(had to look that up a ways back) - versus In Vivo

being in the body. But, aside from that, the SMN2

gene sometimes still does produce the proper protein -

about 10% of the time in just reads over the mutated

neucleotide and exon 7 is not excluded. Thus - the

current drug trials - to simply cause the SMN2 gene to

do this more often - that is, be more efficient in

producing SMN protein (vs SMN Delta 7 protein) by

causing it to exclude exon 7 less often, or by sheer

volume of cause the SMN2 gene to just produce more ( &

thus creating more SMN Protein & SMN Delta 7 protein).

I guess in answer to your question, if this was a test

and I had to drum up the best possible answer this

dumb guy's pin head can come up with is that SMN

protein production isn't the problem - its an issue

with the SMN complex as a whole - the protein

production ( & properly created) and the delivery

mechanism.

I'm sure there are far more elegant answers out there

- I'll scan through some things - I think I've heard

various doctors/researchers respond to this in the

past...

Mitch

--- <bristold@...> wrote:

> When I was going to school in Boston, I remember

> reading an article

> about a strange building under construction in the

> area that was

> nearing completion. People had been asking

> questions about it, and a

> reporter investigated. I forget the details, but

> the building was a

> new, multi-million dollar manufacturing plant for a

> biotech firm.

> The plant was going to manufacture a protein (I

> think) that was

> needed by a very small number of people in the

> world. I forget the

> disease, but the people affected were unable to

> produce this protein,

> and they would die without it. Tons of raw material

> went into one

> end of the plant, and milligrams of product would

> come out of the

> other end at an agonizingly slow rate. It was

> arguably the most

> valuable substance on earth, the reporter had said.

>

> The irony was - it was projected that the plant

> would be obsoleted

> shortly after it was started. Scientists were

> talking about

> genetically altering goats and having them produce

> milk that would

> contain the protein that was needed. The protein

> would almost become

> a commodity. The research was very promising.

>

> Of course, I drank an awful lot when I was in

> college in Boston, and

> my memory may not be that accurate.

>

> I did a quick Google search, and I found this:

> http://www.nexiabiotech.com/en/01_tech/05.php

>

> Has anyone else heard of this?

>

> Could this be a way for making SMN protein?

>

>

>

>

>

__________________________________________________

[Guest guest]

I've searched for info on artificially manufactured SMN protein

without much luck...

I understand that drugs that can force the SMN2 genes to work harder

may be the best bet, but from my limited knowledge of this disease,

it would seem that since those suffering from SMA are missing motor

neurons and the protein that protects them, and if it's not possible

(yet) to " repair " the faulty genes, then the true cure would be to

receive new motor neurons and daily doses of the protein that

protects them.

I've heard that researchers have already created motor neurons from

stem cells and have implanted them in mice with success, and that

human trials are scheduled in a couple of years. That stategy seems

like a good start, but it doesn't seem to make much sense if there is

not enough SMN protein to keep the neurons alive.

I e-mailed the company in that link, and I recently received a very

detailed reply from a consultant that used to work there. He is not

familiar with SMA or the SMN protein, but he said that just about any

protein can be created with this method - the only real problem

(depending on the type of protein) is the delivery method to get the

protein into the patient. He is going to look into it and get back

to me. But hey, what's a few shots? I had to get four a week for

allergies when I was young. If a parent can give their child a shot

every day to keep them completely symptom free, I think that's a

pretty good trade-off.

Yes, I'm a novice to all of this - but I am certainly going to do

everything that I can to make sure that every angle gets looked at.

> Jonathon:

>

> From this dumb guy's reading and thus far limited

> understanding of SMA, the problem isn't necessarilly

> just with the synthesis of SMN Protein. The problem

> is associated with the lack of SMN Protein in an

> area(s) where distributing the protein from an outside

> source would be very difficult if not impossible. The

> SMN Complex is a continual bodilly function whereby

> SMN Protein is created and delivered throughout the

> body - but only specifically dependent apparently in

> Motor Neurons - in the Anterior Horn Cells.

>

> Proteins of any sort can be created by using the

> recipes per the DNA code - some combination of the 20

> amino acids. Aside from difficulties associated the

> potential size of the recipe, are additional issues of

> how the protein is " folded " together - and the

> resulting physical shape of the protein. However, I

> don't think it would be all that difficult for SMN

> protein to be produced externally - I woulndn't doubt

> it if it has been done already.

>

> SMN Delta 7 protein (that which is predominantly

> produced by the SMN2 gene) - skips only a small

> section of the normal SMN protein (as coded from exon

> 7 which has been excluded to due 1 single coding

> mutation). Some researchers have been testing various

> small molecules that attach to SMN Delta 7 and cause

> it to appear more like regular SMN protein with some

> initial in vitro success. In vitro, by the way,

> simply refers to analysis in a lab dish or " in glass "

> (had to look that up a ways back) - versus In Vivo

> being in the body. But, aside from that, the SMN2

> gene sometimes still does produce the proper protein -

> about 10% of the time in just reads over the mutated

> neucleotide and exon 7 is not excluded. Thus - the

> current drug trials - to simply cause the SMN2 gene to

> do this more often - that is, be more efficient in

> producing SMN protein (vs SMN Delta 7 protein) by

> causing it to exclude exon 7 less often, or by sheer

> volume of cause the SMN2 gene to just produce more ( &

> thus creating more SMN Protein & SMN Delta 7 protein).

>

> I guess in answer to your question, if this was a test

> and I had to drum up the best possible answer this

> dumb guy's pin head can come up with is that SMN

> protein production isn't the problem - its an issue

> with the SMN complex as a whole - the protein

> production ( & properly created) and the delivery

> mechanism.

>

> I'm sure there are far more elegant answers out there

> - I'll scan through some things - I think I've heard

> various doctors/researchers respond to this in the

> past...

>

> Mitch

[Guest guest]

Jonathon:

You da man! Dig out as much info as you can on this!

Work over the consultant for as much info as you can

get & please pass it along!

Regarding the replacement of motor neurons, that's

still somewhat debatable as to whether the motor

neurons have actually died or are sick and

non-functioning ( & thus able to be recusitated back to

health). Also, it is quite possible that existing &

functioning motor neurons could, given additional SMN

protein, be made 'healthier' causing them to node of

additional connections with muscle tissue. The

doctors/researchers are not sure at what rate or the

overall rate of apoptisis (cellular suicide) is

associated with varying insufficient levels of SMN

protein - something that's being investigated.

I am more optimistic that 1) existing MN's will be

made more functional, 2) ill-nourished MN's will be

rescued, and 3) further MN loss will be halted, as a

result of the current drug trials. From the various

folks I've received responses back from, SC Research

and human trials for MN replacement or repair(at least

in the US) are at least a decade away for safety

reasons. I hope too, that this avenue of therapy

happens as it will ultimately bring more

physical/functional reversal possiblities for those

now with SMA. Who knows, with the pace of

advancements over the past 10 years, maybe that 10+

prediction of some turns out to be 4 or 5 in reality?

Who really knows...

Keep fightin the fight! Mitch

--- <bristold@...> wrote:

> I've searched for info on artificially manufactured

> SMN protein

> without much luck...

>

> I understand that drugs that can force the SMN2

> genes to work harder

> may be the best bet, but from my limited knowledge

> of this disease,

> it would seem that since those suffering from SMA

> are missing motor

> neurons and the protein that protects them, and if

> it's not possible

> (yet) to " repair " the faulty genes, then the true

> cure would be to

> receive new motor neurons and daily doses of the

> protein that

> protects them.

>

> I've heard that researchers have already created

> motor neurons from

> stem cells and have implanted them in mice with

> success, and that

> human trials are scheduled in a couple of years.

> That stategy seems

> like a good start, but it doesn't seem to make much

> sense if there is

> not enough SMN protein to keep the neurons alive.

>

> I e-mailed the company in that link, and I recently

> received a very

> detailed reply from a consultant that used to work

> there. He is not

> familiar with SMA or the SMN protein, but he said

> that just about any

> protein can be created with this method - the only

> real problem

> (depending on the type of protein) is the delivery

> method to get the

> protein into the patient. He is going to look into

> it and get back

> to me. But hey, what's a few shots? I had to get

> four a week for

> allergies when I was young. If a parent can give

> their child a shot

> every day to keep them completely symptom free, I

> think that's a

> pretty good trade-off.

>

> Yes, I'm a novice to all of this - but I am

> certainly going to do

> everything that I can to make sure that every angle

> gets looked at.

>

>

>

>

>

>

> > Jonathon:

> >

> > From this dumb guy's reading and thus far limited

> > understanding of SMA, the problem isn't

> necessarilly

> > just with the synthesis of SMN Protein. The

> problem

> > is associated with the lack of SMN Protein in an

> > area(s) where distributing the protein from an

> outside

> > source would be very difficult if not impossible.

> The

> > SMN Complex is a continual bodilly function

> whereby

> > SMN Protein is created and delivered throughout

> the

> > body - but only specifically dependent apparently

> in

> > Motor Neurons - in the Anterior Horn Cells.

> >

> > Proteins of any sort can be created by using the

> > recipes per the DNA code - some combination of the

> 20

> > amino acids. Aside from difficulties associated

> the

> > potential size of the recipe, are additional

> issues of

> > how the protein is " folded " together - and the

> > resulting physical shape of the protein. However,

> I

> > don't think it would be all that difficult for SMN

> > protein to be produced externally - I woulndn't

> doubt

> > it if it has been done already.

> >

> > SMN Delta 7 protein (that which is predominantly

> > produced by the SMN2 gene) - skips only a small

> > section of the normal SMN protein (as coded from

> exon

> > 7 which has been excluded to due 1 single coding

> > mutation). Some researchers have been testing

> various

> > small molecules that attach to SMN Delta 7 and

> cause

> > it to appear more like regular SMN protein with

> some

> > initial in vitro success. In vitro, by the way,

> > simply refers to analysis in a lab dish or " in

> glass "

> > (had to look that up a ways back) - versus In Vivo

> > being in the body. But, aside from that, the SMN2

> > gene sometimes still does produce the proper

> protein -

> > about 10% of the time in just reads over the

> mutated

> > neucleotide and exon 7 is not excluded. Thus -

> the

> > current drug trials - to simply cause the SMN2

> gene to

> > do this more often - that is, be more efficient in

> > producing SMN protein (vs SMN Delta 7 protein) by

> > causing it to exclude exon 7 less often, or by

> sheer

> > volume of cause the SMN2 gene to just produce more

> ( &

> > thus creating more SMN Protein & SMN Delta 7

> protein).

> >

> > I guess in answer to your question, if this was a

> test

> > and I had to drum up the best possible answer this

> > dumb guy's pin head can come up with is that SMN

> > protein production isn't the problem - its an

> issue

> > with the SMN complex as a whole - the protein

> > production ( & properly created) and the delivery

> > mechanism.

> >

> > I'm sure there are far more elegant answers out

> there

> > - I'll scan through some things - I think I've

> heard

> > various doctors/researchers respond to this in the

> > past...

> >

> > Mitch

>

>

>

__________________________________________________

[Guest guest]

I know I would love to have something that would resusitate my MN's or boost

the ones I have left. All I know is that the " plain jane aging process " is

what's chinking my MN's armour. So unless someone can stop humans from aging

aka " killing themselves off " then we're all SOL.

Angie

On 2005.09.06 12:27, wrote:

> Jonathon:

>

> You da man! Dig out as much info as you can on this!

> Work over the consultant for as much info as you can

> get & please pass it along!

>

> Regarding the replacement of motor neurons, that's

> still somewhat debatable as to whether the motor

> neurons have actually died or are sick and

> non-functioning ( & thus able to be recusitated back to

> health). Also, it is quite possible that existing &

> functioning motor neurons could, given additional SMN

> protein, be made 'healthier' causing them to node of

> additional connections with muscle tissue. The

> doctors/researchers are not sure at what rate or the

> overall rate of apoptisis (cellular suicide) is

> associated with varying insufficient levels of SMN

> protein - something that's being investigated.

>

> I am more optimistic that 1) existing MN's will be

> made more functional, 2) ill-nourished MN's will be

> rescued, and 3) further MN loss will be halted, as a

> result of the current drug trials. From the various

> folks I've received responses back from, SC Research

> and human trials for MN replacement or repair(at least

> in the US) are at least a decade away for safety

> reasons. I hope too, that this avenue of therapy

> happens as it will ultimately bring more

> physical/functional reversal possiblities for those

> now with SMA. Who knows, with the pace of

> advancements over the past 10 years, maybe that 10+

> prediction of some turns out to be 4 or 5 in reality?

> Who really knows...

>

> Keep fightin the fight! Mitch

>

> --- <bristold@...> wrote:

> > I've searched for info on artificially manufactured

> > SMN protein

> > without much luck...

> >

> > I understand that drugs that can force the SMN2

> > genes to work harder

> > may be the best bet, but from my limited knowledge

> > of this disease,

> > it would seem that since those suffering from SMA

> > are missing motor

> > neurons and the protein that protects them, and if

> > it's not possible

> > (yet) to " repair " the faulty genes, then the true

> > cure would be to

> > receive new motor neurons and daily doses of the

> > protein that

> > protects them.

> >

> > I've heard that researchers have already created

> > motor neurons from

> > stem cells and have implanted them in mice with

> > success, and that

> > human trials are scheduled in a couple of years.

> > That stategy seems

> > like a good start, but it doesn't seem to make much

> > sense if there is

> > not enough SMN protein to keep the neurons alive.

> >

> > I e-mailed the company in that link, and I recently

> > received a very

> > detailed reply from a consultant that used to work

> > there. He is not

> > familiar with SMA or the SMN protein, but he said

> > that just about any

> > protein can be created with this method - the only

> > real problem

> > (depending on the type of protein) is the delivery

> > method to get the

> > protein into the patient. He is going to look into

> > it and get back

> > to me. But hey, what's a few shots? I had to get

> > four a week for

> > allergies when I was young. If a parent can give

> > their child a shot

> > every day to keep them completely symptom free, I

> > think that's a

> > pretty good trade-off.

> >

> > Yes, I'm a novice to all of this - but I am

> > certainly going to do

> > everything that I can to make sure that every angle

> > gets looked at.

> >

> >

> >

> >

> >

> >

> > > Jonathon:

> > >

> > > From this dumb guy's reading and thus far limited

> > > understanding of SMA, the problem isn't

> >

> > necessarilly

> >

> > > just with the synthesis of SMN Protein. The

> >

> > problem

> >

> > > is associated with the lack of SMN Protein in an

> > > area(s) where distributing the protein from an

> >

> > outside

> >

> > > source would be very difficult if not impossible.

> >

> > The

> >

> > > SMN Complex is a continual bodilly function

> >

> > whereby

> >

> > > SMN Protein is created and delivered throughout

> >

> > the

> >

> > > body - but only specifically dependent apparently

> >

> > in

> >

> > > Motor Neurons - in the Anterior Horn Cells.

> > >

> > > Proteins of any sort can be created by using the

> > > recipes per the DNA code - some combination of the

> >

> > 20

> >

> > > amino acids. Aside from difficulties associated

> >

> > the

> >

> > > potential size of the recipe, are additional

> >

> > issues of

> >

> > > how the protein is " folded " together - and the

> > > resulting physical shape of the protein. However,

> >

> > I

> >

> > > don't think it would be all that difficult for SMN

> > > protein to be produced externally - I woulndn't

> >

> > doubt

> >

> > > it if it has been done already.

> > >

> > > SMN Delta 7 protein (that which is predominantly

> > > produced by the SMN2 gene) - skips only a small

> > > section of the normal SMN protein (as coded from

> >

> > exon

> >

> > > 7 which has been excluded to due 1 single coding

> > > mutation). Some researchers have been testing

> >

> > various

> >

> > > small molecules that attach to SMN Delta 7 and

> >

> > cause

> >

> > > it to appear more like regular SMN protein with

> >

> > some

> >

> > > initial in vitro success. In vitro, by the way,

> > > simply refers to analysis in a lab dish or " in

> >

> > glass "

> >

> > > (had to look that up a ways back) - versus In Vivo

> > > being in the body. But, aside from that, the SMN2

> > > gene sometimes still does produce the proper

> >

> > protein -

> >

> > > about 10% of the time in just reads over the

> >

> > mutated

> >

> > > neucleotide and exon 7 is not excluded. Thus -

> >

> > the

> >

> > > current drug trials - to simply cause the SMN2

> >

> > gene to

> >

> > > do this more often - that is, be more efficient in

> > > producing SMN protein (vs SMN Delta 7 protein) by

> > > causing it to exclude exon 7 less often, or by

> >

> > sheer

> >

> > > volume of cause the SMN2 gene to just produce more

> >

> > ( &

> >

> > > thus creating more SMN Protein & SMN Delta 7

> >

> > protein).

> >

> > > I guess in answer to your question, if this was a

> >

> > test

> >

> > > and I had to drum up the best possible answer this

> > > dumb guy's pin head can come up with is that SMN

> > > protein production isn't the problem - its an

> >

> > issue

> >

> > > with the SMN complex as a whole - the protein

> > > production ( & properly created) and the delivery

> > > mechanism.

> > >

> > > I'm sure there are far more elegant answers out

> >

> > there

> >

> > > - I'll scan through some things - I think I've

> >

> > heard

> >

> > > various doctors/researchers respond to this in the

> > > past...

> > >

> > > Mitch

>

> __________________________________________________

>

[Guest guest]

I don't know - this isn't sounding promising...

This is from the FSMA website:

Ernest Terwilliger - Beth Israel Hospital

W. Francis, PhD - Massachusetts General Hospital

" Targeted Restoration of SMN Gene Function to Spinal Cord Motor

Neurons "

The cause of SMA is a genetic defect which results in the loss of

one particular protein crucial for the survival of motor neurons.

Accumulating evidence suggests that if this protein could be

restored, it would be sufficient to cure the condition. This protein

acts within the neurons, and cannot simply be provided from the

outside. However, if new genes carrying the instructions for this

protein could be introduced into the neurons, this should restore the

cells to normal health. In this project we will show how novel viral

vectors can be used to deliver the gene for SMN protein into spinal

cord neurons.

They make it sound like just giving someone the SMN protein won't do

any good. The protein must be created within the neuron cell.

Of course, scrolling down shows a blurb from another researcher:

A. Kerr MD, PhD - s Hopkins University

" Investigation of a Role for Neural Stem Cells in Spinal Muscular

Atrophy "

In this proposal, we plan to examine the role for neural stem cells

in treatment of spinal muscular atrophy. Neural stem cells represent

a therapeutic intervention which, instead of combating the underlying

problem that gives rise to disease, serves to replace damaged and

dying cells and therefore, to improve function. We will utilize a

series of neural stem cells since at this time we do not know the

characteristics of a particular line that will result in functional

improvement. We will also examine an alternative strategy: that

neural stem cells may, rather than replacing dead motor neurons, may

serve to support and increase the function of those that are at risk

of dying. Finally, we will examine the possibility that SMN can be

delivered to at risk neurons from neural stem cells acting as a

continuous reservoir of secreted SMN.

This guy seems to think that SMN protein secreted by other cells will

help.

Do any of the researchers themselves come on this forum?

[Guest guest]

:

I believe the first article is more or less describing

the SMN Complex - which requires the SMN protein to be

derived internally. Which is the thought with simply

causing the SMN2 gene to produce more - one way, or

another.

The second article regarding gene therapy (versus drug

or small molecule therapy, or stem cell therapy) is

yet another avenue being investigated - for SMA, and

for a variety of neurological diseases. Researchers

are much more cautious with gene therapy at this

point, due to a child with DMD dying from various

complications during human trials of gene therapy for

DMD several years back. Gene therapy is happening -

successfully and in trials for a several diseases

right now, and based on articles like the one below,

should be a reality for SMA sometime in the near

future, I'd think.

Some of the researchers/doctors I know of will nose

around a bit hear and there. But I say screw it - if

you've got questions - go directly to the sources.

I've emailed at least 6 or 7 neurologists and 4 or 5

research/scientists with pretty direct questions.

With few exceptions, they have all replied to my

emails and to my questions. I have found the

doctors/researchers involved with SMA to be pretty

smart folks, pretty sensitive and compassionate to

requests from those affected by SMA, and pretty

responsive time-wise to any such requests. You can

find out most of these people's email addresses pretty

easily by a few clicks of the mouse...

Mitch

--- <bristold@...> wrote:

> I don't know - this isn't sounding promising...

>

> This is from the FSMA website:

>

> Ernest Terwilliger - Beth Israel Hospital

> W. Francis, PhD - Massachusetts General

> Hospital

>

> " Targeted Restoration of SMN Gene Function to

> Spinal Cord Motor

> Neurons "

> The cause of SMA is a genetic defect which results

> in the loss of

> one particular protein crucial for the survival of

> motor neurons.

> Accumulating evidence suggests that if this protein

> could be

> restored, it would be sufficient to cure the

> condition. This protein

> acts within the neurons, and cannot simply be

> provided from the

> outside. However, if new genes carrying the

> instructions for this

> protein could be introduced into the neurons, this

> should restore the

> cells to normal health. In this project we will show

> how novel viral

> vectors can be used to deliver the gene for SMN

> protein into spinal

> cord neurons.

>

>

>

> They make it sound like just giving someone the SMN

> protein won't do

> any good. The protein must be created within the

> neuron cell.

>

>

>

> Of course, scrolling down shows a blurb from another

> researcher:

>

> A. Kerr MD, PhD - s Hopkins University

> " Investigation of a Role for Neural Stem Cells in

> Spinal Muscular

> Atrophy "

> In this proposal, we plan to examine the role for

> neural stem cells

> in treatment of spinal muscular atrophy. Neural stem

> cells represent

> a therapeutic intervention which, instead of

> combating the underlying

> problem that gives rise to disease, serves to

> replace damaged and

> dying cells and therefore, to improve function. We

> will utilize a

> series of neural stem cells since at this time we do

> not know the

> characteristics of a particular line that will

> result in functional

> improvement. We will also examine an alternative

> strategy: that

> neural stem cells may, rather than replacing dead

> motor neurons, may

> serve to support and increase the function of those

> that are at risk

> of dying. Finally, we will examine the possibility

> that SMN can be

> delivered to at risk neurons from neural stem cells

> acting as a

> continuous reservoir of secreted SMN.

>

>

>

> This guy seems to think that SMN protein secreted by

> other cells will

> help.

>

>

>

> Do any of the researchers themselves come on this

> forum?

>

>

>

>

>

>

>

______________________________________________________

Click here to donate to the Hurricane Katrina relief effort.

http://store./redcross-donate3/

[Guest guest]

O.K. I made some nice progress with this, and at least I got some

people interested and talking.

Here is the first reply I got:

-------------

Hello ,

My name is and your recent technical question about

SMN protein was forward to me as the technical founder of Nexia

Biotech. I'm not with Nexia any more, but am still working in the

field of transgenic dairy animals to make novel protein drugs as a

consultant.

Your questions are very interesting and I would like to learn more as

I am not specifically familiar with this disease. Transgenic

production of authentic, recombinant versions of human proteins is a

reality today. The human protein of interest is manufactured in the

milk of goats [that way the protein can simply be collected in the

milk as opposed to having to kill the animal as is the case for pig

insulin production] and then purify it away from all the milk

components to from a drug which is injected into the patient. Such a

drug is currently nearing completion and clinical approval is Atyrn

® used to treat ATIII inherited deficiency.

Transgenic dairy goats have the biochemical production machinery to

produce virtually any human protein, and many others as well, our

recombinant spider silk for example. Do you have any technical

references or names of people researching this disease so that I

could learn more about the SMN protein? A second issue is how to

administer the recombinant SMN to patients. If the SMN can be

injected and still function, them your fine, however, if the SMN

protein must enter the neurons to function properly, then we have a

major problem because these big proteins can't cross the membranes

that surrounds the neuron.

I must caution you that to produce a transgenic dairy goat that has

the potential to make recombinant SMN protein is about a 12 month

project costing approximately $1 million. So its not done overnight

and its not cheap. The protein would be subject to US FDA or Health

Canada regulations to ensure that the drugs are safe and efficacious.

I hope that I have provide you with some answers to your questions.

My prayers go out to your daughter and your family. Unfortunately,

biology is sometimes very cruel.

With Kind Regards,

-----------------

I also sent an e-mail to Dr. Francis at MGH, because I thought that

he might be interested in it. He replied with this:

-----------------

Dear Mr. and Mrs. Goldsberry,

Your email was forwarded to me by a coworker here at MGH. You have

raised some interesting questions concerning the production of

recombinant SMN protein and its potential use as a therapeutic agent

in SMA. In theory, the recombinant SMN protein could be generated by

the means you have proposed (goats milk). I have done a fair amount

of work trying to target the delivery of recombinant SMN protein to

motor neurons, although the results of my studies were less than

encouraging. These results may, in part, have been attributable to

the fact that I was using recombinant protein obtained from bacteria.

I don't know whether generating the recombinant SMN in a different

expression host (goat) would ultimately result in better delivery to

motor neurons.

Sincerely,

W. Francis, Ph.D.

Assistant Professor of Neurology

----------------

A few more e-mails were exchanged, and I hooked Dr. Francis up with

Dr. . I got this response from Dr. :

----------------

Good Afternoon ,

I wanted to update you with regard to recombinant SMN protein drug

development and delivery systems.

I just got off the telephone with Dr. Francis, Department of

Neurology, Mass. General Hospital (MGH). He has some experience in

researching targeted delivery of protein drugs to motor neurons. You

will recall that delivering the drug to the " inside " or intracellular

part of the cell is a critical step. He told me that in his

experience, the SMN protein produced in bacterial systems is

insoluble and thus difficult to work with or deliver to neurons

because the SMN proteins aggregate together on the surface of the

neuron. A more soluble form of recombinant SMN (transgenic systems

make soluble proteins) may respond differently. Dr. Francis is open

to collaboration and has very useful assay systems to test

recombinant SMN for its function in mice and in cell culture. He

works in conjunction with Dr. Brown who is the Director of a

center at MGH studying motor neuron disorders. I have included him

on a cc so that we are all very transparent in these discussions, in

short a " teams win " approach.

Dr. Francis and I spoke about producing his big 3 part recombinant

protein (targeting + transmembrane + SMN) using our transgenic goat

approach. We think that it has some merit and are investigating the

ways and means of exploring it further in terms of technical

feasibility and financing. I'm planning on speaking with FSMA, but

must manage my expectations regarding the size of their research

grants.

So, as you can see, we're working away on various aspects of the

problem.

Regards,

--------------------

I must admit, this is really fun. I am so pleased that these

researchers are so open and willing to answer questions. I also got

a couple of very informative responses about how the proteins work

and what research is being done from Dr. Elliot Androphy at UMass.

[Guest guest]

Jonathon! Great recon, man! Keep it going! What

were the responses regarding how the proteins work?

Mitch

--- <bristold@...> wrote:

> O.K. I made some nice progress with this, and at

> least I got some

> people interested and talking.

>

> Here is the first reply I got:

> -------------

> Hello ,

>

> My name is and your recent technical

> question about

> SMN protein was forward to me as the technical

> founder of Nexia

> Biotech. I'm not with Nexia any more, but am still

> working in the

> field of transgenic dairy animals to make novel

> protein drugs as a

> consultant.

>

> Your questions are very interesting and I would like

> to learn more as

> I am not specifically familiar with this disease.

> Transgenic

> production of authentic, recombinant versions of

> human proteins is a

> reality today. The human protein of interest is

> manufactured in the

> milk of goats [that way the protein can simply be

> collected in the

> milk as opposed to having to kill the animal as is

> the case for pig

> insulin production] and then purify it away from all

> the milk

> components to from a drug which is injected into the

> patient. Such a

> drug is currently nearing completion and clinical

> approval is Atyrn

> ® used to treat ATIII inherited deficiency.

>

> Transgenic dairy goats have the biochemical

> production machinery to

> produce virtually any human protein, and many others

> as well, our

> recombinant spider silk for example. Do you have

> any technical

> references or names of people researching this

> disease so that I

> could learn more about the SMN protein? A second

> issue is how to

> administer the recombinant SMN to patients. If the

> SMN can be

> injected and still function, them your fine,

> however, if the SMN

> protein must enter the neurons to function properly,

> then we have a

> major problem because these big proteins can't cross

> the membranes

> that surrounds the neuron.

>

> I must caution you that to produce a transgenic

> dairy goat that has

> the potential to make recombinant SMN protein is

> about a 12 month

> project costing approximately $1 million. So its

> not done overnight

> and its not cheap. The protein would be subject to

> US FDA or Health

> Canada regulations to ensure that the drugs are safe

> and efficacious.

>

> I hope that I have provide you with some answers to

> your questions.

> My prayers go out to your daughter and your family.

> Unfortunately,

> biology is sometimes very cruel.

>

> With Kind Regards,

>

>

> -----------------

> I also sent an e-mail to Dr. Francis at MGH, because

> I thought that

> he might be interested in it. He replied with this:

> -----------------

> Dear Mr. and Mrs. Goldsberry,

>

> Your email was forwarded to me by a coworker here at

> MGH. You have

> raised some interesting questions concerning the

> production of

> recombinant SMN protein and its potential use as a

> therapeutic agent

> in SMA. In theory, the recombinant SMN protein

> could be generated by

> the means you have proposed (goats milk). I have

> done a fair amount

> of work trying to target the delivery of recombinant

> SMN protein to

> motor neurons, although the results of my studies

> were less than

> encouraging. These results may, in part, have been

> attributable to

> the fact that I was using recombinant protein

> obtained from bacteria.

> I don't know whether generating the recombinant SMN

> in a different

> expression host (goat) would ultimately result in

> better delivery to

> motor neurons.

>

>

> Sincerely,

>

> W. Francis, Ph.D.

> Assistant Professor of Neurology

> ----------------

> A few more e-mails were exchanged, and I hooked Dr.

> Francis up with

> Dr. . I got this response from Dr. :

> ----------------

> Good Afternoon ,

>

> I wanted to update you with regard to recombinant

> SMN protein drug

> development and delivery systems.

>

> I just got off the telephone with Dr.

> Francis, Department of

> Neurology, Mass. General Hospital (MGH). He has

> some experience in

> researching targeted delivery of protein drugs to

> motor neurons. You

> will recall that delivering the drug to the " inside "

> or intracellular

> part of the cell is a critical step. He told me

> that in his

> experience, the SMN protein produced in bacterial

> systems is

> insoluble and thus difficult to work with or deliver

> to neurons

> because the SMN proteins aggregate together on the

> surface of the

> neuron. A more soluble form of recombinant SMN

> (transgenic systems

> make soluble proteins) may respond differently. Dr.

> Francis is open

> to collaboration and has very useful assay systems

> to test

> recombinant SMN for its function in mice and in cell

> culture. He

> works in conjunction with Dr. Brown who is

> the Director of a

> center at MGH studying motor neuron disorders. I

> have included him

> on a cc so that we are all very transparent in these

> discussions, in

> short a " teams win " approach.

>

> Dr. Francis and I spoke about producing his big 3

> part recombinant

> protein (targeting + transmembrane + SMN) using our

> transgenic goat

> approach. We think that it has some merit and are

> investigating the

> ways and means of exploring it further in terms of

> technical

> feasibility and financing. I'm planning on speaking

> with FSMA, but

> must manage my expectations regarding the size of

> their research

> grants.

>

> So, as you can see, we're working away on various

> aspects of the

> problem.

>

> Regards,

> --------------------

>

> I must admit, this is really fun. I am so pleased

> that these

> researchers are so open and willing to answer

> questions. I also got

> a couple of very informative responses about how the

> proteins work

> and what research is being done from Dr. Elliot

> Androphy at UMass.

>

>

>

>

>

>

__________________________________________________