Re: CSF study

[Guest guest]

Hi :

Am I right in assuming you would need a spinal tap done along with the

blood work? Would the samples be shipped something like they would for

Dr.

Siddique's study and would Canada be included in the testing?

Jo.

CSF study

If anyone is intereste in taking part in this study, please email

me, Thomson

jthomson@...

I'm collecting names for now. Once I have enough participants I

will forward the info to Dr. Bowser. We need all the participants

we can get to get this rolling.

Diagnostic Biomarkers for PLS

The factors that initiate primary lateral sclerosis (PLS) and the

ways in which the disease progresses remain unknown. Novel insight

into these critical questions requires using new approaches. Dr.

Bowser and colleagues at the University of Pittsburgh School

of Medicine have recently used a new technology called proteomics to

identify a panel of protein biomarkers from the cerebrospinal fluid

(CSF) of ALS patients that can be used for diagnosis. The

identification of biomarkers permits a more rapid diagnosis of the

disease and may offer an improved means to evaluate drug

effectiveness in clinical trials, thus enhancing our ability to find

effective drug treatments. We propose that a similar panel of

biomarkers can be identified from the CSF of PLS patients, and

biomarker panels can be identified specifically from PLS patients

with a limb versus bulbar onset.

The overall project will be to obtain CSF by a lumbar puncture from

between 10 - 20 patients with limb onset PLS, 10 - 20 patients with

bulbar onset PLS, and 10 - 20 patients with slowly progressing ALS.

The CSF samples will be examined by mass spectrometry to

characterize all the proteins present in the CSF from each person.

Mass spectrometry is a technology that can rapidly separate and

identify all the individual proteins contained in a complex mixture

like CSF. These results will be compared to one another and to

another group of control subjects without any disease. From these

experiments we hope to identify a series of proteins that are

specifically found in PLS patients with limb onset, another set of

proteins specific to PLS patients with bulbar onset, and a final set

of proteins specific to patients with very slowly progressing ALS.

Each set of proteins is called a panel of biomarkers specific for

each disease variant. We will then determine the identification of

each protein biomarker. This knowledge will help us identify novel

targets for drug therapy. The biomarker panels will also enable a

rapid diagnosis for PLS and each subtype.

The amount of CSF required for the study is quite small, only about

1 teaspoon. However each patient must consent for a lumbar puncture

and for our use of the CSF in this research study. All CSF samples

must be carefully shipped to the University of Pittsburgh for

analysis. It is also important to obtain information regarding each

patient (name, age, gender, race, date of diagnosis, medical

diagnosis, site of disease onset, medications currently taking, and

medical or surgical history). This will greatly assist in our study.

Our proposed study will lead to reliable biomarkers for the

diagnosis of PLS and determine if the biomarkers are specific to the

site of disease onset. PLS specific biomarkers will be used to

identify potential novel therapeutic targets for future drug design,

thus greatly advancing and speeding our search for potential drug

treatments. This novel study can only be performed with the consent

and interest of patients in the PLS community.

Thomson, Solana Beach, CA

www.als-pls.org

[Guest guest]

Hi Jo,

The spinal tap is all that Dr. Bowser needs. Yes, it would be

shipped similar to the Northwestern study. Dr. Bowser would send

you all the info you need. I'm sure Canada is fine with him.

[Guest guest]

Hi :

Thank you for your reply.

I see my Internist Physician on Monday ( & he is the one who did my

previous spinal tap and did an excellent job). I don't see my Neurologist

until beginning of March so I will run it by my Internist on Monday and get

his comments.

Is there a deadline that this has to be done by??

Take care.

Jo!

Re: CSF study

> Hi Jo,

> The spinal tap is all that Dr. Bowser needs. Yes, it would be

> shipped similar to the Northwestern study. Dr. Bowser would send

> you all the info you need. I'm sure Canada is fine with him.

>

>

>

>

>

>

>

[Guest guest]

Hi Jo,

There is no rush right now, I'm trying to see if enough people will

volunteer. No sense in drawing the fluids if we don't have enough

to actually do anything with it.

So, anyone else want to volunteer?

I'm going to do it.

[Guest guest]

Heres an idea .if people have had Lumbar Punctures there would be

records of it on their med records this can be forwarded to whoever .Ive had one

and they dont want to tell me why my Protein count was double ,i beleive they

dont know. not to rain on your parade but this is why i dont beleive i would

partake in this Sorry GEO

Re: CSF study

Hi Jo,

There is no rush right now, I'm trying to see if enough people will

volunteer. No sense in drawing the fluids if we don't have enough

to actually do anything with it.

So, anyone else want to volunteer?

I'm going to do it.

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

[Guest guest]

, et. al.,

Wouldn't this be particularly helpful when new people are diagnosed? Seems

like many of us had to get spinal taps and at that time a tiny amount of that

fluid could have been sent to Dr. Bowser. We really need to somehow

educate the patients and doctors at the time of that first spinal tap.

(Did that make sense?) 'Course that's the ideal...but if you do it, I will

too.

Alone we can do so little. Together we can do so much.

Helen Keller (1880-1968)

[Guest guest]

Geo,

Dr. Bowser needs the actual spinal fluid to run through special

equipment that will analyze proteins. I doubt that the spinal fluid

you had drawn was preserved. And I'm sure they didn't run it

through the equipment that Dr. Bowser uses.

The researchers don't know what these proteins do yet, but they do

know that they are indicative of ALS.

Once a pattern of proteins is identified, work can start on

discovering what those proteins do. You have to start somewhere.

With PLS, we don't know what proteins might be present. Could be

the same ones as in ALS, could be different ones. Maybe some the

same and some different. We won't know unless we do the research.

If everyone had the attitude that they wouldn't participate in

research because the researchers don't have all the answers, then

we'd never find any answers. Again, you have to start somewhere.

Below is the original posing about Dr. Bowser's work. He is also

going to present at the PLS Symposium in June.

Protein biomarkers boost ALS research

24 November 2003 9:00 GMT

by Jo Whelan

Researchers investigating the fatal neurodegenerative

condition amyotrophic lateral sclerosis (ALS) have

pinpointed the first biomarkers for the disease. In

addition to their diagnostic potential, the markers

should shed light on the disease process itself, they

report.

Also known as motor neuron disease, ALS is a

progressive degeneration of the motor neurons in the

brain and spinal cord. These cells control the muscles

used for locomotion, speaking, swallowing and

breathing, and without them the muscles weaken and

waste. Life expectancy from diagnosis is 2-5 years.

Worldwide there are about 120,000 new cases diagnosed

a year. There is one licensed drug treatment,

riluzole, but it prolongs life only slightly, several

other drugs are in trials.

A total of 15 biomarkers for the disorder have been

discovered by a team at the University of Pittsburgh,

Pennsylvania, led by Bowser. The researchers

examined the cerebrospinal fluid (CSF) of 20 people

recently diagnosed with ALS, and 20 controls. CSF is

in close contact with motor neurons and brain cells

called glia, which are also affected by ALS.

The researchers analyzed the protein content of the

CSF samples using a new mass spectrometry technique

called SELDI-TOF (surface enhanced laser desorption

ionization - time of flight). Analysis of the data

revealed a panel of 15 proteins that predict ALS with

100% sensitivity, report Bowser's team. Specificity -

the degree to which false positive predictions are

eliminated - was around 85%, but this is expected to

improve as more samples are added to the dataset.

Work is now underway to sequence and identify the

proteins. " We don't know at the moment if they are

alterations or degradation products of existing

proteins, or changes of protein expression, or whether

these are novel proteins, " said Bowser. " If some turn

out to be well-known proteins, it could rapidly lead

to new insights into the pathogenesis of ALS. If they

are new proteins we would have to develop functional

assays for them, which could take another year. "

It is not known why the motor neurons of ALS patients

die, though researchers predict that programmed cell

death, apoptosis, is probably involved. " We have

various hints, " said Bowser, " but we really don't know

the key biochemical pathways to cell death. If some of

the biomarkers are linked to particular pathways, it

will point us towards those pathways as being

important. I think we will obtain some very important

information. "

Once characterized, the biomarkers will be used to

develop the first diagnostic test for ALS. Clinical

diagnosis is difficult, hampering both patient care

and research into new treatments. " In the lab we can

diagnose ALS from a CSF sample in about six hours, "

said Bowser.

A CSF-based test would enable doctors to assess the

effectiveness of potential drug treatments in reducing

protein abnormalities, though more research will be

needed to see whether any such reductions correlate

with clinical improvement. " We know that the pattern

of biomarkers changes during disease progression, and

we're currently trying to recruit more patients to

study the pattern of that change, " Bowser said. The

team plan to analyse another 100-200 CSF samples in

the next few months.

" Finding biomarkers is a top priority in ALS

research, " said Belinda Cupid, research coordinator

for the UK-based Motor Neurone Disease Association.

" This work is timely, and the techniques used are

novel and elegant. However, until the proteins are

identified they can't yet be confirmed as specific ALS

biomarkers. "

Bowser presented the work in Milan at the

International Symposium on ALS/MND in November

[Guest guest]

Yes, it would be helpful if we could just use some of what is drawn

when you are going through all the testing to get a diagnosis. The

only problem is that right now most of the neuros out there don't

know that this study is taking place for PLSers.

So if anyone on the list is scheduled for a spinal, then now is the

time to request that some of the fluid be sent to Dr. Bowser. Saves

an extra poke :-)

I'm definitely going to do it so I'm putting you on the list also!

> , et. al.,

>

> Wouldn't this be particularly helpful when new people are

diagnosed? Seems

> like many of us had to get spinal taps and at that time a tiny

amount of that

> fluid could have been sent to Dr. Bowser. We really need to

somehow

> educate the patients and doctors at the time of that first spinal

tap.

> (Did that make sense?) 'Course that's the ideal...but if you do

it, I will

> too.

>

>

>

> Alone we can do so little. Together we can do so much.

> Helen Keller (1880-1968)

>

>

>

[Guest guest]

Hi, everyone,

Last year I participated in a study being done by a researcher at

Wake Forest University School do Medicine. The purpose of the study

was to compare blood and spinal fluid of ALSers and a control group

to try to identify elements that might be different between the two

groups. I ws in the control group.

Blood was drawn as was spinal fluid via a lumbar puncture. The

paperwork that I was required to read and sign noted that a portion

of the items collect would be stored for future testing. I do not

think that the researcher has published and results, but the

information that I received indicated that differences were

identified.

Don

[Guest guest]

Hi ,

This is so interesting and my prayer will be more specific now. Thank you for

the information on the proteins. Take care.

God Bless

Yolanda

Re: CSF study

Geo,

Dr. Bowser needs the actual spinal fluid to run through special

equipment that will analyze proteins. I doubt that the spinal fluid

you had drawn was preserved. And I'm sure they didn't run it

through the equipment that Dr. Bowser uses.

The researchers don't know what these proteins do yet, but they do

know that they are indicative of ALS.

Once a pattern of proteins is identified, work can start on

discovering what those proteins do. You have to start somewhere.

With PLS, we don't know what proteins might be present. Could be

the same ones as in ALS, could be different ones. Maybe some the

same and some different. We won't know unless we do the research.

If everyone had the attitude that they wouldn't participate in

research because the researchers don't have all the answers, then

we'd never find any answers. Again, you have to start somewhere.

Below is the original posing about Dr. Bowser's work. He is also

going to present at the PLS Symposium in June.

Protein biomarkers boost ALS research

24 November 2003 9:00 GMT

by Jo Whelan

Researchers investigating the fatal neurodegenerative

condition amyotrophic lateral sclerosis (ALS) have

pinpointed the first biomarkers for the disease. In

addition to their diagnostic potential, the markers

should shed light on the disease process itself, they

report.

Also known as motor neuron disease, ALS is a

progressive degeneration of the motor neurons in the

brain and spinal cord. These cells control the muscles

used for locomotion, speaking, swallowing and

breathing, and without them the muscles weaken and

waste. Life expectancy from diagnosis is 2-5 years.

Worldwide there are about 120,000 new cases diagnosed

a year. There is one licensed drug treatment,

riluzole, but it prolongs life only slightly, several

other drugs are in trials.

A total of 15 biomarkers for the disorder have been

discovered by a team at the University of Pittsburgh,

Pennsylvania, led by Bowser. The researchers

examined the cerebrospinal fluid (CSF) of 20 people

recently diagnosed with ALS, and 20 controls. CSF is

in close contact with motor neurons and brain cells

called glia, which are also affected by ALS.

The researchers analyzed the protein content of the

CSF samples using a new mass spectrometry technique

called SELDI-TOF (surface enhanced laser desorption

ionization - time of flight). Analysis of the data

revealed a panel of 15 proteins that predict ALS with

100% sensitivity, report Bowser's team. Specificity -

the degree to which false positive predictions are

eliminated - was around 85%, but this is expected to

improve as more samples are added to the dataset.

Work is now underway to sequence and identify the

proteins. " We don't know at the moment if they are

alterations or degradation products of existing

proteins, or changes of protein expression, or whether

these are novel proteins, " said Bowser. " If some turn

out to be well-known proteins, it could rapidly lead

to new insights into the pathogenesis of ALS. If they

are new proteins we would have to develop functional

assays for them, which could take another year. "

It is not known why the motor neurons of ALS patients

die, though researchers predict that programmed cell

death, apoptosis, is probably involved. " We have

various hints, " said Bowser, " but we really don't know

the key biochemical pathways to cell death. If some of

the biomarkers are linked to particular pathways, it

will point us towards those pathways as being

important. I think we will obtain some very important

information. "

Once characterized, the biomarkers will be used to

develop the first diagnostic test for ALS. Clinical

diagnosis is difficult, hampering both patient care

and research into new treatments. " In the lab we can

diagnose ALS from a CSF sample in about six hours, "

said Bowser.

A CSF-based test would enable doctors to assess the

effectiveness of potential drug treatments in reducing

protein abnormalities, though more research will be

needed to see whether any such reductions correlate

with clinical improvement. " We know that the pattern

of biomarkers changes during disease progression, and

we're currently trying to recruit more patients to

study the pattern of that change, " Bowser said. The

team plan to analyse another 100-200 CSF samples in

the next few months.

" Finding biomarkers is a top priority in ALS

research, " said Belinda Cupid, research coordinator

for the UK-based Motor Neurone Disease Association.

" This work is timely, and the techniques used are

novel and elegant. However, until the proteins are

identified they can't yet be confirmed as specific ALS

biomarkers. "

Bowser presented the work in Milan at the

International Symposium on ALS/MND in November