Disputed Secretin Study Makes Prestigious Journal - Commentary

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" Healing Autism: No Finer a Cause on the Planet "

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Disputed Secretin Study Makes Prestigious Journal - Commentary

Wednesday, December 08, 1999

[The following information and commentary is provided by

LeGendre, Ph.D. (NLeGendre@...), mother of two autistic spectrum

daughters.]

By the end of this day, I expect that each of you will have heard some

mention of autism on the news wires. Be listening to NPR, USA Today, New

England Cable News, the CNN website, ABC in Boston, and the WSJ for

starters.

While this kind of coverage is often reason to celebrate in our

community, that will not be the case today. Today's story is precipitated

by the publication of the results of the Asheville, No. Carolina clinical

trial on secretin in the New England Journal of Medicine (NEJM). Sandler et

al find " no effect over placebo " for secretin in a single dose, double blind

trial on 28 autistic and PDD children. The reporting of this study is not

new to most folks on these lists as the Sandler abstract was previously

posted on the [autism related] lists, including in the FEAT newsletter [ " One

of Many Secretin Studies Start Rolling In, " June 19, 1999 and " Physician

Responds to Secretin Study Report, " June 22, 1999; reprinted below.] What

is new is that the study has been given new validity by virtue of

publication in the prestigious NEJM. It is also accompanied by an editorial

written by Fred Volkmar, M.D. of Yale entitled, " Lessons of Secretin. "

Specifically because of this reporting, Repligen lost on the order of

$35 million in stock value. To date, Repligen has raised $9 million in

capital to be directed towards research and development in autism. A

significant loss in stock value makes it difficult for Repligen to return to

Wall Street for additional capital investment.

Aside from the financial blow, there is more going on here... far

more. Those of us who have previously reviewed the original Pediatric News

abstract of the Sandler study readily pointed out the many faults of that

study. Outstanding amongst those faults are

1. very poor statistics,

2. a single dose is inadequate to assess the efficacy of any biologic, and

3. there were NO clear selection criteria for the 28 autistic study

participants. For example, secretin is a gastrointestinal hormone, and

there was no attempt to select on the basis of gastrointestinal issues. The

children were also older than the originally reported responders (Horvath et

al) and relatively verbal and high-functioning. It is hard to comprehend

that a meager study led by psychologists might effectively condemn the

development of secretin as a biological treatment in autism.

Volkmar, in his editorial, challenges the media to cover the negative

trial results with as much fervor as they covered the initial, parentally

based reports of success. He admonishes parents to take notice; these

results confirm that we need to wait for scientists to confirm efficacy

before trying potential medical therapies on our children. In other words,

a single poorly designed clinical trial on 28 participants (only 18

diagnosed with autism; the remainder were PDD), in his mind, outweighs the

hundreds (and perhaps 1000's) of optimistic outcomes reported by parents and

their clinicians. What Volkmar doesn't tell us, is how long we will be

waiting for new therapies in autism.

What else is happening here? I will let you be the judge but will

provide a few facts. Marie Bristol-Powers, Duane and the National

Institute of Child Health and Human Development (NICHD) issued a press

release in response to the NEJM report. In addition to reiterating the

findings in the Sandler study, the NICHD statement implies that desperate

parents are spending their last dollar to obtain secretin. The NICHD goes

on record decrying safety concerns: " Secretin may be promising, but it may

also be hazardous, " Dr. Bristol Power said. " Its use at this time is

probably best supervised in a carefully controlled clinical trial. "

In fact, in an overt attempt to scare parents away from the off label

use of secretin, Bristol Powers and colleagues initially wrote that the

amino acid, cysteine, present in some preparations of secretin, is a

neurotoxin, " capable of destroying nerve and brain cells. " Why then is

cysteine a common stabilizer found in many FDA approved formulations? Why

did the NICHD, in fact, fund clinical trials of secretin in autism knowing

that the formulation contains a neurotoxin? Realizing their error, these

statements have been removed from a second NICHD press release referring to

these initial secretin trial results.

Ironically, much of the negativism re. secretin and the pursuit of

biological treatment options in autism has come from the psychology/

behavioral community that has served this population of children for

decades. One must question their motive for dismissing secretin even as

they routinely prescribe SSRI's (Prozac, Zoloft, etc.) and neuroleptics for

off label use in our children. These drugs are wholly untested for efficacy

and safety in autistic children. Is there a double standard here?

And, still, I have not entirely given up hope re: pursuing biomedical

treatment directions for autism. I look forward to participating in the

April 8, 2000 autism awareness march on Washington. I invite each of you to

contribute squares to the quilt I am preparing to display in Washington as a

visual reminder of our childrens' plight. Even more importantly,

congressional hearings on autism are planned to coincide with the April

march. This is, indeed, a call to immediate action. [Autism Rally

information provided below.]

Your voice, too, is needed.

LeGendre, Ph.D (NLeGendre@...)

mother of two autistic spectrum daughters

* * *

Physician Responds to Secretin Study Report

Reprinted from the June 22, 1999 FEAT Newsletter

[Last Saturday, June 19, we ran a report on the findings of the first

ofmany secretin studies to come to our attention. The study, " A

DOUBLE-BLIND,PLACEBO-CONTROLLED STUDY OF SYNTHETIC HUMAN SECRETIN IN THE

TREATMENT OFAUTISM AND PERVASIVE DEVELOPMENTAL DISORDER (PDD). " by A.D.

Sandler, etal., concluded that secretin performed no better than placebo

inameliorating the symptoms of autism.]

From E. Layton, M.D.:mailto:layton@...

I am a physician who has treated over 125 children with IV Secretin.

After reading the information about the lack of response to the

infusion of human Secretin to 60 children with Autism, I have the following

comments:

1. I am delighted to see that double-blind placebo-controlled studies

have started. Hopefully, we will be seeing more of the same.

2. I am concerned that this study does not reflect the positive

results I have been seeing with my patients. The fact that human Secretin

was used in a dosage of .4 micrograms per kilogram may have influenced the

lack of positive results from this particular study. I personally have used

Ferring Secretin and recently Gaspretin (also a pork source) Secretin. The

dosage I am using is 2 units per kilogram contrasted to the this study's .4

micrograms per kilogram with human Secretin. I would like feedback on the

comparison of these two forms of Secretin--human vs. pork source and 2

clinical units per kilogram of Ferring--Gaspretin versus .4 micrograms per

kilogram of Synthetic human Secretin.

Finally, it has been my experience that a number of children do not

respond until the second or third infusion. Clinically, IV Secretin has been

the most effective treatment for at least 60% of the children I have

evaluated with a diagnosis of Autism Spectrum Disorder.

Sincerely,

E. Layton, M.D. mailto:layton@...

* * *

Rally for National Autism Awareness - April 8 Washington DC

Reprinted from Monday, October 25, 1999

[From " Open Your Eyes to Autism " and Hear~Their~Silence]

Autism groups and parents are urged to unite April 8, 2000 for a Rally

for National Autism Awareness!

The Goal:

The Autism Resource Konnection in its grass roots effort to assist

individuals, parents, and families that face the challenges Autism brings,

along with Unlocking Autism with their " Open Your Eyes to Autism " picture

collection project, embraced the need for National public Awareness by

promoting the first ever Rally for National Autism Awareness. Largely as

the result of the truly inspiring speech from Beck, and her

picture slide show of Autistic children set to the lyrics of " Stand Up!

Speak Out! Let Your Voice be Heard - It's going to take each one of us to

change our children's world.. " . The Autism Resource Konnection is committed

more than ever to unite the Autism community together to do just that.

The Issues Behind Autism: We need to change how Autism is depicted.

The medical protocol Pediatrician's use to treat or fail to treat Autism,

how insurance treats Autism, how schools educate our children with Autism,

the legislation pertaining to Autism, and other issues needing to be brought

to the forefront.

Autism is rising and rising, and we still do not have adequate funding

to find out why. We need to urge the government to start an Autism Task

Force to investigate the issues surrounding: how can be better the early

intervention services; once in the schools how do we make the educational

setting more appropriate for an Autistic child - making ABA type styles a

choice along with inclusion - instead of the standard " catch all " style

currently in place; and lastly, what are we going to do with this generation

of Autistic children when the reach 21?? The government has not been made

to see these issues on a large scale with the sheer numbers of children

involved. Not to mention all the medical and nutritional research being

done and largely ignored.

The government needs to see the urgency of increased funding and

research, and the necessity of clinical trials for possible treatments for

our children now, not 5 years from now. If it is vaccine related in some

way, we have to investigate that now, to prevent another Autistic

generation. Research the possible genetic, environmental, or toxin causes.

Fund a national database to see what all these children may have in common.

The Groups Who Have United Together: The Autism Resource Konnection's

(http://www.ark-inc.org) mission is to increase public Awareness of Autism

throughout the Nation, and assist individuals, parents, and families that

face the challenges this disability brings everyday.

____________________________________________________________

editor: Lenny Schafer schafer@... | * Not FEAT

eastern editor: , PhD CIJOHN@...

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