The following correspondence is in response to the Pompe disease research article that was published in the March 2003 issue of “Quest” an MDA publication.  

From:                                                       

Marylyn House                                                          

AMDA

Acid Maltase Deficiency Association

March 12, 2003

TO:

MDA—“QUEST”

In the "early days" the MDA was not as supportive of Pompe research as was suggested in the "Quest" article (March 2003).  FolIowing is (past) correspondence between AMDA and MDA indicating that there was not a great deal of interest by the MDA in the promotion of Pompe endeavors….

……(an) area (of Pompe research) overlooked in the "Quest" article (was)…. the work done by the researchers in the Netherlands where the FIRST clinical trials originated  5-6 months prior to Duke's trials.........and they were very successful.  

Dr. Reuser and Dr. van der Ploeg (scientists in The Netherlands) were precursors of research in Pompe's disease, and their work should not have been overlooked by the MDA (or by Genzyme or Duke). All parties (Duke, Genzyme, MDA) were well aware of the research and the clinical trials that took place in the Netherlands (MDA contacted Dr. Reuser in regards to his Pompe research in 1998).

We were aware that Genzyme was arranging a "campaign" with the MDA to publicize their new clinical trial (for Pompe’s disease).  We requested that AMDA and the IPA (International Pompe Association) be included in the meeting because of our prior involvement and contributions to the Pompe “project”, but our request was denied…..

>>I was just wondering if you guys (AMDA) have read the article in this month’s Quest Magazine (MDA’s magazine) about Pompe disease yielding to modern medicine.  I was just wondering what information your organization has received on these trials, and if you know of any other information. The article was very positive.  Dr. Chen’s work at Duke University was highlighted, and so was one of the case studies.

IT IS VERY RARE THAT ACID MALTASE DISEASE IS DISCUSSED IN THIS MAGAZINE.

Please let us know what you have received on this data.  We are very interested in any information your have<<

Genzyme has been collaborating with MDA for months on developing a campaign for Pompe's disease.  MDA was not much interested in "us" (the Pompe patients) until Genzyme entered the picture.  I think we are going to see a lot more MDA involvement and "credit taken" in the future.  The MDA is one of the largest non-profit organizations in the world with "celebrity" recognition.  So..........Genzyme wanted their "name" in the game.

Best Regards,
Marylyn House
AMDA

LETTER FROM A MEMBER OF GSDNET FOLLOWS

>>I only know what I read from their (MDA’s Quest) publications (March-April 2003), but I thought they paid for a lot of the original research, and some of the more recent also.
M.<<

I'm not aware of them (MDA) paying one cent towards the original ERT research, which was carried out in Rotterdam. Nor did they make the running in taking that original research forward. For that, we have to thank - aside from the researchers themselves - the remarkable achievements of Randall and Marylyn House (AMDA). Make no mistake, they *made* things happen.

In fact, one of the interesting threads to the Pompe's story (in my view) is the combination of European ideas and US 'can-do' - another example being that other remarkable US couple, John and Eileen Crowley.

FROM MARYLYN HOUSE TO GSDNET

>>On the other hand if MDA gives money towards the project to build more bioreactors would that not improve the time problem towards ERT becoming available to all patients around the world<<


REPLY TO THE ABOVE LETTER FROM MARYLYN HOUSE

I do not think that MDA will fund bioreactors----this is the corporation's (Genzyme) role----they (MDA) are research oriented.  I do not have any objection to MDA's involvement--we (AMDA) requested their involvement early on, but we were rebuffed!

What I do resent is their claim that they took the lead and that MDA (and Duke University) are the keys to the development of the whole Pompe project….

No doubt that it will take an institution like the MDA to get the coverage necessary to educate and inform the medical community (and insurance carriers and the government!) about Pompe's disease.  This is good! 

BUT.........…………………………………..

It is, once again, an example of how things are slanted. With all of their financial resources and influence, the MDA should be a leader in research initiatives not a usurper of credit!!!! (and the same goes for other entities as well).

Marylyn House
AMDA

On January 24, 1996, the MDA was asked to support and attend the first AMDA Scientific Conference held in San Antonio, Texas in March 1996.

From:
Dr. Y. T. Chen

Duke University

To:
Norine Stirpe, Ph.D.
Director of Research Development
National Headquarters 3300 East Sunrise Drive
Tucson, AZ 85718-3208

Conference Objectives:
To gather the principal investigators worldwide to discuss and share information on Pompe disease and to plan a collaborative effort to find a cure for Pompe disease.

Dear Dr. Stirpe:
Enclosed you will find my official application requesting the funding for the Pompe Disease Meeting to be held in March (1996).  I am sending this per your advice and upon the request of Mr. Randall House who is the President of the Acid Maltase Deficiency Association.

I hope this is the information you will need but if there are any further questions or concerns please do not hesitate to contact me….  Thank you very much for your time and consideration.

Sincerely,

Y.T. Chen, M.D., Ph.D.
Professor of Pediatrics and Genetics,
Chief, Division of Medical Genetics
Duke University Medical Center

Dear Dr. Chen,
Thank you for your January 24 letter and the grant request it transmitted seeking support for the March symposium on acid maltase deficiency being held under the aegis of the Acid Maltase Deficiency Association.  Through its Special Grants Program, MDA does consider requests for supplemental support of meetings. However, as a result of current fiscal imperatives, our budget for support of such meetings is severely limited and all requests for supplemental meeting support must necessarily be closely evaluated.  For this reason we regret that we are not able to respond positively to the request for supplemental support the March Acid Maltase Deficiency Meeting.......

Ronald J. Schenkenberger
Director of Research & Patient Services Administration

cc: Karen Mashburn-Grants Coodinator

To:
Karen Mashburn
Grants Coordinator
Muscular Dystrophy Association
National Headquarters
Tucson, Arizona

Dear Ms. Mashburn,
I received your response of February 9,1996, responding to the request for funding for the conference of March 21-22, 1996, in San Antonio, Texas, sponsored by the Acid Maltase Deficiency Association, a non-profit organization.  This request was made on behalf of the Association by

Dr. Y. T. Chen at Duke University.  I am disappointed that the MDA will not be able to co-sponsor the meeting with the Association, but I would like to request that the MDA have a representative present at the meeting.

This is the first time that the key investigators, worldwide, will be gathered together to focus on this devastating disease.  We have received enthusiastic response form the investigators in this field and representation by the MDA would certainly be in order since this falls under your genetic disease program.

Following is a list of the investigators that will be attending and making presentations:

Andrew Balbar, Ph. D.                      Duke University
Arthur Beaudet, M. D.                       Baylor College of Medicine, Houston
Richard Bertin, Ph.D.                        FDA, Orphan Products Development
Ned Bodamer, M.D.                         Institute of Child Health, England
Y. T. Chen, M.D.,Ph.D.                     Duke University
Janice Chow, M.D.                           National Institutes of Health
Blythe Devlin, Ph.D.                          Duke University
Robert Eanes, M.D., Ph.D. Stephen F. Austin University
Peter Healy, Ph.D.                            Mac Arthur Agricultural Institute, Australia
Rochelle Hirschhorn, M.D.              New York University
Maryann Hui, M.D., Ph. D.               New York University
Tateki Kikuchi, Ph. D.                      National Institute of Neuroscience, Japan
Frank Martiniuk, Ph.D.                      New York University
Ralph Nichols, Ph.D.                         National Institutes of Health
Paul Plotz, M.D.                                 National Institutes of Health
Nina Raben, M.D., Ph.D.                  National Institutes of Health
Arnold J.J. Reuser, Ph.D.                 Erasmus University, The Netherlands
James Sidbury, M.D.                        National Institutes of Health
Alfred E. Slonim, M.D.                      North Shore University Hospital, New York
Seiichi Tsujino, Ph.D.                       National Institute of Neuroscience, Japan
Ans van der Ploeg, M.D., Ph.D.      Erasmus University, The Netherlands
Johan Van Hove, M.D., Ph.D.          Duke University
Joseph Zaretsky, M.D., Ph.D,          National Institutes of Health

This will be a very informative gathering dealing with developments in enzyme and gene replacement therapy in Pompe Disease.  The MDA should be present for this meeting .......

Sincerely,
Randall H. House
President
AMDA

To:
Y. T. Chen, M.D., Ph. D.

Duke University Medical Center

Dear Dr. Chen:
Thank you for your February13 fax transmission to MDA Grants Coordinator Karen Mashburn acknowledging receipt of our February 9 response to your request for MDA support of your (AMDA's) March 21-22 (1996) symposium.  Again, we regret that MDA is not able to respond positively to your request for financial support ( $10,000!).

Also, an Association Board meeting scheduled for the same period as your meeting in March in which key members of MDA will participate precluded their attendance at your meeting (as per AMDA's and Dr. Chen's requests).  We do extend best wishes for a successful conference and would appreciate receiving any summary of the event that may be made available.

Very truly yours,

Ronald J. Schenkenberger
Director of Research &
Patient Services Administration

cc: Karen Mashburn-Grants Coordinator

Dear Mr. Moore,
.....Our organization AMDA, Acid Maltase Deficiency Association, has been in existence for 4 years.  We have sponsored 3 scientific conferences, the most recent of which was held at the NIH on December 3-5, 1998. It was attended by 60-70 scientists and/or physicians worldwide that are doing research in AMD or in closely related fields.

Early in the formation of AMDA, we talked with Dr. Norine Stirpe, Director of Research Development, at the Tucson office, about assisting us in sponsoring our first conference.  Dr. Y.T. Chen at Duke University sent Dr. Stripe information in our behalf supporting the organization of this first conference and also requesting partial sponsorship.  Our request for funding was denied. 

Letters were also sent to Ronald J. Schenkeuberger, Director of Research & Patient Services Administration and were copied to Karen Mashburn, Grants Coordinator.  These requests were also denied.  We sent an invitation to Karen Mashburn requesting that a representative of the MDA attend the March 1996 conference and make a presentation.  No response was made to our invitation.

We realize that MDA is a very large organization with many departments and that numerous small organizations such as AMDA make frequent requests for help. We are all grateful that such a monumental organization exists.....But sometimes small organizations such as AMDA can fill the gap, especially with rare and isolated diseases such as acid maltase deficiency, Pompe's disease.

AMDA maintains a patient registry in the US and also has patients registered in various countries throughout the world.  We send information and newsletters to patients, physicians, scientists, donors, other organizations, and friends/relative of patients throughout the world.  We have a website that supplies interested parties with updated information on research and links to other webs of interest.  We have funded research grants.....to various research groups.

In closing, I want to thank Dr. Reuser (Mr. Moore contacted Dr. Reuser about his work) ...and (you) for giving us the opportunity to contact you directly and to supply you with information about our organization. As you are aware, much progress has been made in the last 3-4 years, and we are anticipating the start of phase II clinical trials for ERT by the end of 1998 or early 1999.  We would like to think that AMDA has been instrumental in accelerating research in this field.  We.....would certainly welcome your cooperation and involvement with AMDA.

Best Regards,
Randall House
President, AMDA

>>Dear Marylyn,

Thanks for sending all these letters to GSDNET. I think it's important that people know how things go..... My conclusion is that without Dr. Reuser we wouldn't have come this far as we are now…..<<

____________________________________________________

To:

Marylyn House

Acid Maltase Deficiency Association

San Antonio, Texas

From:

Carol Sowell

Director of Publications

MDA

National Headquarters

Tucson, AZ

Dear Ms. House:

I’m writing in response to your emails of March 12, in which you take issue with our recent articles in Quest (March-April 2003) describing the success of enzyme replacement therapy (ERT) for Pompe’s disease.

Your imply that the main article exaggerates MDA’s commitment to research on Pompe’s disease/acid maltase deficiency, and that it omits important facts about the history of this research.  Both of these accusations are unfair and unwarranted.  Judging from documents attached to your letter, they stem from a long-held resentment over MDA’s decision not to participate in an AMDA-sponsored meeting in 1996. (see response below)

• “In the early days,” you say, “MDA was not as supportive of Pompe research as was suggested in the Quest article.” 

I’m not sure what you consider early days, but Pompe’s disease became part of our research and health care services program in 1976.  Since that time, we’ve spent more than $1.5 million on Pompe’s disease research. Much of that sum has gone to Yuan-Tsong Chen at Duke University in Durham, N. C., to support the pre-clinical development of ERT.  (see response below)

You claim that the article “overlooked…work done by the researchers in the Netherlands where the first clinical trials originated six months prior to Duke’s trials.”

On the contrary, beginning on page 17, the article states “…Chen began his first trial of enzyme replacement therapy for Pompe’s disease in 1999…(Genzyme) began testing enzyme replacement therapy for Pompe’s disease in 1998, through a joint venture with Pharming, a Dutch biotech company…” The article goes on to explain that Genzyme and Pharming were testing a form of the acid maltase enzyme that was different from Chen’s version, and that Genzyme eventually acquired the rights to the enzyme from Pharming.  (see response below)

Finally, I’d like to point out that the feedback to the quest article has been overwhelmingly positive.  In fact, Dr. Chen, who we note is a member of your scientific advisory board, reviewed and approved the article before it was published.  Also, the Unite Pompe Foundation has, with MDA’s permission, placed a link to the Quest article on its Web site. I hope that this letter clears up any misunderstanding, and that both our organizations can continue to focus on what’s really important—helping people with Pompe’s disease.  (see response below)

Sincerely,

Carol Sowell

Director of Publications

MDA

cc:  Daniel T. Stimson, Ph.D., Senior Science Writer (MDA)

       Ronald J. Schenkenberger, Director of Research Administration (MDA)

_____________________________________________________________

Dear Ms. Sowell:

Director of Publications

MDA

The following addresses your letter of March 17, 2003:

I do not dispute that Pompe's disease became part of the MDA's health care services program in1976 as you stated in your letter. After all, it is a muscle disease and thereby, rightfully should have received the attention of such a vast philanthropic organization as the MDA.

>>You stated, "Since that time (27 years), we've spent more than $1.5 million on Pompe's disease research." <<

Our interest in Pompe's disease started only eight years ago when our eleven year old daughter was diagnosed with this rare life-threatening disease. During the last eight years, we, too, have spent more than $1.5 (Over 4.9 Million!!) million funding research for Pompe's disease. This is vastly disproportionate funding between the MDA and AMDA (Randall and Marylyn House) considering the size of our two organizations and the number of years of our respective involvement. (AMDA-8 years;  MDA-27 years)

>>You stated, " Much of that sum has gone to Yuan-Tsong Chen at Duke University in Durham, N.C., to support the pre-clinical development of ERT."<<

We, also, supported Y.T. Chen's efforts during pre-clinical development of ERT.  In 1996, in addition to other funding at Duke, we financed the patent of Dr. Y.T. Chen's….invention entitled: "Tissue Specific Recombinant Human Lysosomal Acid Alpha-Glucosidase." ………. we did not retain royalties in this endeavor as is customary with some organizations.

>>You stated, "You (Marylyn House) claim that the article 'overlooked…work done by the researchers in the Netherlands where the first clinical trials originated six months prior to Duke's trials.' <<

>>You (Marylyn House) stated, "On the contrary, beginning on page 17, the article states "…Chen began his first trial of enzyme replacement therapy for Pompe's disease in 1999…(Genzyme) began testing enzyme replacement therapy for Pompe's disease in 1998, through a joint venture with Pharming, a Dutch biotech company…" The article goes on to explain that Genzyme and Pharming were testing a form of the acid maltase enzyme that was different from Chen's version, and that Genzyme eventually acquired the rights to the enzyme from Pharming."<<

Pardon me if I have misinterpreted this attempt to recognize the research efforts of the investigators in the Netherlands, but I feel that their contributions to enzyme replacement therapy for Pompe's disease deserves more than this succinct reference.

>>You state, "Finally, I'd like to point out that feedback to the Quest article has been overwhelmingly positive."<<

……… this is not a point of contention with us.  I only wish that the MDA had been more responsive to the needs of the Pompe community in the past seven years.  We, also, have had overwhelming response to initiatives that we have undertaken to spur a treatment for Pompe's disease.  Our most recent initiative was the publication of "The Physician's Guide to Pompe's Disease" ( http://www.rarediseases.org/nord/programs/freebooklets ) that we funded and distributed to over 15,000 physicians in the US.  This pamphlet is part of a series of NORD publications made available to physicians free of cost.

>>As you also stated in your letter,  "Judging from the document attached to your letter, they stem from a long-held resentment over MDA's decision not to participate in an AMDA-sponsored meeting in 1996." << (And two others!)

You are absolutely right.  I am resentful that the MDA rebuffed us.  I am also resentful that the physician/scientist at the Mayo Clinic that diagnosed Tiffany but would not even discuss her diagnosis with me (although, I was told, that there were less than 100 cases of this disease ever diagnosed).  I am also resentful of the pediatrician that told me that he hoped that I would find something wrong with Tiffany because I was so intensely concerned about her. I am also resentful of the orthopedic surgeon that so coldly addressed Tiffany about her prognosis for the future. I am also resentful of the pediatrician that implied that Tiffany had been sexually abused because her anal opening was enlarged. I am also resentful of a neurologist, urologist, proctologist, and pulmonary doctor that were all inept. There are more incidents that I could add to this list!

 
>>In closing you stated," I hope this letter clears up any misunderstanding, and that both our organizations can continue to focus on what's really important-helping people with Pompe's disease."<<

This is certainly the motivation of AMDA, and that is why we started this organization.  In 1995 there was little interest in this disease, and because of this lack of interest, we had little hope for Tiffany's future. We are more than thankful for the events that have transpired in the last 7-8 years. We only wish that things could have happened faster, so that Tiffany could still walk; so that Tiffany had more than 12-14% breathing capacity, so that Tiffany could have gone to high school and had friends and dated and enjoyed her teenage years. We wish that things had happened faster not only for Tiffany's sake but for the sake of the many patients and families that we have had contact with over the past eight years.  We would have welcomed MDA's involvement eight years ago, and we still do today. 

Better late than never!

Regards,
Marylyn House
AMDA

Dear Marylyn House:

Thanks for your response to my letter about Quest's story on Pompe's
disease. Both of our organizations can be proud of having a part in
advancing the research to the very promising level it has reached.

I don't have a relative with a neuromuscular disease but I've come to know
many families who are affected by the diseases in our program. So my heart
truly goes out to your family when I hear about the terrible treatment you
received from medical professionals. I've heard many such accounts from
people whose children have very rare diseases, and it's distressing to know
that families who are simply trying to help their kids still sometimes run
into such insensitivity.

At this point, I think the future is what matters. MDA is committed to
helping advance the research that offers new hope for a Pompe's treatment.
Our efforts -- and yours -- will someday deliver lifesaving results.

Sincerely,

Carol Sowell
Director of Publications
Muscular Dystrophy Association

Dear Ms. Sowell: