Testifying: Daniel Paul Perez, President & CEO (Respectfully Submitted on April 1, 2005)

Organization: FacioScapuloHumeral Society, Incorporated (FSH Society, Inc.)

3 Westwood Road, Lexington, MA 02420 USA

(781) 860-0501 phone, (781) 860-0599 fax, e-mail: daniel.perez@fshsociety.org

Committee: United States Senate Appropriations Subcommittee on Labor, Health and Human Services and Education and Related Agencies

Regarding: FY2006 Appropriations for the National Institutes of Health (NIH) Research Programs on Facioscapulohumeral Muscular Dystrophy (FSHD).

STATEMENT OF DANIEL PAUL PEREZ, PRESIDENT & CEO, FACIOSCAPULOHUMERAL SOCIETY (THE FSH SOCIETY) REGARDING FISCAL YEAR 2006 APPROPRIATIONS FOR THE NIH RESEARCH PROGRAMS ON FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY (FSHD) APRIL 1, 2005

Mr. Chairman, it is a pleasure to submit this testimony to you today.

My name is Daniel Paul Perez, of Lexington, Massachusetts, and I am testifying as President & CEO, of the FacioScapuloHumeral Muscular Dystrophy Society (FSH Society, Inc.) and as an individual who has lived with facioscapulohumeral muscular dystrophy (FSHD) for nearly forty-three years. FSHD is the third most prevalent form of muscle disease. It affects 1/20,000 people. For men, women, and children the major consequence of inheriting FSHD is a lifelong progressive and severe loss of all skeletal muscles. Most people are familiar with Duchenne muscular dystrophy (DMD) that affects boys. What they are not aware of is, that in any given moment, there are probably more individuals with FSHD alive than with Duchenne MD (14,800 vs. 11,000). Recently, the NIH identified significant gaps in FSHD and a preponderance of DMD research grants and reported that it only has five (5) active projects on facioscapulohumeral muscular dystrophy in its entire NIH wide portfolio.

We have given testimony before the U.S. Congress every year since 1994. We have submitted 26 written testimonies and 5 oral testimonies to the U.S. Senate and U.S. House Appropriations Subcommittees on Labor, Health, Human Services and Education and Related Agencies. We have had considerable report language written in the appropriations budget from the committees directed to the National Institutes of Health (NIH) with regard to improving the portfolio at the NIH in FSHD in nearly every year that we have come before you. In April 2000, prior to the passage of the “Muscular Dystrophy CARE Act 2001” law, we testified that Congressional directive on FSHD has been and is repeatedly ignored by the NIH. Since 2001, we have been working closely with the NIH on the MD CARE ACT 2001 law mandated research plan. Prior to all of the activity around the MD CARE Act 2001, we noted then that the NIH is seriously out of compliance with the previous four years of Congressional Directives. Incredibly, today in the calendar year 2005 heading into the fiscal year 2006 the NIH still is out of compliance and has an anemic portfolio on FSHD. Going back in time, in 2000 we reported the NIH had not responded to the past and prior years of Report Language.

The Report Language for 2000 has been responded to in an untimely manner and mainly ignored. The 2000 Report Language is as follows: "The Committee is concerned that NIH has not responded to a previous request to develop a plan for enhancing NIH research into Facioscapulohumeral (FSH) disease. The Committee urges NIH to promptly convene a research planning conference and to establish a comprehensive portfolio into the causes, prevention, and treatment of FSH disease through all available mechanisms, as appropriate. The Director is requested to be prepared to testify on the status of this initiative at the fiscal year 2001 appropriations hearing." (House Report 3037, p. 81 for NINDS, p. 97 for NIAMS.). The status of Fiscal Year 2000 Report Language is as follows: FSHD extramural research is almost non-existent. Intramural research on FSHD is non-existent at NIH.

The Report Language for 1999 has been ignored and the status of the Report language for Fiscal Year 1999 is not done. The 1999 Report Language is as follows: "The Committee encourages the Institute to continue and expand research efforts focused on aiding in the diagnosis and treatment of FSHD." (House Report, NINDS Section, p. 103.), and, "The Committee was pleased with the Institute’s response to last year’s request which encouraged NIH to stimulate research in the area of facioscapulohumeral disease (FSHD). However, the Committee notes that NIAMS has not responded in developing a plan for enhancing FSHD research, and has not addressed the question of whether an intramural program in this area would be beneficial. Therefore, the Committee urges NIH to conduct a research planning conference in the near future in order to explore scientific opportunities in FSHD research, both intramurally and extramurally.” (House Report, NIAMS Section, p.120-121.) The status of 1999 Report Language is as follows: FSHD extramural research is almost non-existent. Intramural research on FSHD is non-existent at NIH.

The Report Language for 1998 has been ignored and the status of Report language for Fiscal Year 1998 is not done. The 1998 Report Language is as follows: "The Committee has heard compelling testimony about facioscapulohumeral (FSH) disease, which causes progressive and severe loss of skeletal muscle. FSHD research includes aspects such as molecular genetics, neurological function and muscular dystrophy involving multiple NIH Institutes. The Committee encourages NIH to take steps to stimulate research in this area and requests NIH to develop a plan for enhancing NIH research into FSH disease (FSHD), including an assessment of whether an intramural research program in this area would be beneficial." (House Report, p.101.) In 2005, the status of 1998 Report Language is as follows: FSHD extramural research is almost non-existent. Intramural research on FSHD is non-existent at NIH.

We have worked hard to be sure that our constituency understands and supports the doubling of the NIH budget and have been very successful in helping to grow the NIH budget from $10.326 billion to $28.649 billion. In the same period, we saw FSHD funding increase by about $1.3 million. This year we will spare you the heartache of our personal story and the pain and suffering our disease brings in its train. This year we simply would like you to ask the NIH “Where did the money that Congress appropriated and further directed through appropriations report language go?”

We formerly request a congressional investigation, hearing or some other Congressional action regarding the absolute failure of the NIH to increase funding in facioscapulohumeral muscular dystrophy (FSHD). We have been testifying and generating report language and laws for a dozen years and have done the yeoman’s share in building the base for FSHD. Despite the specific directions from the Congress in report language as shown above and with a public law and a federal advisory committee on muscular dystrophy, the NIH has failed to follow through on improving FSHD research. Despite our active involvement with the NIH, the NIH has made the grant review process very secretive, has turned down opportunities to shed light on the grant decision making process and still has not responded to congressional letters and inquiries on the lack of facioscapulohumeral muscular dystrophy (FSHD) research in the NIH portfolio.

I would like to illustrate what we have done at the FSH Society, Inc. to improve the funding and portfolio of muscular dystrophy (MD) and FSHD. The FSH Society (Society) has represented the FSHD community of researchers and clinicians by the following activities on the Hill, in the districts, and at the NIH. The FSH Society was the first on the Hill and at the NIH and before Parent Project Duchenne Muscular Dystrophy (PPDMD) and MDAUSA for many years since 1993. The Society has given nearly three dozen Congressional testimonies, in writing and in person, before the committee to support the doubling of the NIH budget and to encourage spending on muscular dystrophy. The Society has succeeded in achieving nearly a dozen sections of report language in appropriations reports. I have served on numerous NIH research and planning task forces. The Society has had countless hundreds of meetings with the Directors, Staff and program officers of the NIH NINDS, NIAMS, NICHD, NHGRI, ORD and the OD. I served on the five year long range planning meeting for the NIH NIAMS July 1999. I rewrote the MD CARE Act 2001 bills to include all muscular dystrophies, ages and genders, and to establish the Muscular Dystrophy Coordinating Committee (MDCC) federal advisory committee with public members, and to establish five national centers for MD not at the exclusion of the basic research, and much more. The Society has contributed to supporting two NIH funded FSHD research planning conferences (1997, 2000). I work closely and collaboratively with NIH program directors. I serve on the MDCC at the request of Secretary Tommy G. Thompson and Dr. Elias Zerhouni. I helped write the MDCC NIH research plan submitted to Congress in summer 2004. I continually encourage FSHD researchers to submit NIH grant applications for R01, R21, R03, P01, U54, K, T, F training and mentoring awards and Director’s Pioneer Awards. The Society has given testimony before the Institute of Medicine (IOM) on improving the Center for Scientific Review (CSR) grant review process for FSHD. The FSH Society itself has funded $1.1 million in $30,000 a year fellowships to more than 2 dozen researchers in 5 years, leading to nearly 7 dozen publications in top tier journals. The FSH Society helps the NIH FSHD patient registry and existing Wellstone Cooperative Research Center’s as a volunteer health agency.

As a grant agency, the FSH Society has world renowned and leading clinicians and researchers peer reviewing applications, funding research, reviewing progress reports and preliminary data and ideas. We know and have comprehension on the quality of applicants and projects and data being submitted to you in the NIH grant applications for FSHD research. I have first hand knowledge of the research as well as our Nobel quality advisors. I can tell you that researchers of Wellstone, Nobel, and Howard Hughes stature working on FSHD have had applications on FSHD rejected by the NIH. However, their applications on other types of muscular dystrophy have been funded by the very same agency.

Mr. Chairman, as you know, the National Institute of Child Health and Human Development (NICHD), the National Institute of Arthritis and Musculoskeletal Disorders (NIAMS), the National Institute of Neurological Disorders and Stroke (NINDS), and the National Human Genome Research Institute (NHGRI) are four of the National Institutes of Health (NIH) institutes called upon by the Muscular Dystrophy Community Assistance Research and Education Act of 2001 (MD CARE Act 2001) to develop a research plan for muscular dystrophy (MD) research and education conducted through the National Institutes of Health. Certainly, other NIH institutes will be called into action where appropriate such as NHLBI, NEI, NIA, NIMH, NCRR, FIC, and OD.

We rewrote the MD CARE Act 2001 bill from the Muscular Dystrophy Children’s Assistance Research and Education Act 2001, covering only the childhood form of`Duchenne MD (DMD), to the Muscular Dystrophy Community Assistance Research and Education Act 2001 covering all forms of MD. We rewrote the bill to include all forms of muscular dystrophy affecting men, women, and girls in addition to boys because it was the right thing to do. Oddly, in 2004 Duchenne MD received a commanding portion of the muscular dystrophy funding and seven of the other muscular dystrophy types have little or no funding from the NIH.

An analysis was presented at the December 2004 MD CARE Act mandated Muscular Dystrophy Coordinating Committee (MDCC) meeting of the 164 grants in the NIH portfolio for future planning purposes related to the five sections of the muscular dystrophy research plan. Subsequent to the meeting, I requested the details of the 164 grants used for the December 1, 2004 discussion from Dr. John Porter (DHHS NIH NINDS), the Executive Secretary of the MDCC. It is has been communicated that this compilation was done for planning purposes. From discussions with Dr. Porter we understand that this view of grants differs from the muscular dystrophy portfolios as presented by the budget and NIH OCPL offices regarding the various institutes along coding parameters. The 164 grants were assembled with a degree of scientific subjectivity and based on professional expertise and judgment. The December 2004 MDCC meeting yielded an analysis of a subjective grouping of the NIH wide 164 muscular dystrophy grants. Eight were reported related to FSHD. At that time, the NIH identified that 8 out of 164 grants are on FSHD! Only eight out of 164 grants are for research on FSHD the third most prevalent dystrophy that affects men, women and children!

The details of the data of the 164 grants as presented at the December 1, 2004 MDCC for the grants with funding start dates in 2004 shows 35 grants funded for the 2004 year to that date. The count by dystrophy for calendar year 2004 is: 18 for Duchenne muscular dystrophy (DMD), 2 for Limb Girdle muscular dystrophy (LGMD), 1 for Myotonic muscular dystrophy (DM), 1 for facioscapulohumeral muscular dystrophy (FSHD), 7 for stem cell research, and 6 for other research. To re-iterate by dystrophy the total grants awarded in 2004 were: 18 for DMD, 2 for LGMD, 1 for DM, and 1 for FSHD! The most recent year of funding data shows that the non-Duchenne muscular dystrophy group is not doing well in terms of numbers of grants and funding. We request a hearing that focuses on this issue with immediacy and attention to ameliorating this unequal growth. Oddly, there is an order of magnitude difference between Duchenne muscular dystrophy (DMD) and the entire complement of all other dystrophies.

What has happened in facioscapulohumeral muscular dystrophy (FSHD) research in the five years since the MD CARE Act was signed and what has happened since the thirteen years since we first started asking NIH to invest and build the facioscapulohumeral muscular dystrophy portfolio? NIH has rejected nearly four dozen grant applications on facioscapulohumeral muscular dystrophy of R03, R21, R01, P01, U54, NIH Director Pioneer Award Nominations mechanisms and more. The funding track record speaks for itself. To date in FY2005 the NIH has rejected every FSHD application it has received. It is difficult to attract investigators to FSHD when there is no money made available for them and it becomes a downward spiral to attract new and promising investigators.

Incredibly, the NIH NIAMS, NINDS, NICHD, NHGRI FSHD funding is still non existent. Since 2001, the overall NIH wide muscular dystrophy budget has increased from $21.0M to $42.2M in FY2006 estimated and enacted. Since 2001, the FSHD budget has increased from $500,000 to $1.6M in FY2006 estimated.

National Institutes of Health (NIH) Muscular Dystrophy and FSHD Appropriations History

Source: NIH/OD Budget Office & NIH OCPL

(Dollars in millions)

Fiscal Total NIH NIAMS NINDS NICHD NHGRI NIH wide

Year Dollars on MD Dollars on MD Dollars on MD Dollars on MD Dollars on MD Dollars on FSHD

2000 $12.6M $4.8M $4.9M $1.2M $0M $0.4M

2001 $21.0M $9.2M $8.2M $0.5M $0.3M $0.5M

2002 $27.6M $11.1M $9.8M $0.6M $2.3M $1.3M

2003 $39.1M $15.5M $13.2M $4.5M $2.1M $1.5M

2004 $38.7M $15.0M $14.8M $3.8M $0.3M $2.2M

2005ES $41.0M $16.3M $13.7M $4.8M $2.2M $1.6M

2005EN $42.2M $15.2M $16.6M $5.0M $0.3M $1.6M

2006ES $42.2M $15.2M $16.7M $5.0M $0.3M $1.6M

NIH NIAMS. The NIAMS is ostensibly the lead institute at the NIH on muscular dystrophy. After all of our efforts the NIH National Institute of Arthritis and Musculoskeletal Disorders (NIAMS) now has only one research contract that it is co-funding with NIH NINDS for FSHD for $186,233 per year? Not one single research grant for FSHD, the third most prevalent dystrophy! The total muscular dystrophy portfolio ending December 15, 2004 was 58 projects, including Wellstone Cooperative Research Centers (CRC) components for a total of $14,992,725.

NIH NINDS. The NINDS is the second largest NIH contributor towards muscular dystrophy research funding. The NIH National Institute of Neurological Disorders and Stroke (NINDS) now has three research grants, one research contract, and one-quarter of a Wellstone CRC for FSHD for a total of $1,386,620 in FY2004. The total muscular dystrophy FY2004 portfolio reported February 1, 2005 was 39 projects, including Wellstone CRC components for a total of $14,756,290.

NIH NICHD. The NICHD is third largest NIH contributor towards muscular dystrophy research funding. The NIH National Institute of Child Health and Human Development (NICHD) does not have a single research grant or project directly focused or covering FSHD, which is the third most prevalent dystrophy that affects both boys and girls. The total muscular dystrophy FY2004 portfolio reported December 1, 2004 was 15 projects, including Wellstone CRC components for a total of $3,837,633.

NIH NHGRI. The NHGRI is historically the fourth largest NIH contributor towards muscular dystrophy research funding. The NIH National Human Genome Research Institute (NHGRI) does not have a single research grant or project directly focused or covering FSHD. The total muscular dystrophy FY2004 portfolio reported on December 1, 2004 was 1 project (Z01-HG000215-02), including Wellstone CRC components for a total of $281,396. The project is Hereditary Inclusion Body Myopathy (HIBM) and HIBM is not a type of muscular dystrophy.

Astonishingly, the total NIH wide spending on muscular dystrophy decreased from $39.1 million (FY2003) to $38.7 million (FY2004). Something is wrong with this trend given the Appropriations Subcommittee’s interest in this area and the efforts of the patient and research communities to shore up and improve muscular dystrophy research.

National Institutes of Health (NIH) Appropriations History

Source: NIH/OD Budget Office & NIH OCPL

(Dollars in millions)

Fiscal NIH Overall MD Research MD % FSH Research FSHD % FSHD %

Year Dollars Dollars of NIH Dollars of MD of NIH

2000 $17,821M $12.6M 0.071% $0.4M 3.18% 0.0022%

2001 $20,458M $21.0M 0.103% $0.5M 2.38% 0.0024%

2002 $23,296M $27.6M 0.118% $1.3M 4.71% 0.0056%

2003 $27,067M $39.1M 0.144% $1.5M 3.83% 0.0055%

2004 $27,887M $38.7M 0.139% $2.2M 5.67% 0.0079%

2005E $28,495M $41.0M 0.144% $1.6M 3.90% 0.0056%

2006E $28,640M $42.2M 0.147% $1.6M 3.79% 0.0056%

The NIH NIAMS, NINDS, NICHD, NHGRI the four lead institutes on muscular dystrophy reported a combined total of 113 projects on muscular dystrophy totaling $33,869,044 in FY2004. Of that total amount facioscapulohumeral muscular dystrophy (FSHD) received $1,572,853 for three grants, one contract and one-quarter of a Wellstone CRC.

Looking at the three existing Wellstone Cooperative Research Centers (CRCs) the NIH NICHD is spending $1,631,994, the NIH NIAMS is spending $1,224,971, and the NIH NINDS is spending $1,462,151. Only one-quarter of the Wellstone CRC funded by the NIH NINDS specifically works on FSHD. One more Wellstone center is currently in the process of being funded and none of the work at the fourth Wellstone pertains to FSHD. Of $4,319,116 funded to the first three Wellstone CRCs, only $365,538 is directly titled for FSHD. Only 8.46 percent of the total Wellstone expenditure is being spent on the third most prevalent form of muscular dystrophy that affects both men and women.

Mr. Chairman, we are troubled by the NIH grant review process used for the Wellstone Center applications as NIH uses a review process that deviates from its rigorous adherence to stating that it funds projects of the highest scientific merit. The Wellstone applications are reviewed for scientific merit and then the entire score is adjusted upward or downward based on a “gestalt” or an impression. The NIH NIAMS extramural program director writes that as an “example, one or more of the research projects may have very high scientific merit but lack relevance or contribute little to the Center [Wellstone] as a whole; conversely, research projects with relatively lower scientific merit may provide necessary strengths to the other components of the Center, and make a major contribution to the Center as a whole.” This changing of the rules has not worked in the favor of FSHD research and in fact quite the opposite in round two of the Wellstone evaluations. We ask the committee to hold a hearing to more closely examine if scientific quality is abrogated by a more subjective review standard.

Mr. Chairman, we are asking you to inquire about the abysmal performance record in FSHD funding and FSHD oriented Wellstone CRCs by the NIH. Last, at the end of the day, we all recognize that simply not enough grants are being submitted by the extramural research community to the NIH. Note that the NIH has done nothing to date to specifically encourage or targeted to draw in FSHD research applications in five or six years. For most of FY2004, there was no active program announcement on the street in muscular dystrophy from the NIH giving researchers no obvious avenues or handles to submit basic research grants. Of course, researchers are not restricted from submitting applications and can always submit grants in the absence of a call for proposal but most look for a program announcement or call for applications as a signal of NIH interest. The NIH is certainly not receiving enough grants applications for FSHD, but it also manages to reject almost every one of the scarce few being submitted by the top FSHD researchers in the world. It can be said that the volunteer health agencies and extramural community of researchers have done everything in their power to grow the area of research and to promote new researchers and research projects. We have been very successful as shown above and need the NIH to capitalize on our success and investments. The NIH has recognized that there is a systemic problem and has even self-identified a significant gap as relates to FSHD, but it has not stated what and if anything it intends to do to ameliorate the unequal growth and opportunity for muscular dystrophies other than Duchenne muscular dystrophy.

At the December 2004 MD CARE Act mandated Muscular Dystrophy Coordinating Committee (MDCC) the staff and Director’s of the NIH admitted there was a problem in the gap with FSHD research. The follow-up has been deferred to programmatic staff and the implementation details of the pending muscular dystrophy research plan. The NIH did not say exactly when it would follow-up on funding new research in FSHD. The NIH has a history in FSHD of committing to address this issue and never following through. The two prior NIH sponsored research planning conferences on FSHD are an example. Only a minor fraction of the 2000 NIH planning conference research plan developed by the NIH has been implemented. At this point, we are unsure if the lack of FSHD research in the NIH portfolio is a problem of miscommunication or perhaps a more deliberate and calculated on the part of the NIH.

We also ask that Congress request an explanation from the program staff and Directors of the NIH NIAMS, NHGRI, OD and NICHD for the inability to do better in the area of FSHD despite repeated Congressional requests. We implore Congress to request the NIH to specifically build the research portfolio on FSHD through all available means, including re-issuing specific calls for research on FSHD at an accelerated rate, to make up for historical and present neglect.

Mr. Chairman, we trust your judgment on the matter before us. We believe the Committee should explore why muscular dystrophy in general and FSHD in particular has been left behind in the great rise in research support at the NIH. Frankly, we are extremely frustrated that amid a huge increase in funding and strong unambiguous expressions of Congressional support, the NIH commitment in facioscapulohumeral muscular dystrophy (FSHD) is so feeble. Mr. Chairman thanks to your extraordinary efforts, consideration and work in this area I have hope that we will find solutions and that hope keeps me going.

Mr. Chairman, again, thank you for providing this opportunity to testify before your Subcommittee.