[Congressional Record Volume 144, Number 82 (Monday, June 22, 1998)]
[Extensions of Remarks]
[Pages E1189-E1190]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]




IN SUPPORT OF ADDITIONAL FUNDING AND AWARENESS ABOUT POLYCYSTIC KIDNEY 
                                DISEASE

                                 ______
                                 

                           HON. JIM McDERMOTT

                             of washington

                    in the house of representatives

                         Monday, June 22, 1998

  Mr. McDERMOTT. Mr. Speaker, the Polycystic Kidney Research Foundation 
held a conference here on June 19-21. Four hundred patients, 
physicians, and researchers gathered to review the latest developments 
in research for a treatment and cure. Supporters visited members of the 
House and Senate to ask for a commitment to increased funding at the 
National Institutes of Health in research for this disease which 
affects 600,000 Americans. Polycystic Kidney Disease (PKD) is the most 
common life-threatening genetic disease and costs $1.5 billion yearly 
in Medicare funding. Scientists are hopeful that with increased funding 
in research the disease can be treated or cured within the next five 
years.
  Attached is an article which describes recent gains we've made in 
combatting PKD and how important continued research will be

[[Page E1190]]

to finding a cure. I urge my colleagues to take the time to read this 
article and learn more about this terrible disease.

         [From Contemporary Dialysis & Nephrology, Sept. 1997]

  Genetic Breakthroughs Take Center Stage in Accelerating Polycystic 
                          Kidney Disease Drama

                        (By Michael D. O'Neill)


                              introduction

       ``I believe the future holds the prospect of fundamental 
     breakthroughs that will allow us to develop treatments that 
     will change the basic biology of polycystic kidney disease 
     (PKD).''
       This hopeful message was delivered by Josephine Briggs, MD, 
     director of the Division of Kidney, Urologic, and Hematologic 
     Diseases in the National Institutes of Health's National 
     Institute of Diabetes and Digestive and Kidney Disease 
     (NIDDK), in her luncheon address at the 8th Annual Conference 
     on PKD, sponsored by the Polycystic Kidney Research (PKR) 
     Foundation, in Nashville, TN.
       In 1982, Joseph H. Bruening and Jared J. Grantham, MD, 
     founded the PKR Foundation to determine the cause, improve 
     clinical treatment, and discover a cure for PKD. Today, the 
     organization is the major funder of private PKD research 
     grants and the disseminators of information about the disease 
     worldwide to physicians, researchers, patients, and the 
     general public.
       Briggs' optimism was based on a continuing series of 
     dramatic discoveries related to the genetics and molecular 
     biology of PKD. These discoveries have come at an ever-
     increasing pace following identification of the PKD1 and PKD2 
     genes in 1994-1995 and 1996, respectively, and have roughly 
     paralleled an increasing rate of PKD-directed research 
     funding by both the NIH and the PKR Foundation.


                          ADDITIONAL ADVANCES

       Additional advances in the last few months have generated 
     even more excitement. Gregory Germino, MD, a nephrologist at 
     The Johns Hopkins University School of Medicine, Baltimore, 
     MD, has shown evidence that a two-hit mechanism initiates 
     cyst formation in PKD and suggested that intervention to 
     prevent the second hit may impact the course of the disease.
       Germino has shown that the normal PKD1 and PKD2 proteins 
     physically interact with each other in the cell membrane and 
     probably participate in a common cellular path way. This 
     finding may explain why defects in either of these genes, 
     located on different chromosomes, can cause the same clinical 
     disease.
       Briggs termed these discoveries ``enormous, dramatic, and, 
     in some cases, very surprising.'' She said that ``have 
     implications not only for PKD, but perhaps for other diseases 
     as well.''
       Germino described his findings at one of the conference's 
     many informative workshop sessions. Attendees also heard 
     encouraging news about the prognosis for children with 
     autosomal recessive PKD (ARPKD), and prenatal diagnosis of 
     ARPKD. They also received updates on numerous other areas of 
     PKD research and treatment.
       In her address, Briggs also commented on the future of 
     funding for PKD research and stressed the need for industry 
     involvement on the parts of both the biotech and 
     pharmaceutical industries.


                             PKD BACKGROUND

       PKD is a systemic disease. The most common problems are 
     associated with the kidneys, where fluid-filled cysts can 
     develop and lead to End-Stage Renal Disease (ESRD). As with 
     other forms of ESRD, dialysis and transplantation are the 
     available treatments.
       There are two major forms of PKD--the more common, 
     autosomal dominant (ADPKD) form that chiefly affects adults, 
     and the much rarer autosomal recessive (ARPKD) form that 
     affects children.
       ADPKD affects an estimated 600,000 people in the U.S. and 
     12.5 million around the world. It is said to be the most 
     common life-threatening genetic disease.
       In the US, over 1,000 people die each year from PKD, and an 
     additional 2,000 develop kidney-failure. Costs to US 
     taxpayers from dialysis, transplants, and treatment related 
     to this disease are estimated at more than $1 billion 
     annually.
       Defects in the PKD1 gene on chromosome 16 are responsible 
     for 85% of ADPKD while defects in the PKD2 gene on chromosome 
     4 are responsible for about 15%. A third gene (PKD3), which 
     has not yet been pinpointed, is defective in a small number 
     of ADPKD families. The gene for ARPKD has not yet been 
     identified, but it has been located within a small region of 
     chromosome 6.


                         THE TWO-HIT MECHANISM

       ADPKD patients are born with one defective PKD gene and one 
     functional PKD gene. For PKD1-associated ADPKD, Germino has 
     shown compelling evidence that cysts develop from a subset of 
     kidney cells in which both PKD1 genes are defective.
       Germino describes this as a two-hit mechanism. The first 
     hit is being born with one broken PKD1 gene. The second hit 
     is sustaining damage to the remaining functional PKD1 gene. 
     This second hit leaves the cell with no way to produce the 
     normal PKD1 protein, and that deficiency somehow leads to 
     cyst formation.
       This two-hit model is particularly attractive because it 
     offers an explanation for two-fundamental puzzles of PKD, 
     namely the highly variable course of the disease and the 
     focal nature of cyst formation (in PKD, only one out of every 
     100 or 1,000 nephron tubule cells actually goes on to become 
     a cyst--the vast majority of these cells are completely 
     normal).
       This argument proposes that the cysts develop only from 
     those cells that experience second hits and that the variable 
     disease course might be traceable to variable frequencies of 
     the second hits in different individuals.


                       CELL MEMBRANE INTERACTION

       The second dramatic finding, reported in the June 1997 
     issue of Nature Genetics, is that the normal PKD1 and PKD2 
     proteins interact in the cell membrane and probably work 
     together in a common cellular pathway. As noted earlier, this 
     finding may explain why defects in either of these genes can 
     cause the same clinical disease.
       ``By understanding pieces of this cellular pathway and the 
     steps involved, we hope that we can one day design safe and 
     effective therapies for PKD,'' Germino said.


                        HOPE FOR ARPKD PATIENTS

       Encouraging news concerning ARPKD was reported by Lisa 
     Guay-Woodford, MD, a pediatrician and assistant professor of 
     Medicine at the University of Alabama-Birmingham.
       ``Still, in 1997, there is a sense among the general 
     medical community that ARPKD is a universally fatal 
     disease,'' she remarked. ``The answer is that it is not. 
     While it's true that 30%-50% of these children will not 
     survive the newborn period, results from two recent studies 
     have shown that, if a child with ARPKD can survive the first 
     year of life, that child has a reasonably good prognosis.''
       Guay-Woodford said that, if sufficient family information 
     is available, it's possible to carry out prenatal diagnosis 
     for this disease, using DNA-based genetic linkage analysis. 
     With collaborators, Guay-Woodford has performed such 
     diagnoses in a number of cases where the fetus was known to 
     be at risk for ARPKD.


                          NIH AND PKD FUNDING

       In her luncheon address, Briggs stressed the urgent need 
     for the biotech and pharmaceutical industries to become more 
     involved in the funding of PKD research. She noted that the 
     estimated cost of taking a single drug to market is $270 
     million, which exceeds the entire NIH budget for kidney 
     disease research.
       ``If we are going to eventually see new drugs for PKD, we 
     also need pharmaceutical and biotech investment,'' she said.
       While noting that NIH funding for PKD research had 
     increased significantly--from $70,000 (one grant) in 1982 to 
     $7.3 million (46 grants) in 1996, Briggs, a nephrologist and 
     kidney researcher, expressed her desire for increased NIH 
     funding in the area of PKD research. The PKR Foundation has 
     previously stated that annual NIH funding for PKD research 
     has trailed allocations for diseases that affect fewer 
     people. Cystic fibrosis, for example affects 30,000 people in 
     the US and received $61 million in annual funding from the 
     NIH in 1996 while PKD affects 600,000 and received only $7.3 
     million.
       In 1996, the PKR Foundation funded $536,000 in PKD research 
     and will fund $750,000 by the end of this year.
       ``We directly fund individual investigators at major 
     teaching and research institutions and heavily promote the 
     need for increased PKD investigation at the federal level,'' 
     according to Dan Larson, PKR Foundation president. ``We plan 
     to work closely with Dr. Briggs and the appropriations 
     committees to add a zero to the current PKD research 
     allocation of $7.3 million.''

     

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