The Therapeutic Role of Growth Hormone Replacement Therapy for Persons with Prader-Willi Syndrome Across the Life-Span

Barbara Y. Whitman^1*#,, Myers SE^1*#, Bekx, T^2*, Moerchen V^3*, Carrel A^2*, Allen D^2*, Mogul H^4#, Frey M^4#, Lee P^5#, Pinyard B^6#, Zipf W^6#

¹Department of Pediatrics, Saint Louis University, St. Louis, MO USA; ²Department of Pediatrics, University of Wisconsin, Madison, WI, USA; ³Department of Physical Therapy and Rehabilitative Science, University of Maryland School of Medicine, Baltimore, MD, USA; ⁴Department of Pediatrics, New York Medical College, Valhalla, NY, USA; ⁵Department of Pediatrics, University of California at Los Angeles, Los Angeles, CA, USA; ⁶Columbus, Ohio, USA    

*Infant study;  #Adult study

Although not curative, recombinant human growth hormone replacement therapy (rhGHRT) can alleviate many of the somatic morbidities associated with Prader-Willi syndrome (PWS).  The effects of rhGHRT in children with PWS include acceleration of linear height velocity, optimization of final adult height, increased lean mass, increased bone mineralization, improvements in strength and agility, and possible augmentation of dietary effects on weight control and body fat.  Following the initial studies of children ages four to sixteen years of age, at least two questions regarding opposite ends of the age spectrum emerged: (1) would earlier initiation of rhGHRT in infants and toddlers with PWS lessen body fat accumulation and hasten accrual of lean body mass, perhaps modifying the natural history of the disorder; and (2) could rhGHRT positively and safely alter the body composition abnormalities of adults with PWS previously naïve to rhGH or previously treated adults whose rhGH therapy had been discontinued for greater than one year.

To address the first question, 29 children with genetically confirmed PWS ages 4 to 37 months were enrolled in a 24 month long, two-site, controlled study of the effect of early administration of rhGHRT.  Randomization to rhGHRT therapy or control groups was performed in a 60:40 distribution.  The study rhGH, Genotropin®, was dosed at 1 mg/m²/day, as in our previous study.  Treated subjects caught up to the population mean for length, had decreased percent body fat, and accrued more lean body mass.  Further, after one year, the treated group demonstrated statistically significant gains in language, cognition and motor development when compared to untreated controls.

To address the second question, a four-site study seeks to enroll 40 genetically confirmed adults with PWS meeting inclusion criteria for growth hormone deficiency. Thirty-four of 37 adults tested to date have been enrolled in this study to conduct a 6-month, open-label trial of safety and efficacy of Genotropin® in PWS adults (following a 6-month dose optimization phase).  Change in body composition serves as the primary outcome (efficacy) measure. Preliminary 6-month analyses of baseline changes in total body weight, BMI, waist and hip circumference, lipids, and behavioral assessments administered monthly to parents and assistants of the study subjects) are in progress.

We will briefly review each of these studies and their implications for the use of rhGHRT in persons with PWS across the life span.

 Major support for both studies was provided by Pharmacia/Pfizer.

June 2004