The Effect of Growth Hormone Treatment on Premature Aging and Quality of Life in Adults with PWS

Funding Summary

In PWS individuals aged 40 and up, quality of life (QoL) seems to be mainly impaired by premature aging, and premature aging in PWS seems to be less prominent in adults treated with growth hormone (GH). This project will investigate whether GH indeed slows down premature aging in PWS, by using a large group of older adults in the Netherlands that have never before received GH treatment. In this project, we want to investigate aging at both the clinical and cellular level, including mobility, muscle strength, memory tasks, and cellular and DNA aging. This will increase understanding of the physical and cellular processes that cause premature aging in PWS, and if successful, making the case that GH should be treatment for adults with PWS worldwide. 

Lay Abstract

In the Dutch Center of Reference for PWS, we take care of 450 children and adults with PWS. Our experience with the adults is that the unlimited appetite is no longer the main problem in the ‘elderly’.  In PWS individuals aged 40 and up, quality of life (QoL) seems to be mainly impaired by the fact that their brain and body seem to get old much faster than one would expect based on their chronological age. This is called ‘premature aging’ and it seriously impairs QoL in adults with PWS. This premature aging seems to be less prominent in adults treated with Growth Hormone (GH) during childhood, which suggests that GH might be able to slow down this process. We want to investigate whether GH indeed slows down premature aging in PWS.  In the Netherlands, we have the unique situation that, since this year, GH will be reimbursed for all adults with PWS. This means that, from a patient care perspective, we are going to start GH in a large group of older adults who have never received GH treatment before (‘GH naïve’ individuals). This new situation gives us the ‘once-in-a-lifetime opportunity’ to assess the effect of GH treatment on aging in adults with PWS. Apart from the timing, the composition of the current research group is also unique. The project is a collaboration between three research groups that are worldwide leaders in the field of 1) genetic and developmental endocrinology 2) metabolism research and 3) translational research in aging and geriatrics. This means we have all the expertise to carry out this project successfully.  The unusually large size of our patient cohort makes it also feasible to perform this study. Of the 160 PWS adults we see in our center, over sixty patients are ‘GH naïve’. Although not all of them will be willing and able to use GH, we are convinced that it will be feasible to include at least 20-25 GH naïve patients. In this project, we want to investigate aging at both the clinical and cellular level. On one hand, we want to look at physical aging, like mobility, elasticity of heart and vessels, metabolism and brain function. We will measure muscle strength, vascular ‘stiffness’, levels of blood lipids and hormones (relevant to stay young and healthy) and memory tasks. On the other hand, we want to investigate whether cells and DNA also age prematurely in PWS, and what the effect of GH is on this cellular aging process. We will investigate this in the laboratory, by measuring DNA damage and other aging-related features. Our research will increase understanding of the physical and cellular processes that cause premature aging in PWS. 
On the short term (within 5 years), our research can help to show the effects of GH treatment on age-related health problems (and the associated decline in QoL). This can help us convince healthcare authorities to make GH standard treatment for adults with PWS worldwide.  At the longer term (after 5 years), the relevance of our study might also extend beyond the PWS community. When we can show that GH helps to slow down aging in adults with PWS, this will also increase understanding of aging in the general population, and the effects of GH on aging in non-PWS individuals.