Probiotic Treatment for Prader-Willi Syndrome

A whole new research area studying the function of intestinal microorganisms, also known as gut microbiota, has emerged during the last decade. As a result, dietary supplementation with specific bacteria (or probiotics) holds great promise as a therapeutic strategy for a wide range of diseases, from obesity to anxiety and depression, all of which are major characteristics of Prader-Willi syndrome (PWS). The main objective of the current proposal is to determine the effects of Bifidobacterium animalis subsp. lactis (strain BPL1) supplementation in children and young adults with PWS. Specifically, participants will receive placebo or BPL1 for 6 months, and then this phase will be followed by a 6-month extension period in which all participants will receive BPL1. This study will allow us to 1) determine the effects on fat mass and glucose metabolism; and 2) explore the effects on mental health symptoms by studying potential structural changes in the brain by magnetic resonance imaging (MRI) as well as using a number of psychiatric questionnaires.

Weight and height will be combined to calculate changes in BMI and BMI z scores from all subjects will be assessed

Fasting blood glucose and insulin concentrations will be combined to calculate HOMA-IR (Homeostatic Model Assessment for Insulin Resistance).

Measured by the validated Hyperphagia Questionnaire for Clinical Trials (HQ-CT), specific for subjects with Prader-Willi syndrome (scale 0-36, higher values indicate higher degree of hiperphagia). Parental or caregiver reported.

The Aberrant Behavior Checklist (ABC) is a 58-item questionnaire. It consists of five subscales: hyperactivity (0-48), lethargy (0-48), stereotypical behavior (0-21), irritability (0-45), and inappropriate speech (0-12). Higher scores indicate worse outcome. Parental or caregiver reported.

The Repetitive Behavior Scale (RBS) measures repetitive behaviors that are related to autism. It consists of 43-items grouped in two different scores: higher-order (ritualistic, sameness, compulsive and restricted subscales; score 0-87) and lower-order (stereotypy and self-injury; score 0-42) repetitive behaviors. Higher scores indicate worse outcome. Parental or caregiver reported.

Measured by the validated Social Responsiveness Scale (SRS-2) which assesses autism-related symptoms focusing on social function. Higher values indicate worse outcome. A total score of 76 or higher is considered severe; a score between 66 and 75 is considered moderate; a score between 60 and 65 is considered mild; a score of 59 or lower is considered within normal limits. Parental or caregiver reported.

Measured by the validated Clinical Global Impression Scale (CGI, scale 0-14, higher values indicate worse outcome). This toll will be completed by the clinician.

DNA isolated from fecal samples will be analyzed by sequencing the hypervariable region of the bacterial 16S gene.

Liquid chromatography coupled to mass spectrometry will be used to obtain a comprehensive metabolic profile of plasma samples

Subjects older that 12 years of age will undergo brain magnetic resonance imaging (MRI). Changes in orbitofrontal cortex, amygdala, hypothalamus, and total gray matter volume will be evaluated.

Inclusion Criteria: Diagnosed with Prader-Willi Syndrome with genetic confirmation On a stable diet and medication regimen for at least the last two months before enrollment Exclusion Criteria: Current enrollment in or discontinuation within the last 30 days from a clinical trial Patients with bariatric surgery in the last two years Patients with Type 2 Diabetes on insulin therapy Presence of other medical problems that would preclude study participation Unsuitable for inclusion in the study in the opinion of the investigator