Prader-Willi Syndrome and hypothalamic injury-induced obesity
Prader-Willi Syndrome (PWS) has a birth incidence rate of about 1:15,000. The syndrome mainly results from the loss of paternally-inherited chromosome region 15q11-q13 (the Prader-Willi Syndrome critical region). This defect results in damage to the hypothalamus - the homeostasis center in the brain that controls important functions such as hunger, sleep and body temperature. In PWS, there is an initial extreme hypotonia and failure to thrive, followed in early childhood by a marked preoccupation with food, leading to the hallmark symptom of hyperphagia (excessive appetite and inability to feel ‘full’) as well as disabling neuropsychiatric behaviors and disorders including temper outbursts, repetitive and ritualistic behaviors, rigid thinking, skin picking, depression, and psychosis in some cases.
Video credit: Foundation for Prader-Willi Research, (https://youtu.be/1FRSSQco_pk)
To learn about Prader-Willi Syndrome, please visit the websites of Foundation for Prader-Willi Research,
PWSA (USA) and International Prader-Willi Syndrome Organisation.
While PWS is caused by a genetic defect, the most common cause of hypothalamic injury-induced obesity is related to a rare non-cancerous tumor called a craniopharyngioma. When this tumor is removed, the hypothalamus can get damaged, leading to the symptoms of hypothalamic obesity. Other causes for hypothalamic obesity include other rare tumors, head trauma, and swelling in the brain. Patients share many symptoms with the PWS patients, including hyperphagia, rapid weight gain, low metabolic rate, and decreased physical activity. Similar to PWS, hypothalamic injury-induced obesity patients often suffer from neuropsychiatric disorders, including anxiety, depression, apathy, and OCD. An excellent recent review of hypothalamic injury-induced obesity is here. The Raymond A. Wood Foundation provides quality of life support for childhood brain tumor survivors and their families.
Please refer to the NIH GARD website for more information on PWS and of hypothalamic injury-induced obesity.
There is no effective or approved treatment for PWS or hypothalamic injury-induced obesity. Patients
and their loved ones are devastated by the lack of safe and effective therapeutic interventions.
As Parkinson’s disease (PD) progresses and the therapeutic window of L-Dopa reduces many patients experience dyskinesia (involuntary hyperkinetic movements). L-DOPA-induced dyskinesia (LID) is a motor complication that affects around 25-40% of Parkinson’s disease (PD) patients after 4-6 years of L-Dopa therapy, and increases thereafter, with prevalence especially high in young-onset PD. LID can be painful and severely disabling - causing fatigue, increased risk of falls/injuries, social withdrawal, reduced quality of life and increased burden on caregiver. LID is one of the most debilitating aspects of PD for many patients.
Currently, only amantadine is approved by the FDA for the treatment of dyskinesia, yet it is not efficacious for all patients. Furthermore, amantadine also presents risks of severe adverse effects such as hallucinations and tolerance to its effect.
The following short video provides an insight into how debilitating dyskinesia can be:
Video credit: Raymond A. Wood Foundation, (https://youtu.be/AVVjVKQB18I)
Video credit: Parkinson's UK (Can't Eat - Matt, dyskinesia and Parkinson's - YouTube)