Unmet Clinical Needs, Scant Treatment Options for Angelman Patients Spotlighted in Review
The unmet clinical needs and general lack of treatment options for people with Angelman syndrome (AS) were the focus of a literature review, which also underscored the lack of research being conduced in people with this disease.
The study, “Unmet clinical needs and burden in Angelman syndrome: a review of the literature,” was recently published in Orphanet Journal of Rare Diseases.
AS is a rare neurodevelopmental disorder caused by a lack of expression of a specific protein, ubiquitin-protein ligase E3A (UBE3A), in the brain. Symptoms are multiple, and can include profound intellectual disability, lack of speech, difficulties with motor control and planning, sleep and behavior problems, and seizures.
But despite an understanding of the disease, there are no AS-specific treatments — a considerable burden for both patients and their caregivers.
Using electronic medical databases, the researchers documented the unmet clinical needs and quality of life impact of AS-associated symptoms. In particular, the team focused on movement, speech, behavioral, and sleep disorders, and identified studies that assessed treatment options for these symptoms.
In total, they identified 142 publications to include in their review; a number were case studies of a particular patient or patients.
Most AS patients suffer some form of motor impairment, but few studies examine different treatment options for efficacy, the review reports. Specifically, one case study showed that levodopa decreased tremor and other Parkinson’s-like symptoms in two adult patients. Another showed that intensive physiotherapy significantly improved gross motor function in a child with AS.
Only one placebo-controlled study was conducted into motor impairment, and it was non-conclusive on the role of the antibiotic minocycline in improving motor skills.
Physiotherapy is often suggested as an effective treatment option for AS patients, but no studies have been done to date to scientifically support and detail its possible benefits.
Next, the authors focused on speech. Many AS patients have only a few vocalizations and less than five words in their vocabulary.
Only one study looked at a treatment — minocycline — finding it could improve auditory comprehension but not expressive communication in children ages 4 to 12. Many approaches for oral speech studied focused on using alternative communication systems, such as hand symbols, picture symbols, or electronic devices. Parents and caregivers, however, noted a high burden in teaching these skills.
Behavioral symptoms are complex in AS, and difficult to treat. They can range from excessive smiling or laughing and hyperactivity, to autism-related symptoms, aggression, self-injury, and anxiety. One study of three children with AS showed that functional communication training, given individually, could lessen these behaviors. Another found intensive applied behavior analysis to be of no benefit.
Currently, no pharmaceutical treatments are known to ease behavioral symptoms in AS patients.
Another symptom commonly associated with AS is sleep disturbances. Studies have shown that AS patients have lower levels of melatonin, a finding that may explain why melatonin can improve sleep in some individuals. A placebo-controlled study showed that in six out of eight children, melatonin treatment decreased sleep latency (the length of time from full wakefulness to sleep), lowered the number of times a child work up during the night, and increased total sleep time.
This literature review highlights the severity of unmet clinical needs in AS, particularly the lack of approved treatments and clear guidelines for symptom-based interventions. Not only does this need affect patients, but caregivers also report high levels of fatigue and adverse quality of life.
“Given the likely high burden of AS, new treatments that target the etiology of the syndrome that result in even small improvements in features of the syndrome may be clinically and economically meaningful for patients and their families,” the researchers concluded.