Research must begin with understanding a disease’s impact on the people who have it

December 3, 2021

At the 2021 WORLD Symposium on Lysosomal  Diseases, Dr. Cara O’Neill presented the results of the Cure Sanfilippo Foundation-supported research study, “Parent experiences of Sanfilippo Syndrome Impact and Unmet Treatment Needs: A Qualitative Assessment,” published in the journal Neurological Therapy.

At the February conference, Dr. Cara O’Neill presented the latest research on the personal needs and desires of Sanfilippo Syndrome families and patients. The study was developed in response to the issues raised by many experts in the area that “most research questions are posed from a medical or regulatory perspective,” and they are often “removed from the true needs of patients,” said O’Neill.

Additionally, “It is clear you have to start with an understanding of the impact of the disease on the people who have it. Also, what they would value most in terms of alleviation before you set up a measurement … to be truly patient focused.”

The study was done in support of FDA guidelines for new treatment development research and was fully approved by all appropriate oversite reviewers. Data was gathered by questionnaire and multiple seminars from 25 parents of Sanfilippo patients with focus on exploring caregiver burden, symptoms with greatest impact, and meaningful and unmet treatment needs.

The study results identified two major areas of unmet needs: 1) cognitive/behavioral/psychological impact and 2) physical health impact. Under each area multiple major sub issues and needs were identified.

Cognitive/Behavioral/Psychological Impact Areas:

Communication and Relationships

  1. Parents reported that their child’s communications limitations in expression, pragmatic, and receptive language skills were significant burdens.
  2. Many parents noted that their inability to understand their children’s verbal and non-verbal messages caused a sense of helplessness, frustration, and distress.
  3. Some parents reported that their child’s ability to engage in any form of reciprocal communication was important to maintaining relationships and that even modest enhancement of interactions such as meaningful eye blinking or eye gaze would provide considerable benefit.

Frustration, Hyperactivity, Impulse Control and Aggressive Behaviors

  1. Parents experienced considerable caregiver burden due to problem behaviors not easily explained.
  2. These behaviors were noted to be associated with cognitive decline.
  3. These behaviors largely resolved as disease progressed to the later stages of the disease.

 Unsafe Behaviors

  1. Parents reported past and current need to be constantly watchful of child’s wellbeing.
  2. Safety concerns were primarily associated with symptoms of hyperactivity and impulse control.
  3. Caregivers as a result experienced considerable burden on themselves and family members associated with chronically maintaining this high level of vigilance.
  4. Parents of children with advanced disease experienced decreased concerns in the regard as decreased mobility and function resulted in decreased unsafe behaviors.


  1. Parents experienced increasing distress from seeing their child unhappy and anxious
  2. Patient’s anxiety associated with change or new experiences was particularly burdensome for families in day-to-day life.
  3. In later stages of disease progression, parents related that anxiety symptoms had either resolved or were no longer discernable to caregiver

 Sleep Disturbance/Nighttime Awakening

  1. Sleep disturbances were a commonly-recognized symptom for patients and caused parents to have inadequate sleep impacting parents’ day-to-day functioning
  2. Key issues are toileting and clean up, patient anxiety, and self-harm

Physical Health Impact Areas:

Pain and Its Management

  1. Patients almost universally experienced pain frequently, until late in the disease,
  2. Major problem due to communication issues making identifying source and cause of pain..
  3. The most-common source of pain for many patients is headache.
  4. Verbal and physical outbursts are frequently associated with painful episodes.


  1. Children in the mid-stage of Sanfilippo develop mobility challenges which is a major cause of patient and caregiver frustration and impacts activities of daily living.
  2. Increased burden on caregivers as a result.
  3. Reduced concern about safety due to reduction in child’s ability to engage in negative behaviors

Sleep Issues

  1. Problems seen in almost all patients, but occurrence seen most with stage of the disease.
  2. Patient sleep problems associated with behavior and more health problems.

Frequent Illness, Vulnerability to Illness, and Seizures

Nutrition, Feeding and Toileting

  1. Challenges with feeding and maintaining adequate nutrition for patient.
  2. Feeding and nutrition problems progress with level of disease.
  3. Caregiver and family impact due to great time commitment associated with eating and toileting limiting other activities for the family.
  4. Toileting challenges occur frequently over the entire disease evolution.
  5. Although toileting impact on patient was limited, caregiver, and family experienced considerable impact.

This study showed that parents agreed that cognitive functioning was an overarching element to many of the symptoms identified as problematic, but should not be the exclusive treatment target for Sanfilippo Syndrome. Further, if a treatment became available that was not able to alter cognitive ability, but would positively impact other physical aspects of the disease, this would still be a highly-desired treatment option.

There was overwhelming agreement among the study’s patient caregivers that maintenance of the child’s current level of function was a highly-acceptable outcome, as would be the maintenance of their current skill set or experience a slower rate of decline. The concept of tolerance for risky treatments or procedures emerged during the discussion around treatment; there was strong support and willingness among most participants to ‘‘try anything’’ for even a modest improvement in their child’s symptoms.

Most parents identified considerable personal disease impact and caregiver burden as a result of their children having Sanfilippo. Symptoms relating to expressive communication, problematic behaviors, mobility, and pain were most universally identified as the most significant unmet treatment need. In addition, parents advocated for clinical trials that address measures, in addition to cognitive, that improve mobility or treat pain management would be meaningful.

Most parents in the study expressed hopefulness related to their children’s lives, which has been associated with positive coping and adaptation to an uncertain future

“The data from this study provides critical insight into parents’ treatment priorities and impact of various disease manifestations that can be used to guide the selection of outcome measures in clinical trials, symptom targets for future therapeutic development, and regulatory decision-making,” said Glenn O’Neill, President of Cure Sanfilippo Foundation. “The findings need to be appreciated and included in future research.”

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