We will be posting a series of summaries from our 2015 researcher meeting, highlighting some of the most interesting new developments and discoveries presented there. This update covers a session on clinical research and outcome measures. The session was moderated by Thomas Crawford, MD.
Clinical Research Studies and Outcome Measures
This session started off with two talks discussing the patient perspective in SMA. First, Ying Qian of the SMA Foundation discussed a collaborative project between the SMA Foundation, Cure SMA, and Biogen to explore experiences of individuals and families affected by SMA. The primary goal was to hear the views of the 96 participants in their own words. She reported on thematic areas for four domains:
The Diagnostic Journey. Families reported substantial delays in arriving at a diagnosis. Three factors contributed to delays:
- Lack of awareness and knowledge about SMA;
- The difficulty of distinguishing normal from abnormal development in infants; and
- The challenge of differential diagnosis. “Differential diagnosis” is the process of distinguishing SMA from other conditions that have similar symptoms.
Newborn Screening. Parents generally held positive views about adding SMA to newborn screening panels. For example, it would:
- Enable earlier access to care;
- Shorten the diagnostic journey; and
- Give families more time to prepare to care for a disabled child.
The Psychosocial Impact of Living with SMA. Ten thematic areas characterized the impact:
- Confronting premature death;
- Making difficult treatment choices;
- Fearing the loss of functional ability;
- Coming to terms with lost expectations;
- Fatigue and stress;
- Limitations on social activities;
- Uncertainty and helplessness; and
- Family finances.
Meaningful Change. The significance of meaningful, beneficial change depended on where an individual was on the functional spectrum. Changes in motor function, however small, could have important implications for quality of life and independence. The participants said that items on the Expanded Hammersmith Functional Motor Scale (HFSME), a scale developed to measure motor ability in children with SMA, accurately reflected features of SMA types II and III. However, they noted that other aspects of SMA, such as respiratory function and fatigue, should also be assessed.
Next, Dr. Chad Heatwole from the University of Rochester spoke on patient-identified disease burden in adult SMA. In his study, Dr. Heatwole used interviews with adult SMA patients to identify the issues and symptoms that create the greatest disease-burden in this population. He conducted interviews with 15 adults with genetically confirmed SMA. Participants were ages 18 to 59. Five participants had SMA type II, while 10 had SMA type III.
Participants were asked to identify the symptoms and issues that have the greatest impact on their lives. 176 potential symptoms of importance to adult SMA participants were identified. Participants most frequently identified: difficulty performing activities related to personal hygiene, difficulty dressing, impaired walking, decreased independence, a decreased ability to carry a heavy load with arms, difficulty holding a pen, an increased reliance on family members, arm weakness, and difficulty feeding oneself as issues with the greatest impact on their lives.
This session closed with two talks on natural history studies in SMA to better understand disease progression in SMA Type II/III and Type I patients respectively. Natural history studies follow a group of individuals—in this case, SMA patients—over a period of time.
Dr. Richard Finkel discussed a study that provides the largest dataset of longitudinal data reported so far in patients with SMA type I and III. The aim of the study was to establish 12 month changes using the HFSME in a large cohort of ambulant (able to walk) and non ambulant (not able to walk) patients, to identify possible patterns of disease progression, and to determine the possible effect of different variables, such as gender, baseline values or age.
Of the 268 patients in the study who were between the ages of 2.5 and 55 years, 206 (76.86%) had changes between -2 and + 2 points on the scale. 12-month change was not associated with age in ambulant patients, while it was significantly different in different age groups in non-ambulant patients. For instance, those with SMA type II under five were the most likely to gain more than two points on the scale over 12 months, while those between 5 and 15 were most likely to show a decline of more than two points (about 20%). Decline was associated with: 1) onset of puberty, 2) weight gain, 3) contractures, and 4) scoliosis.
The final talk of the session was given by Dr. Stephen Kolb of Ohio State University on the Initial results from the NeuroNEXT SMA infant biomarker study. This is a study to characterize natural history and biomarkers in infants with spinal muscular atrophy (SMA) and healthy infants in a control group. Infants with genetically confirmed SMA and healthy infants were enrolled prior to 6 months of age and followed serially for up to 24 months.
The study was conducted at fifteen study sites of the NINDS NeuroNEXT Clinical Trial Network. Enrollment began November 2012 and ended September 2014 with 26 SMA infants and 27 healthy infants enrolled. Average age at enrollment visit was (mean±SD) 3.7±1.7 months for the SMA cohort and 3.3±2.0 months for the control cohort. Birth weight and length, gender distribution, ethnicity and gestational ages were equivalent in the SMA and control cohorts.
The NeuroNEXT SMA Biomarker Study exceeded enrollment targets and continues to have excellent retention of subjects. The SMA and control cohorts are well matched and can be expected to provide important longitudinal natural history data at the completion of this study. SMA infants demonstrate significant reductions in motor function (TIMPSI and CHOP-INTEND) and reduction in CMAP amplitudes at their first study visit. EIM, a non-invasive technique for the assessment of muscle health, is able to distinguish between SMA and healthy infants.
Pictured above: Presenter Stephen Kolb shares his research at our Family Friendly Poster Session.