#IARC2017 – EU Supporting Studies to Better Understand Natural History of SCAs
The European Union is supporting a number of projects focused on the natural history of several spinocerebellar ataxias, projects that look at disease course over time — from onset to resolution — in a person. A better understanding of SCAs natural history will offer insights into disease progression, markers of progression, and potentially open new avenues to therapies.
Thomas Klockgether with the German Center for Neurodegenerative Diseases (DZNE) and the Department of Neurology at the University of Bonn presented the study, “Natural history of the spinocerebellar ataxias (SCAs).” The presentation was part of Session 3, Natural History, Biomarkers and Endpoints, at IARC 2017, which runs through Sept. 30 in Pisa, Italy.
Spinocerebellar ataxias (SCAs) are a group of genetically and clinically heterogeneous disorders, and a clear need exists to characterize the natural history of these diseases and identify factors that contribute to disease progression.
Understanding the functional decline evident in patients with different SCAs, identifying factors that contribute to it, and establishing measurable markers able to assess clinical outcomes in trials are important steps to potential therapies.
The study, initiated in 2005 and running through 2050, has included 526 patients. Its primary goal is to determine ataxia severity, as measured by a newly developed and validated ataxia scale, the Scale for the Assessment and Rating of Ataxia (SARA).
SARA assesses several parameters with a cumulative score ranging between 0 (no ataxia) and 40 (severe ataxia).
Researchers observed that the extent of genetic mutations, age at onset, and disease duration were largely responsible for determining SARA scores in SCA1, SCA2, and SCA3 patients.
The annual SARA score increased by 2.11 in SCA1, 1.49 in SCA2, 1.56 in SCA3, and 0.80 in SCA6. In SCA1 patients, in particular, longer repeat expansions were associated with faster disease progression; in SCA2 patients, lower age at onset was seen to determine faster progression.
Furthermore, over an eight-year follow-up, “activities of daily living, quality of life and mood steadily deteriorated,” Klockgether said in his presentation. “There were no significant differences in the rate of deterioration between genotypes,” he added, although a trend showed fastest worsening in SCA1 and slowest in SCA6.
“In addition to SARA and repeat length, non-ataxia symptoms, in particular cognitive impairment and dysphagia [difficulty in swallowing] affected the outcome,” the team wrote in its study.
Researchers are currently conducting follow-up studies, including the ongoing European Spinocerebellar Ataxia Type 3/ Machado-Joseph Disease (ESMI), funded by the EU Joint Programme – Neurodegenerative Disease Research (JPND).
The ESMI study is investigating brain alterations in SCA3 patients, and trying to identify markers of disease progression. It includes seven European cohorts and one U.S. patient group, comprising about 900 SCA3 patients.
As part of the ESMI project, researchers created an SCA Registry that can be used for prospective evaluation of study participants. The registry contains data from the EUROSCA cohort, and allows data to be imported from other patient study groups.
Klockgether, however, emphasized that “it is questionable whether the European data [like EUROSCA data] are representative for patients in other world regions.”
So the goal is to establish a common and open database in SCAs available to clinical researchers worldwide.
“Intense worldwide collaboration in clinical SCA research is required,” Klockgether said on Thursday. “Europe and US-Europe collaboration is nice, but it is not enough.”
He also emphasized the need to “harmonize clinical assessment protocols, agree on common biobanking and imaging protocols, and improve training of investigators. This will allow to jointly acquire, exchange and analyze data.”
Concerning disease biomarkers, Klockgether believes that “the ideal marker would be a blood marker, which would allow blood samples worldwide” to be analyzed in a similar fashion.