Muscle MRI Captures Spinraza’s Effects on Tissue Fibers in Type 3 Brothers

Muscle MRI Captures Spinraza’s Effects on Tissue Fibers in Type 3 Brothers
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A newer imaging technique called diffusion tensor imaging (DTI) — a type of muscle MRI — is able to identify small changes in muscle architecture, and may be useful in monitoring the effects of spinal muscular atrophy (SMA) treatments like Spinraza (nusinersen) over time, a small study reported.

DTI used on two adults brothers, both with SMA type 3b and being treated with Spinraza, captured positive changes in tissue microstructure — the number, length, and organization of muscle fibers — in these men that reflected the stabilization in their disease over two years of treatment.

The study, “Muscle MRI in two SMA patients on nusinersen treatment: A two years follow-up,” was published in the Journal of the Neurological Sciences.

Spinraza, by Biogen, is the first disease-modifying treatment for infants and adults with different forms of SMA, and in wide global use. The company reports it is approved in more than 50 countries.

Among older patients, studies support the therapy being able to stabilize, and possibly improve, motor function.

“However, there are still some critical issues in understanding results in adults, including the lack of natural history data and outcome measures to monitor disease progression,” the researchers wrote.

Muscle MRI is coming into more frequent use for monitoring disease progression and treatment effects in various neuromuscular disorders. But SMA studies of adult patients still rely heavily on qualitative assessments and motor function scales in assessing treatment benefits.

Investigators in Italy did an “exploratory” study of whether DTI, an MRI-based imaging technique that uses water diffusion to evaluate tissue architecture, might be useful in monitoring changes with Spinraza use in adults over time. DTI is sensitive, but “traditionally used mainly for fiber tracking in the central nervous system,” the researchers wrote.

They evaluated two brothers, ages 47 and 45, with SMA type 3b whose symptoms first appeared  in adolescence. Both men’s upper limb function (like ability to lift and use hands) was assessed using the Revised Upper Limb Module (RULM), while lower limb function (ability to sit independently, or roll to one side) was measured via the Hammersmith Function Motor Scale Expanded (HFMSE).

Both underwent a full body muscle MRI at the study’s start (a baseline measure), and again at 10 and 24 months (two years) of Spinraza treatment.

The older man started with symptoms like falling and difficulty climbing stairs between the ages of 12 and 13. He began needing a wheelchair for longer distances at age 42, walking short distances with aid. Regular intrathecal (spinal canal) injection treatments of Spinraza started when he was  45.

Symptoms began for the younger brother between the ages of 13a and 14, and also included frequent falls, and difficulty climbing stairs. His symptoms worsen in adulthood, and he became wheelchair-bound at age 30. By 41, he needed help with most daily life activities. He started treatment with Spinraza when he was 43.

After two years of Spinraza’s use, both men achieved stability in their RULM and HFMSE scores.

“As a notable early finding, the [first] patient reported subjective improvement of his muscular endurance; regarding the functional scales after 10 and 24 months of treatment, RULM and HFMSE scores have remained stable over time,” the researchers wrote.

The younger patient, likewise, “reported subjective stability on motor function” and “functional … RULM scores have remained stable while HFMSE score decreased slightly” between months 10 and 24, they noted, adding that he “had to interrupt physiotherapy due to the COVID-19 pandemic.”

Baseline whole body muscle MRI scans showed a large portion of muscle tissue replaced by fatty tissue in the thighs and pelvis of both patients. This finding remained unchanged over the two years of treatment.

Analyses of DTI sequences performed 10 months after each man started with Spinraza, however, showed increases in the number, length, and organization of muscle fibers over these month. Changes seen remained stable at a DTI re-evaluation at two years of treatment.

These results further suggest Spinraza can stabilize disease course in older patients, treated years after symptom onset but with a milder SMA subtype and slower progression, the researchers reported.

These findings “suggest further evidence” supporting Spinraza’s use in “stabilizing disease course in adult SMA patients,” the researchers wrote.

Specifically, treatment “may have a positive effect on size, length and organization of fiber tracts raising the potential neurogenic rescue [nerve cell restoration] even in long-standing chronic SMA patients,” they wrote.

But they cautioned that these findings of DTI responsiveness come from a two-person study, further limited to “a SMA type 3 phenotype with slow progression.” As such, results “do not allow to establish whether this technique will correlate to disease progression and clinical findings,” and they “cannot be generalized to all SMA subtypes.”

Still, muscle DTI imaging “seems to play an interesting role to monitor treatment effects over time in adult SMA patients,” the team concluded.

Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.
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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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