Treatment with methylprednisolone, an anti-inflammatory medication, had no evident benefit in children and adults with Friedreich’s ataxia (FA) enrolled in a pilot clinical trial conducted at the Children’s Hospital of Philadelphia (CHOP).
Oral therapy with methylprednisolone failed to improve patients’ overall mobility and neurological function, although three children significantly improved gait distance in one of the study’s assessments.
The study with the findings, “Open label Pilot Study of Oral Methylprednisolone for the Treatment of Patients with Friedreich Ataxia,” was published in the journal Muscle & Nerve.
Methylprednisolone is a corticosteroid that reduces inflammation and is used to treat various inflammatory conditions, including arthritis, lupus, ulcerative colitis, allergic disorders, and gland (endocrine) disorders.
The medicine also is believed to improve the symptoms of Friedreich’s ataxia, through either anti-inflammatory or metabolic effects. This has been supported by patient and caregiver reports noting improvements such as greater strength and walking ability, reduced fatigue, and higher quality of life.
The observed neuromuscular improvements are somehow identical to those of people with Duchenne muscular dystrophy (DMD), for whom corticosteroids are a standard of care, although it remains unknown exactly how they work.
Based on these observations, researchers at the Children’s Hospital of Philadelphia, supported by the Friedreich’s Ataxia Research Alliance (FARA), conducted a pilot, Phase 1 clinical trial (NCT02424435) to investigate whether oral methylprednisolone is safe and helps improve mobility and overall function of FA patients.
The study enrolled three children (ages 5–10) and eight adults (older than 45), all with genetically confirmed FA. In order to minimize risks and adverse events, researchers opted for a pulse dosing regimen previously tried in some patients.
Participants took 8-mg tablets of methylprednisolone over 28-day cycles. On day 1, participants started on a maximum dose of 48 mg, tapering thereafter by 8 mg each day across six days. Following this period, subjects were off medication for 22 days. The same treatment cycle was repeated across 24 weeks (six months).
To address change in patients’ neuromuscular function, researchers measured several performance scores at the study’s start and compared them with a follow-up 26 weeks after.
Overall, the results revealed that neurological abilities “improved minimally” following methylprednisolone treatment, researchers stated.
The study did not meet its primary objective; patients had no significant changes in timed 25-foot walk test (T25FW) scores, a mobility and leg function test, from the study’s start to 26 weeks of follow-up.
However, at 26 weeks, children walked significantly longer distances during the 1-minute walk test (1MW), reaching a maximum change of 30% compared with the study’s start.
“Although the change in 1MW could represent placebo or practice effects, such effects in timed walks have been minimal in similar [patient groups],” researchers said. “This suggests that the effects noted here might represent biological improvement” and that 1MW score may be a sensitive outcome measure for future studies in FA.
In general, there was a tendency toward greater changes in younger patients, which researchers interpreted as a result of age-related disease features, different responsiveness in children, or the relatively lower methylprednisolone dose in older patients (lower dose per weight).
Additionally, no changes were noted in quality of life, fatigue, and impact on daily activities reported by patients, as well as patients’ and clinicians’ global assessments regarding disease symptoms.
Levels of frataxin, the protein deficient in people with FA, also remained unchanged throughout the study.
Overall, methylprednisolone was well-tolerated, suggesting it may be helpful for some children with FA, provided a benefit is clearly demonstrated in future studies.
“Should methylprednisolone be considered as a treatment option, the side effects associated with long-term steroid use must be considered and may make such therapy contraindicated in some individuals,” researchers said.
Regimens such as pulse dosing may minimize such effects, although individuals on prolonged steroid treatment should have routine check-ups, particularly for bone mass loss, which may be particularly serious in FA patients.
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