Friedreich Ataxia Treatment & Management

Updated: Jul 14, 2016
  • Author: Jasvinder Chawla, MD, MBA; Chief Editor: Selim R Benbadis, MD  more...
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Treatment

Medical Care

The results of treating ataxia in Friedreich ataxia (FA) have generally been disappointing. No therapeutic measures are known to alter the natural history of the neurological disease. Standard treatment is administered for heart failure, arrhythmias, and diabetes mellitus.

High-dose propranolol has been described in a case report by Kosutic with reduction in thickness of the septal and posterior left ventricular walls and with complete normalization of diffuse electrocardiographic repolarization abnormalities. [11]

Li and colleagues have shown that therapeutic efforts should focus on an approach that combines iron removal from mitochondria with a treatment that increases cytosolic iron levels to maximize residual frataxin expression in patients with FA. [12]

The other therapies that have been used are as follows:

5-Hydroxytryptophan

5-Hydroxytryptophan is a serotonin precursor that has been used for a decade or more by Trouillas et al to treat various forms of ataxia with mixed results. [13] This drug was known to suppress posthypoxic action myoclonus. The rationale for use of the drug in FA was that FA may in part be due to a cerebellar deficiency of serotonin.

The results of a double-blind, cross-over study by Trouillas et al demonstrated that the levorotatory form of 5-hydroxytryptophan was able to significantly modify the cerebellar symptoms in patients with FA; however, the effect was only partial and not clinically major. [13]

A study by Wessel demonstrated stabilization of posture in patients receiving long-term treatment with 5-hydroxytryptophan and a clear deterioration in patients who did not receive the treatment. This form of treatment requires further study.

Coenzyme Q

Coenzyme Q is an antioxidant that can buffer free radical formation that is induced by excess mitochondrial iron. A combined coenzyme Q (400 mg/d) and vitamin E (2100 IU/d) therapy has been used in a study of 10 patients with slowing of the progression of certain clinical features and a significant improvement in cardiac function.

Experimental studies are underway to evaluate the use of coenzyme Q derivatives in limiting the toxicity of iron to mitochondrial structures.

Idebenone

Idebenone has been used as therapy for Friedreich ataxia for more than a decade. At present, several studies have assessed the influence of therapy on neurologic or cardiac function.

The effect of intermediate-dose idebenone (20 mg/kg/d) on quality of life and neurologic function was assessed in a recent study by Brandsema et al. [14] The Pediatric Quality of Life Inventory, the International Cooperative Ataxia Rating Scale, and an Activities of Daily Living Scale before initiation of idebenone therapy and after 1 year of therapy were assessed.

  • The scores on the Pediatric Quality of Life Inventory were universally worse after 1 year and correlated with decreased activities of daily living scores. However, there was a trend toward improved total, emotional, social, and school components of quality of life scores after 1 year of idebenone therapy.

  • There was no statistically significant change in Pediatric Quality of Life Inventory scores between baseline and 1 year of idebenone therapy. Functional ability, as measured by activities of daily living scores, seems to have the most influence on the physical quality of life.

  • Co-enzyme Q10 and idebenone were recently reviewed once again by Parkinson et al in 2013. [15] Prior randomized, double-blind, placebo-controlled intervention trial by Lynch et al did not reveal any statistically significant difference between the placebo and idebenone on the International Cooperative Ataxia Rating Scale. [16]

Tomassini et al (2012) have revealed that in vivo treatment with interferon-gamma increases frataxin expression in dorsal root ganglia neurons, prevents their pathological changes, and ameliorates the sensorimotor performance in FA mice. These results disclose new roles for interferon-gamma in cellular metabolism and have direct implications for the treatment of FA. [17]

Pandolfo et al have recently reviewed the utility of deferiprone with specific regard to its iron chelating properties and clinical benefits. [18]

In a study done by Elincx-Benizri et al, the authors presented their experience of 5 FA patients treated with deferiprone (20 mg/kg/day), in addition to idebenone treatment, followed over a period of 10-24 months, under off-label authorization. The authors concluded that combination therapy of a low dose of deferiprone with idebenone is relatively safe and might improve neurological function and heart hypertrophy. [54] However, future studies are needed.

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Surgical Care

Apart from surgery for scoliosis and foot deformities that may be helpful in selected cases, no significant surgical treatment is available for Friedreich ataxia. A study from Milbrandt and colleagues emphasized that in scoliosis braces were seldom effective and that segmental constructs are effective in creating substantial intraoperative correction and maintaining correction postoperatively. [19]

In addition, heart transplantation for FA dilated cardiomyopathy has been performed.

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Consultations

Goulipian and colleagues have mentioned the role of orthopedic shoes combined with physical therapy. Their results demonstrated that orthopedic shoes improved gait disorders in a patient with Friedreich ataxia. [20]

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Diet

No data exist to suggest that any alteration of diet would affect the onset, progression, or outcome of this disease.

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Activity

No data exist to suggest that any alteration of activity level would affect the onset, progression, or outcome of this disease.

In regards to the delivery and utilization of oxygen in response to exercise, near infrared muscle spectroscopy may be an effective tool for monitoring the biochemical and functional features of FA.

A study by Milne, et al. concluded that management of spasticity and reduced muscle length should be considered in people with FA at disease onset to optimize function. [55]

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