Friedreich Ataxia Treatment & Management
- Author: Jasvinder Chawla, MD, MBA; Chief Editor: Selim R Benbadis, MD more...
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.
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.
The other therapies that have been used are as follows:
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. 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.
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 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 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. 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.  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. 
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.
Pandolfo et al have recently reviewed the utility of deferiprone with specific regard to its iron chelating properties and clinical benefits.
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. However, future studies are needed.
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.
In addition, heart transplantation for FA dilated cardiomyopathy has been performed.
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.
No data exist to suggest that any alteration of diet would affect the onset, progression, or outcome of this disease.
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.
Harding AE, Zilkha KJ. Pseudo-dominant' inheritance in Friedreich's ataxia. J Med Genet. 1981 Aug. 18(4):285-7. [Medline].
Parkinson MH, Boesch S, Nachbauer W, Mariotti C, Giunti P. Clinical features of Friedreich's ataxia: classical and atypical phenotypes. J Neurochem. 2013 Aug. 126 Suppl 1:103-17. [Medline].
Nieto A, Correia R, de Nóbrega E, Montón F, Hess S, Barroso J. Cognition in Friedreich Ataxia. Cerebellum. 2012 Feb 16. [Medline].
Noval S, Contreras I, Sanz-Gallego I, Manrique RK, Arpa J. Ophthalmic features of Friedreich ataxia. Eye (Lond). 2012 Feb. 26(2):315-20. [Medline]. [Full Text].
Stolle CA, Frackelton EC, McCallum J, Farmer JM, Tsou A, Wilson RB, et al. Novel, complex interruptions of the GAA repeat in small, expanded alleles of two affected siblings with late-onset Friedreich ataxia. Mov Disord. 2008 Jul 15. 23(9):1303-6. [Medline].
Dürr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C, et al. Clinical and genetic abnormalities in patients with Friedreich's ataxia. N Engl J Med. 1996 Oct 17. 335(16):1169-75. [Medline].
Marmolino D. Friedreich's ataxia: past, present and future. Brain Res Rev. 2011 Jun 24. 67(1-2):311-30. [Medline].
Synofzik M, Godau J, Lindig T, Schöls L, Berg D. Transcranial sonography reveals cerebellar, nigral, and forebrain abnormalities in Friedreich's ataxia. Neurodegener Dis. 2011. 8(6):470-5. [Medline].
Borchers S, Synofzik M, Kiely E, Himmelbach M. Routine clinical testing underestimates proprioceptive deficits in Friedreich's ataxia. Cerebellum. 2013 Dec. 12(6):916-22. [Medline].
Bürk K, Schulz SR, Schulz JB. Monitoring progression in Friedreich ataxia (FRDA): the use of clinical scales. J Neurochem. 2013 Aug. 126 Suppl 1:118-24. [Medline].
Kosutic J, Zamurovic D. High-dose beta-blocker hypertrophic cardiomyopathy therapy in a patient with Friedreich ataxia. Pediatr Cardiol. 2005 Sep-Oct. 26(5):727-30. [Medline].
Li K, Besse EK, Ha D, Kovtunovych G, Rouault TA. Iron-dependent regulation of frataxin expression: implications for treatment of Friedreich ataxia. Hum Mol Genet. 2008 Aug 1. 17(15):2265-73. [Medline].
Trouillas P, Serratrice G, Laplane D, Rascol A, Augustin P, Barroche G, et al. Levorotatory form of 5-hydroxytryptophan in Friedreich's ataxia. Results of a double-blind drug-placebo cooperative study. Arch Neurol. 1995 May. 52(5):456-60. [Medline].
Brandsema JF, Stephens D, Hartley J, Yoon G. Intermediate-dose idebenone and quality of life in Friedreich ataxia. Pediatr Neurol. 2010 May. 42(5):338-42. [Medline].
Parkinson MH, Schulz JB, Giunti P. Co-enzyme Q10 and idebenone use in Friedreich's ataxia. J Neurochem. 2013 Aug. 126 Suppl 1:125-41. [Medline].
Lynch DR, Perlman SL, Meier T. A Phase 3, Double-blind, Placebo-Controlled Trial of Idebenone in Friedreich Ataxia. Arch Neurol. 2010 Aug. 67(8):941-7. [Medline].
Tomassini B, Arcuri G, Fortuni S, Sandi C, Ezzatizadeh V, Casali C, et al. Interferon gamma upregulates frataxin and corrects the functional deficits in a Friedreich ataxia model. Hum Mol Genet. 2012 Mar 23. [Medline].
Pandolfo M, Hausmann L. Deferiprone for the treatment of Friedreich's ataxia. J Neurochem. 2013 Aug. 126 Suppl 1:142-6. [Medline].
Milbrandt TA, Kunes JR, Karol LA. Friedreich's ataxia and scoliosis: the experience at two institutions. J Pediatr Orthop. 2008 Mar. 28(2):234-8. [Medline].
Goulipian C, Bensoussan L, Viton JM, Milhe-De Bovis V, Ramon J, Delarque A. Orthopedic shoes improve gait in Friedreich's ataxia: a clinical and quantified case study. Eur J Phys Rehabil Med. 2008 Mar. 44(1):93-8. [Medline].
Tsou AY, Paulsen EK, Lagedrost SJ, Perlman SL, Mathews KD, Wilmot GR, et al. Mortality in Friedreich ataxia. J Neurol Sci. 2011 Aug 15. 307(1-2):46-9. [Medline].
Weidemann F, Rummey C, Bijnens B, Störk S, Jasaityte R, Dhooge J, et al. The Heart in Friedreich Ataxia: Definition of Cardiomyopathy, Disease Severity, and Correlation with Neurological Symptoms. Circulation. 2012 Feb 29. [Medline].
Wilson CL, Fahey MC, Corben LA, Collins VR, Churchyard AJ, Lamont PJ, et al. Quality of life in Friedreich ataxia: what clinical, social and demographic factors are important?. Eur J Neurol. 2007 Sep. 14(9):1040-7. [Medline].
Paulsen EK, Friedman LS, Myers LM, Lynch DR. Health-related quality of life in children with Friedreich ataxia. Pediatr Neurol. 2010 May. 42(5):335-7. [Medline].
Beltinger A, Riffel B, Stöhr M. Somatosensory evoked potentials following median and tibial nerve stimulation in patients with Friedreich's ataxia. Eur Arch Psychiatry Neurol Sci. 1987. 236(6):358-63. [Medline].
Chamberlain S, Koenig M, Richter A, Palau F, Pandolfo M. Molecular analysis of the Friedreich's ataxia locus. Adv Neurol. 1993. 61:193-204. [Medline].
Collins A. Clinical neurogenetics: friedreich ataxia. Neurol Clin. 2013 Nov. 31(4):1095-120. [Medline].
Currier RD. A treatment for ataxia [editorial]. Arch Neurol. 1995 May. 52(5):449. [Medline].
Delatycki MB, Williamson R, Forrest SM. Friedreich ataxia: an overview. J Med Genet. 2000 Jan. 37(1):1-8. [Medline].
Di Prospero NA, Baker A, Jeffries N, Fischbeck KH. Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial. Lancet Neurol. 2007 Oct. 6(10):878-86. [Medline].
Epstein E, Farmer JM, Tsou A, Perlman S, Subramony SH, Gomez CM, et al. Health related quality of life measures in Friedreich Ataxia. J Neurol Sci. 2008 Sep 15. 272(1-2):123-8. [Medline].
Forrest SM, Knight M, Delatycki MB, et al. The correlation of clinical phenotype in Friedreich ataxia with the site of point mutations in the FRDA gene. Neurogenetics. 1998 Aug. 1(4):253-7. [Medline].
Friedman JH. Machado-Joseph disease/spinocerebellar ataxia 3 responsive to buspirone. Mov Disord. 1997 Jul. 12(4):613-4. [Medline].
Friedman LS, Farmer JM, Perlman S, Wilmot G, Gomez CM, Bushara KO, et al. Measuring the rate of progression in Friedreich ataxia: implications for clinical trial design. Mov Disord. 2010 Mar 15. 25(4):426-32. [Medline].
Hart PE, Lodi R, Rajagopalan B. Antioxidant treatment of patients with Friedreich ataxia: four-year follow-up. Arch Neurol. 2005 Apr. 62(4):621-6. [Medline].
Jitpimolmard S, Small J, King RH, Geddes J, Misra P, McLaughlin J, et al. The sensory neuropathy of Friedreich's ataxia: an autopsy study of a case with prolonged survival. Acta Neuropathol. 1993. 86(1):29-35. [Medline].
Johnson WG. Friedreich ataxia. Clin Neurosci. 1995. 3(1):33-8. [Medline].
Koeppen AH. The hereditary ataxias. J Neuropathol Exp Neurol. 1998 Jun. 57(6):531-43. [Medline].
Lane DJ, Richardson DR. Frataxin, a molecule of mystery: trading stability for function in its iron-binding site. Biochem J. 2010 Feb 9. 426(2):e1-3. [Medline].
Lynch DR, Lech G, Farmer JM, Balcer LJ, Bank W, Chance B, et al. Near infrared muscle spectroscopy in patients with Friedreich's ataxia. Muscle Nerve. 2002 May. 25(5):664-73. [Medline].
Mello KA, Abbott BP. Effect of sulfamethoxazole and trimethoprim on neurologic dysfunction in a patient with Joseph's disease. Arch Neurol. 1988 Feb. 45(2):210-3. [Medline].
Pandolfo M. Friedreich ataxia. Handb Clin Neurol. 2012. 103:275-94. [Medline].
Pandolfo M. Friedreich's ataxia: new development and perspectives. Generations: The Official Publication of the National Ataxia Foundation. 1999. 27(1):6-9.
Schipper HM. Neurodegeneration with brain iron accumulation - clinical syndromes and neuroimaging. Biochim Biophys Acta. 2012 Mar. 1822(3):350-60. [Medline].
Schmucker S, Puccio H. Understanding the molecular mechanisms of Friedreich Ataxia to develop therapeutic approaches. Hum Mol Genet. 2010 Apr 22. [Medline].
Schulz JB, Pandolfo M. 150 years of Friedreich ataxia: from its discovery to therapy. J Neurochem. 2013 Aug. 126 Suppl 1:1-3. [Medline].
Sedlak TL, Chandavimol M, Straatman L. Cardiac transplantation: a temporary solution for Friedreich's ataxia-induced dilated cardiomyopathy. J Heart Lung Transplant. 2004 Nov. 23(11):1304-6. [Medline].
Stockner H, Sojer M, Hering S, Nachbauer W, Seppi K, Schmidauer C, et al. Substantia nigra hypoechogenicity in Friedreich ataxia. Mov Disord. 2012 Feb. 27(2):332-3. [Medline].
Subramony SH, McDaniel O, Vedanarayanan VV. Very late-onset Friedreich's ataxia. Mov Disord. 1999. 14(5):904.
Trouillas P, Takayanagi T, Hallett M. International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology. J Neurol Sci. 1997 Feb 12. 145(2):205-11. [Medline].
Voncken M, Ioannou P, Delatycki MB. Friedreich ataxia-update on pathogenesis and possible therapies. Neurogenetics. 2004 Feb. 5(1):1-8. [Medline].
Wills AJ, Marsden CD. Fifty Neurologic Cases from the National Hospital. 1999.
Zouari M, Feki M, Ben Hamida C, Larnaout A, Turki I, Belal S, et al. Electrophysiology and nerve biopsy: comparative study in Friedreich's ataxia and Friedreich's ataxia phenotype with vitamin E deficiency. Neuromuscul Disord. 1998 Aug. 8(6):416-25. [Medline].
Elincx-Benizri S, Glik A, Merkel D, Arad M, Freimark D, Kozlova E, et al. Clinical Experience With Deferiprone Treatment for Friedreich Ataxia. J Child Neurol. 2016 Mar 29. [Medline].
Milne SC, Corben LA, Yiu E, Delatycki MB, Georgiou-Karistianis N. Gastrocnemius and soleus spasticity and muscle length in Friedreich's ataxia. J Clin Neurosci. 2016 Mar 25. [Medline].
Aranca TV, Jones TM, Shaw JD, Staffetti JS, Ashizawa T, Kuo SH, et al. Emerging therapies in Friedreich's ataxia. Neurodegener Dis Manag. 2016 Feb. 6 (1):49-65. [Medline].
Rezende TJ, Silva CB, Yassuda CL, Campos BM, D'Abreu A, Cendes F, et al. Longitudinal magnetic resonance imaging study shows progressive pyramidal and callosal damage in Friedreich's ataxia. Mov Disord. 2016 Jan. 31 (1):70-8. [Medline].