Study About Safety and Efficacy of Coenzyme Q10 in Progressive Supranuclear Palsy

Background and Rationale:

• Progressive Supranuclear Palsy (PSP, Steele-Richardson-Olszewski Syndrome) is a sporadic neurodegenerative disorder resulting clinically in a Parkinson syndrome (i.e. akinetic-rigid movement disorder) with prominent postural instability, oculomotor deficits, and cognitive decline (for review: Albers and Augood, 2001; Burn and Lees, 2002). With an average annual incidence of 5.3 per 100000 and an age-adjusted prevalence of 6.4 per 100000, PSP is as common as motor-neuron disease (Burn and Lees, 2002). There is no symptomatic treatment, because PSP patients do not respond to any known therapy (Albers and Augood, 2001; Burn and Lees, 2002). The progression of PSP is rapid and the median survival after onset of symptoms is 5-10 years (Albers and Augood, 2001). Presently, there is no known effective symptomatic or neuroprotective therapy for PSP.

• Evidence suggests an impairment of mitochondrial energy metabolism in PSP (Albers and Beal, 2002):

• Reduced cerebral glucose and ATP metabolism have been shown in functional imaging studies in PSP patients (Forster et al., 1988; Martinelli et al., 2000).
• Cybrid cells harboring mitochondrial genes from PSP patients have decreased ATP-levels and complex I activity (Swerdlow et al., 2000; Albers et al., 2001; Chirichigno et al., 2002).
• A tropical PSP-like tauopathy has been linked clinically and experimentally to the consumption of the fruit and teas of leaves of the tropical plant annona muricata rich in lipophilic complex I inhibitors (Caparros-Lefebvre et al., 1999; 2001). These clinical observations suggest a role for mitochondrial dysfunction in the etiology of PSP.

3.Coenzyme Q10 (CoQ10) is the physiological electron recipient of complex I. Exogenous CoQ10 (1.) enhances the electron transport by complex I and (2.) powerfully scavenges free radicals. Thus, CoQ10 has been shown to reduce the toxicity of complex I inhibitors in vitro (Menke et al., 2003) and in vivo (Beal et al., 1998

Inclusion criteria

• Diagnosis of clinically probable PSP (Litvan et al., 1996).
• Early stage PSP [PSP staging system ≤ III (Golbe, 1997)].
• Capability and willingness to give written informed consent to participate in the study.

Exclusion criteria

• Age > 85 years.
• Parkinson syndromes other than PSP (e.g. idiopathic Parkinson's disease, multiple system atrophy, diffuse Lewy body disease, FTDP17, symptomatic parkinsonism)
• Dementia [Mini Mental State Examination (MMSE) ≤ 24]
• History of epilepsy, structural brain disease, brain surgery, or electroconvulsive therapy
• History of stroke related to the onset or progression of PSP symptoms
• Arterial hypertension (systolic >180 or diastolic >110mm Hg)
• Thyroid dysfunction requiring thyroxin supplementation (CoQ10 may change its metabolism)
• Presence of other serious illnesses
• Insufficient contraception in male and pre-menopausal female participants. Accepted means of contraception are hormonal contraception, intrauterine devices, vaginal rings, preservatives, and abstinence.
• Pregnancy or lactation period
• Participation in other drug studies within 60 days before baseline visit.
• Use of CoQ10 within 60 days before baseline visit
• Use of any antioxidants (e.g. vitamin E, C) within 60 days before baseline visit
• Use of any drugs modifying mitochondrial activity within 60 days before baseline visit
• Use of statins within 60 days before baseline visit (inhibit endogenous CoQ10 production)
• Use of drugs interfering with catecholamine metabolism (e.g. reserpine, amphetamines, or monaomine oxidase-A inhibitors, methylphenidate, cinnarizine) within 30 days before baseline visit.
• Use of Levodopa within 30 days before baseline visit (CoQ10 may change its metabolism).
• An unstable dosage of CNS-active drugs (e.g. anxiolytics, hypnotics, tranquillizer, and antidepressants) within 30 days before baseline visit or throughout the study.
• An unstable dosage of other antiparkinsonian drugs within 30 days before baseline visit or throughout the study.