Alpha-lipoic Acid/L-acetyl Carnitine for Progressive Supranuclear Palsy
Condition: Progressive Supranuclear Palsy
MeSH terms: Paralysis; Supranuclear Palsy, Progressive
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Studies have shown that alpha-lipoic acid and L-acetyl carnitine may have some
      neuroprotective activities and it is hoped that they could be helpful for people with
      neurodegenerative illnesses such as progressive supranuclear palsy (PSP).

      The purpose of this study is to find out whether the nutritional supplement alpha-lipoic
      acid/L-acetyl carnitine is safe and well-tolerated in individuals with PSP when given daily,
      and whether it affects their well-being, brain scan measurements and blood tests that measure
      the energy metabolism in cells.
    

Detailed description: 
      Multiple lines of evidence support mitochondrial dysfunction and oxidative stress playing a
      role in the pathogenesis of atypical Parkinsonism, including PSP. Such dysfunction may well
      contribute to the tau pathology that is well-recognized in PSP, thus providing a link between
      the two processes. This pathway therefore represents an excellent potential target for novel
      therapeutic intervention in neurodegenerative disorders, and a number of well-tolerated and
      safe nutritional supplements have been identified that appear to augment mitochondrial
      function, and improve oxidative stress.

      Alpha-lipoic acid and L-acetyl carnitine are two nutritional supplements that have received
      increasing attention as potential neuroprotective interventions in neurodegenerative and
      other disease states. Alpha-lipoic acid/L-acetyl carnitine had been demonstrated to improve
      learning in aged beagles over 2 months of administration, and showed a trend to improve
      cognitive function in a mouse model of Alzheimer's disease (human apoE4 transgene). Moreover,
      alpha-lipoic acid/L-acetyl carnitine was neuroprotective in a mouse model of Parkinson's
      disease (rotenone-induced parkinsonism), with effects including decreased oxidative stress,
      and increased mitochondrial biogenesis. In fibroblasts derived from individuals with
      Alzheimer's disease, alpha-lipoic acid/L-acetyl carnitine reduced increased levels of
      oxidative stress. In healthy men exposed to intensive exercise, alpha-lipoic acid provided
      antioxidant effects systemically (decreased peroxidation). L-acetyl carnitine improved
      neuroimaging correlates of cerebral blood flow in 30 subjects with dementia. These
      nutritional supplements have been safe and well-tolerated, and they have been tested in age
      groups including children, up to the elderly. Alpha-lipoic acid had been successfully
      administered over an extended period in an open-label trial in Alzheimer's disease.
      Importantly, it appeared that the effects of alpha-lipoic acid and L-acetyl carnitine when
      administered together were significantly augmented (100-1000 times), as opposed to when
      administered separately. This therefore provided a strong rationale to test the two in
      combination.

      In addition to monitoring clinical features, we had also chosen to test physiologic effects
      of alpha-lipoic acid/L-acetyl carnitine in our PSP subjects using two biomarkers that provide
      measures of mitochondrial function and oxidative stress. This was particularly important,
      since both supplements may act by multiple mechanisms. 1H MRSI is a technique that provides
      insight into the metabolism of several endogenous brain compounds, most notably
      N-acetyl-L-aspartate (NAA), choline-containing compounds (Cho), and creatine and
      phosphocreatine (Cr). A number of studies of mitochondrial function had firmly established
      the utility of 1H MRSI in probing potential mitochondrial energy metabolism dysfunction. 31P
      MRSI provided complementary information to probe in vivo mitochondrial energy metabolism and
      tissue energetics. In addition, we proposed using markers of oxidative damage (including
      8-hydroxydeoxyguanosine) as well as metabolomic analysis to test a composite panel of
      quantitative measures in plasma. We used an established metabolomic platform that has proven
      to identify specific combinations of metabolites differing between neurodegenerative disease
      states (including Parkinson's disease, Huntington's disease) and healthy controls. Our
      overall aim was to generate an "oxidative biomarker" and "metabolomic read-out" of the
      peripheral biochemical effects of alpha-lipoic acid/L-acetyl carnitine in PSP.
    

Intervention name(s): alpha-lipoic acid and L-acetyl carnitine
Intervention type(s): Drug
Intervention description(s): alpha-lipoic acid and L-acetyl carnitine capsules, 600mg/1.5g daily for 6 months
Other intervention name(s): Juvenon
Intervention MeSH terms: Thioctic Acid; Acetylcarnitine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Progressive supranuclear palsy; alpha-lipoic acid; L-acetyl carnitine; antioxidant; magnetic resonance spectroscopy; neurodegeneration; glutathione