Monday, 23 September 2013

Huntington's Disease

Huntington's disease (HD) is a rare, hereditary, fatal (death usually occurs 10-25 years after the first symptoms appear) neurodegenerative disorder (i.e. a neurological [pertaining to the brain, spinal cord and/or nerve cells] yet progressive disorder) that can strike persons at any time in life. It causes a progressive decline in motor function (your ability to control your normally, voluntary movements), cognitive function (memory, learning, etc.), emotional stability, connection with reality (in the later stages people with the disorder can become psychotic with many of the classic symptoms of paranoid schizophrenia) and various other neurological functions. The first symptom is usually chorea (an abnormal involuntary movement disorder that often presents with involuntary flailing movements) hence the previous name of the condition, Huntington's chorea.1

It is due to the build-up of a faulty (or mutated) huntingtin protein (mHtt) which is due to a mutation in the huntingtin gene (HTT). This gene is used to create the huntingtin protein which plays a key role in various cellular processes in the brain and testes. The gene is inherited in an autosomal dominant fashion (i.e. it is inherited in a manner that is totally independent of the sex of the parent and the child. This is because we all get two autosomes [the type of chromosome on which the huntingtin gene is found; these are the non-sex chromosomes] of each variety [there's 21 different autosomes], one from our father, one from our mother. It takes just one autosome that contains a faulty huntingtin gene to cause Huntington's disease). The faulty huntingtin protein builds up and this leads to neuronal (electrically-signalling brain, spinal cord and nerve cell [in this case mostly just brain cell]) dysfunction and death (although we're not sure exactly how).1

At this point in time there are limited treatment options for people with Huntington's disease. Most treatments are aimed at making the patient as comfortable as possible as they die. Treatments that are designed to do this include neuroleptics (antidopaminergic drugs; drugs that counteract the actions of the neurotransmitter, dopamine, throughout the nervous system [brain, spinal cord and nerves] particularly in the basal ganglia -- the part of the brain that takes the biggest hit in Huntington's disease. It plays a key role in controlling our voluntary movements. Neuroleptics are basically the older antipsychotic medications [the so called "typical" antipsychotics] and some of the older antiemetics [anti-nausea and vomiting]), benzodiazepines (e.g. diazepam [VALIUM], clonazepam [RIVOTRIL]), dopamine-depleting agents (e.g. reserpine, tetrabenazine) and valproate (EPILIM, DEPAKENE, DEPAKOTE) which are designed to help with the choreas typical of HD. Likewise if symptoms include muscle rigidity and slowed movements then dopamine agonists (receptor activators; compounds that mimic dopamine's effects in the body) or levodopa (a compound the body uses to synthesise dopamine) are preferred. Depression is also common in patients with HD and is often treated standard antidepressants such as sertraline (ZOLOFT), fluoxetine (PROZAC), etc. None of these treatments are believed to be disease-modifying i.e. treatments that actually slow (or "modify") the course of the disease.1

I theorise that valproate may have disease-modifying effects in HD seeing how it is a known histone deacetylase (HDAC) inhibitor (which alter the generation of proteins from genes) and HDAC inhibitors are known to slow the progression of HD in animal models of the disease.2

Coenzyme Q10 is an enzyme that participates in the electron-transport chain that provides a significant portion of a cell's energy. Consequently it plays a pivotal role in mitochondrial (the "power house" of cells) function. When it's supplemented with dietary supplements it provides antioxidant, anti-inflammatory and neuroprotectant (neuron-protecting) effects. In animal models of HD it was found to possess diseases-modifying effects.3

Creatine, another naturally-occurring antioxidant, has been found to possess protective effects in animal models of HD.3,4

Reference List:

  1. Revilla FJ. Huntington Disease. 2013 May 14 [cited 2013 Sep 23]; Available from:
  2. Sadri-Vakili G, Cha J-H. Histone Deacetylase Inhibitors: A Novel Therapeutic Approach to Huntingtons Disease (Complex Mechanism of Neuronal Death). Current Alzheimer Research [Internet]. 2006 Sep 1 [cited 2013 Sep 23];3(4):403–8. Available from:
  3. Yang L, Calingasan NY, Wille EJ, Cormier K, Smith K, Ferrante RJ, et al. Combination therapy with Coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson’s and Huntington’s Diseases. Journal of Neurochemistry [Internet]. 2009 [cited 2013 Sep 23];109(5):1427–39. Available from:
  4. Dedeoglu A, Kubilus JK, Yang L, Ferrante KL, Hersch SM, Beal MF, et al. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington’s disease transgenic mice. J Neurochem. 2003 Jun;85(6):1359–67. 

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