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Lorenzo's Oil

MooScience: calf with shadowLorenzo Odone was a boy with a rare and debilitating disorder, childhood onset X-linked adrenoleukodystrophy (ALD). This genetic disease strikes boys between the age of 4-8 and normally results in death several years later. Children with ALD have nervous system deterioration including deterioration of language and speech, loss of muscle control, hearing impairment, vision loss, cognitive impairment, seizures and eventually long term coma and death.

Lorenzo developed the symptoms of ALD at age four. He was a bright and curious child who spoke three languages. Suddenly he begin to slur his speech, lose his footing and throw tantrums at school. His concerned parents, Augusto and Michaela Odone, urgently sought help for their son. It was two long years before they were given a diagnoses, ALD. Not much was known about ALD in the early 1980's except that it was fatal and incurable. The doctors gave Lorenzo two years to live.

Lorenzo's loving father Augusto, was dismayed to find that ALD research was underfunded and neglected at the time. In addition, the scientists involved in researching ALD were widespread and most had never met face to face. Augusto Odone organized a ALD conference to bring together all the experts in the field. He also provided funding to try to find a cure for his son. Working together, Mr. Odone and a team of scientists developed Lorenzo's Oil. Although Lorenzo's Oil was not a cure and Lorenzo remained in a coma like state, the Odone family believed that it helped stabilize Lorenzo and extended his life. In spite of being blind, deaf and physically immobile Lorenzo was able to respond to family members by blinking or moving his fingers. Lorenzo died in 2008 at age 30; the average life expectancy of a child with ALD is 1-10 years after diagnosis.

One of Augusto's collaborators was Hugo Moser MD, an ALD researcher and prominent scientist. Determined to combat ALD, Dr. Moser worked tirelessly until his own death in 2007 to study the effects of Lorenzo's Oil and to develop a genetic marker for ALD. Dr. Moser, his wife Ann Broody Moser, and other scientists ultimately found a genetic marker for ALD that allows for genetic testing for ALD.


What is Lorenzo's Oil?

Lorenzo's oil is a 4:1 mixture of oleic acid and erucic acid. Both of these oils are omega-9 fatty acids. Lorenzo's oil is believed to inhibit the long-chain fatty acids that ALD sufferers cannot metabolise (Kemp et al. 2005), however there are conflicting reports about this. Regardless of mode of action, Lorenzo's Oil must be given from an early age to be effective. One long term study gave Lorenzo's Oil to boys who were thought to be susceptible to ALD. This reduced their chance of contracting the active form of the disease by about half (Moser et al. 2005, Moser et al. 2007). Sadly, it does not seem to improve existing ALD symptoms (Van Geel et al. 1999). For more on Lorenzo's Oil, how to obtain it and how it is used for ALD treatment see The Myelin Project.

The Hollywood version of the Odones' search for a cure was made into a movie "Lorenzo's Oil" in 1992 with Augusto and Michaela played by Nick Holte and Susan Sarandon.


More on ALD

ALD is a extremely devastating metabolic storage and peroxisome disorder where a defect in the ALDP enzyme causes a build up of very long chain fatty acids (VLCFA) in the bloodstream. As bloodstream concentration of VLCFA increase it disrupts the myelin sheaths around nerve cells. Myelin sheaths are necessary for fast transmission of nerve impulses. It also impairs adrenal gland functioning causing Addison's disease.

There are two main forms of the disease; a childhood cerebral form that affects boys (5-12 years) and an adult onset form, adrenomyeloneuropathy, that manifests in adult men (20-40 years). Both are an inherited recessive genetic disorder linked to the X chromosome. This means the disease is passed on through the mother's side. Since women carriers have one normal X chromosome, they normally do not show signs of the disease at all or show it later in life. About 20% of women carriers show neurological symptoms that tend to increase with age. Often these involve bladder or lower limb weakness and are mistaken for other disorders.

VLCFA are mainly produced by the body. Since VLCFAs are long, they cannot be oxidized by the mitochondria. Instead, they must be processed in the peroxisome, which is basically the cell's recycling center. The peroxisome breaks down unneeded cellular components. The person with ALD cannot break down VLCFAs due to a missing ALDP enzyme. Normally ALDP escorts unwanted VLCFAs into the cell's peroxisome. If the enzyme is not functional or missing it cannot move unwanted VLCFAs into the peroxisome to be degraded and the VLCFAs build up in the body.


What is the Harm in VLCFA Buildup?

Very long chain fatty acids are hydrophobic (water hating) lipids that tend to stick in cellular membranes (Ho et al. 1995) and disrupt normal membrane function. This is toxic to many cells including brain neurons, adrenocortical cells, myelin producing oligodendrocytes and astrocytes (Whitcomb et al. 1988, Hein et al. 2008). It causes cell death of brain microglia through aberrant signaling (Eichler et al. 2008), oxidative protein damage (Fourcade et al. 2008), depolarization of mitochondria through increasing inner membrane permeability (Hein et al. 2008), and disruption of internal cellular calcium concentrations (Hein et al. 2008).



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  • Fourcade S, López-Erauskin J, Galino J, Duval C, Naudi A, Jove M, Kemp S, Villarroya F, Ferrer I, Pamplona R, Portero-Otin M, Pujol A. Early oxidative damage underlying neurodegeneration in X-adrenoleukodystrophy. Hum Mol Genet. 2008;17:1762-73. Pubmed. doi: 10.1093/hmg/ddn085 (full text)
  • Hein S, Schönfeld P, Kahlert S, Reiser G. Toxic effects of X-linked adrenoleukodystrophy-associated, very long chain fatty acids on glial cells and neurons from rat hippocampus in culture. Hum Mol Genet. 2008;17:1750-61. Pubmed. doi: 10.1093/hmg/ddn066 (full paper)
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  • Van Geel BM, Assies J, Haverkort EB, Koelman JH, Verbeeten B Jr, Wanders RJ, Barth PG. Progression of abnormalities in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy despite treatment with "Lorenzo's oil. J Neurol Neurosurg Psychiatry. 1999;67:290–299. Pubmed. Full text.
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