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ALD and LORENZO’S OIL-Howmuchdo you know?| By:N. BAFAZINI;Student #:2009078425
BOC344
TURNING MYSTERYINTO VICTORY;MAKING A MARKINTHE MEDICAL HISTORY;
LEAVING NO ROOM FOR ERROR.-

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INTRODUCTION:
To introduce this study on a very rare genetic disorder disease known as
Adrenoleukodystrophy (ALD), I would first like to refer to the movie
Lorenzo’s Oil. This movie gives a clear perspective and understanding of the
journey people afflicted by ALD goes through, the sufferings, the impacts on
family, on societies etc. and how it all changes and all they ever had fades
into nothing.
In this movie, Lorenzo is portrayed first as a normal boy with a normal
childhood; doing everything a child of his age did until it all changed in a
split second. He moved from hero to zero. First he showed signs of aggression
towards other students which bothered teachers. They explained this radical
behavior as hyper activeness and disorientation. However, the parents-Augusto
(father) and Michaela (mother)-could not understand all that as they had
never seen him so, until they did. Taking him to a doctor, that is where
after a number of tests which ruled out a lot of diseases, it was discovered
that he has ALD. As the severity of the disease and how long its victims get
to live-two years at most- was explained to them, they refused to accept such
a “curse” rather, however devastated and torn they were; they devoted their
time, lives, energy and all to standing up and fighting back. They took it
upon themselves to find a way to “beat” the disease proclaimed as a dead -end
type of ailment with no cure nor hope.
It is every one’s fear to watch our loved ones suffer to death knowing that
there’s nothing we can do to help. Even when given zero chances and no how
much of a hopeless situation we seem to be swamped in, we all do try a ll we
can so that at the end of the day we can at least be able to say,” I tried, I
did what I could, when I could up to the limit of my knowledge and when I
knew better I did better, therefore if I knew best, I could have done more;
either way, I tried!” I know this very well because I know it from first
hand. Last year March; those were my words at the end of it all. Even though
I still lost her-my little sister-only at the age of nine after going through
hell in hope that she would make it, I still know even today that I did all I
could, even overstepped my rank, but.... However, Lorenzo’s parents did all
the research and regardless of their lack of neither biological nor medical
health knowledge, they did, with their unstoppable determination and devotion
find a way to help all the children with ALD by manipulating the biochemical
pathway of the disease. This proves that it’s not always about how much one
knows, but about how bad they want something and how far they are willing t o
go, that their hard work will pay back.
At the end, Lorenzo’s oil is developed of which as a result of it, Lorenzo
started showing signs of improvement such as ways of communication, which
meant that his levels of VLCSFAs were back to normal. At this moment, it
certainly did not matter how many friends and/or family they lost, how much
rejection they encountered, how much criticism on their lack of knowledge was
thrown at them in the process, finally; they conquered and their son would
see more years-which he did give that his mother even died before him, who
would have guessed??

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EPISODE 1
SHORT HISTORY...
A great interest in the disease has was just recently, maybe due to what a
medical breakthrough Lorenzo became, but it has been around for quite long.
Moser et. al (1997), the disease was first seen in 1910 by Haberfeld and
Spieler in a boy who lost whole body function at the age of six and died
around the age of 8. At that time, the biochemical pathways leading to the
disease were not know even though it was obvious that the myelin was been
degraded in children cerebral hemisphere, which was discovered 3 years later.
It presented itself as multiple sclerosis and so for some time it was treated
as one of those yet with distinct differences, until then and it was grouped
under X-linked genetic disorder. Finally the symptom of the disease was
discovered in 1953 by Powers and Schaumburg. With some advancement in
technology then, they were able to realize cholesterol deposit in the brain
which prompted a conclusion that it is lipid/fatty acid based especially very
long chains of saturated fatty acids. Then followed the finding of the
location at which the reactions occur as well as enzyme(s) responsible. Then
finding that it’s an oxidative reaction that’s at fault, it dragged along the
fact that fatty acid beta-oxidation occurs in the peroxisome (Sigh et al
1984a, b). mostly with inhibitory disorders, if the first step in the
reaction is inhibited due default enzyme, then the rest of the steps do not
happen and so this was the believe; that fatty acyl coA synthase is the
inactive enzyme until it was discovered that the faulty gene actually codes
for a membrane associated transporter protein called ALD-Protein, which
facilitates their transportation across the membrane to the peroxisome for
their beta-oxidation. The saturated very long chains of fatty acids (VLCSFA)
accumulation were then treated through assign a dietary protocol of combined
mono unsaturated fatty acids, oleic (4): erucic (1) acids which are a form of
enzyme biochemical pathway manipulation strategy. However, some therapeutic
strategies such as bone marrow transplants and Immunosuppressions were
brought into use and bone marrow transplantation seemed better... regardless,
the breakthrough of the disease was the development of Lorenzo’s oil...
EPISODE 2
.....BUT REALLY, WHAT IS ALD?
The acronym ALD stands for Adrenoleukodystrophy; a genetically inherited
disorder resulting from the degradation of the lipid myelin sheath
surrounding the neurons; which intern is caused by the over accumulation of
Long Chain of Saturated Fatty Acids in the brain. This brings up and
important question though, what is MYELIN?
Myelin is produced by plasma cell of Schwann cells and is highly composed of
a type of sphingolipids called sphingomyelin. This sheath is in actual fact a
mound of membrane layers surrounding the cells of the central and peripheral
nervous system-(neurons). Its function is to insulate-has high lipid content
than of protein-, protect as well as prevent conduction across the membrane.

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Within this type of lipid, (sphingolipids); there is a continuing metabolic
turnover in both synthesis and degradation. The latter occurs in lysozomes
through the action of hydrolytic enzymes. These pathways however, appear to
be massively connect to “congenital” diseases named lipid storage diseases,
(sphingolipodoses), i.e. highly severe diseases associated with incompetence
and/or deficiency in any of the degradative enzymes leading to an
accumulation of the substrate. This therefore imposes severe malfunctioning
of the central nervous system as they-sphingolipids- are in large amounts in
nervous tissue. The efficiency in neural impulse transmission, i.e.
movements, thinking, speech, etc. all depends on the amount of insulation
around them by the myelin hence why upon its degradation; serious symptoms
are observed on those inflicted such as ALD.
There is however different forms of the disorder. There is
Adrenomyeloneropathy (AMN). It presents itself as multiple sclerosis-meaning
there is gradual but progressive loss of body function yet there is no great
damage to the brain. It has the occurrence percentage of 40%-45% and affects
males of middle age. It can in some people appear as Addison’s disease and/or
adrenal gland disorder as a start. This is mainly due to its mechanisms of
attack,-damages the adrenal gland-and any children of 2 year and above
diagnosed with Addison’s have to be tested for ALD. The most adverse of them
all is the type that destroys the nervous system, the entire body’s control
center; childhood cerebral type administering progressive deterioration of
the myelin in the cerebral cortex, spinal cord, white matter and brain
inflammation. The first diagnosis can be made at the ages of four to eight
with immediate disability, loss of cognition and shut down, finally death
mostly even before the first decade; and this is of course the type Lorenzo
had.
EPISODE 3
THE GENETICS BEHIND ALD- IT’S ACTUAL CAUSE...
ALD is an autosomal recessive X-linked genetic disorder affecting males only.
What does this mean and why is that??
For every phenotype, there is a gene that codes for it which intern is coded
for by a pair of alleles. The genetic makeup of an individual is such that in
each pair, one is maternal while the other is paternal. Within them, there
are recessive and dominant forms where the latter actually fully overrides
the expression of the former when both in an individual. That is for example,
if in a flower red color is encoded by a dominant allele and white by a
recessive one, then the flower color is going to be red if they both co-
exist. However, it is not just this simple, genetics deals with
probabilities. There is three ways in which the genetic makeup can be
acquired, homozygous dominant (AA), homozygous recessive (aa) or heterozygous
(Aa). When speaking in X-linked/ sex linked genetics terms, there is also
hemizygosity- dominant and recessive- which refers to males as they only have

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one X chromosome-see sex determination- they receive maternally and then the
sex determining Y chromosome (XAY or XaY) while females have both Xes (XAXA,
XaXa or XAXa). This therefore means that in X-linked disorders, males will
always be inflicted if the mother is inflicted, again it’s a probability.
SEX DETERMINATION:
NB: XX=FEMALE ANF XY=MALE
With ALD, the disorder coding allele is recessive meaning the son will only
be inflicted if by chance he receives the recessive allele other than the
dominant one,(unfortunate lottery, so they call it.) giving him XaY genotype.
However, the mother in this case shows no signs or symptoms of the disorder
yet the son receives the disease from her, how is that? Well, since its
recessive, the mother has the dominant allele that tramps the expression of
the recessive one and is
therefore just a carrier of the
disorder but not affected while
sons carry a 50% chance of
having the disorder and girls a
50% chance of being carriers. -
X-LINKED RECESSIVE:
GENOTYPES:
Mom=XAXa
Dad=XAY
Results: Sons: 50% Unaffected
50% affected.
Daughters: 50% unaffected
50% carrier
As explained in GEN 216,
pedigrees.

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There is a very slight chance though; of having affected female give how rare
the disease is (1 in 100,000 occurrence frequency. allelic frequencies) and
its motility rate. If Lorenzo per say, married a carrier wife:
GENOTYPES:
Lorenzo= XaY
Wife= XAXa
XA Xa
Xa XAXa XaXa
Y XAY XaY
RSULTS: OUT OF ½ GILS AND ½ BOYS
½ AFFECTED AND ½ UNAFFECTED in both sexes but the female is a carrier.
With non-sex linked inheritance such as mitochondrial either dominant or
recessive but in this case focusing on the recessive form, the faulty gene/
allele need not to be carried specifically on the X chromosome- (see ALD
chromosome mapping- mapped as Xq28, terminal segment of the X chromosome arm
(Moser et. Al 1981). For example:
PARENTAL GENOTYPES: Parent 1= AA (homozygous dominant)
Parent 2= Aa (heterozygous)
PUNETTE SQUARE:
A A
A AA AA
a Aa Aa
RESULTS: ALL UNAFFECTED; 50% homozygous dorminant And 50% heterozygous/
carriers

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A a
A AA Aa
a Aa aa
RESULTS: ¾ UNAFFECTED with 2/4=carriers and ¼ homozygous dominant. In this
case, there are ¼ chances of having an affected child even though it cannot
said for certain whether its boys or girl. This means both parents have to be
carriers of the diseases and are not affected.
X-ALD CHROMOSOME MAP:
ALLELIC FREQUENCIES CULCULATIONS: - just for interest sake:
Calculations are done using the Hardy-Weinberg law equation. This law works
under a number of assumptions such as no change in gene frequency from
generation to generation, no mutation, migration, genetic drift, inbreeding
and selection, large population with random mating. ALD (ignoring that it’s
X-linked) has an incidence of 1/100,000= 0.00001 (aa) hence the frequency of
individuals with it in a population is represented by q2; its recessive.
Equation: p2 + 2pq + q2 =1
Frequency of recessive gene:
q= √q2= √0.00001 = 0.00316 (a)
p + q = 1; therefore p frequency = 1-q
= 1-0.00316 = 0.997 (A)
P2 = (AA) = (0.997)2 = o.994.
Frequency of carriers (Aa): 2pq = 2(0.997) (0.00316) =0.00631.
All should add up to 1; (0.997)2 + 2(0.997*0.00316) + (0.00316)2= 1

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NB: IN X-LINKED DISORDERS: X-linked gene in question will equal the frequency
of males (XY) expressing the X-linked trait. For females (XX), the frequency
of having the gene will be = q2 if only the gene frequency = q.
EPISODE 4
.......ANY SYMPTOMS AND CAUSE
As it is with every disease, there are of course symptoms ALD imposes.
However, let me speak in particular about those Lorenzo showed. He first
showed aggression, hyperactivity and disorientation which were followed by
severe symptoms such as loss of vision, hearing, movement, difficulty in
swallowing, fatigue, loss of coordination and more. The progression is due to
the inability of the body to re-build its myelin like it can with dead tissue
leading to increased destruction of the sheath with time. With each form of
the disorder, there is symptoms associated and the rate of progression differ
greatly in accordance to onset age, length of survival and neuropathology and
so the rate of progression is slower in AMN. However, the prime biochemical
basis of the disease remains unvarying; i.e. the increased levels of un-
branched saturated VLCFAs.
All the symptoms mentioned above are a visual projection of internal
biochemical reaction causing the disease.
Mostly, genetic disorders are associated with enzyme malfunction due to a
faulty gene that codes for it. For instance, if the mutated enzyme is
catabolic and catalyzes glucose metabolism, there will be glucose build up in
the body, no glycolysis, hence no intermediates for Krebs cycle or any other
metabolic pathways which are necessary for cellular functions and survival as
they yield energy to facilitate all that. This will consequently result in a
number of severe problems.
Nonetheless, default in transporter proteins that facilitate substrate or
enzyme transportation across the membrane to their precise location of
catalysis, can also pose similar inconveniences. In the case of ALD, the
patient has an impaired ability to metabolize saturated VLCFA, resulting in
their excessive accumulation; in particular tetracosanoic acid (lignoceric,
C24:0) and Hexacosanoate (cerotic C26:0). It was discovered that it is not
about the enzyme responsible for their catabolism rather the ALD-Protein, a
form of ATP- Binding cassette, responsible for their transportation to the
peroxisome where they are broken down through beta-oxidation; (or peripheral
tissue or mitochondrial matrix for short fatty acids). This process provides
the cell with a lot of intermediate giving it of energy (ATP) essential for
all cellular reactions.- (it yield acyl coA, FADH2, NADH and CO2 + H2O-all
release a lot of energy upon oxidation.-see reaction 1.)
Before the gene was isolated by positional cloning (Moser et. al. 1993); it
was assumed that the problem was failure in fatty acyl- coA synthase
activation thereby unable to carry out the very first step in fatty acid
beta-oxidation- cycles of dehydrogenation, hydration, dehydrogenation and
thiolytic cleavage-; consequently putting at halt all reactions that follow

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thereof. However, it was discovered that in animals, the peroxisomal
oxidation only goes up to C4 and C6-acyl-coA which are not very to transport
throughout the body or even to excrete along with urine. The products are
thereby transported to the mitochondria-now that they are shorter- where
further oxidation is bound to occur.
Reaction 1 :( Matthews, Van Holde, Ahern, Biochemistry 3rd Edition, page 646)
E + FAD + R-CH2-CH2-C=0-S-CoA R-CH=CH-C=O-S-CoA +E-FADH2
E-FADH2 + O2 E-FADH + H2O2
H202 H2O + 1/2O2
ENERGY YEILD FROM OXIDATION:
Acyl-CoA 12 ATPs
FADH2 2 ATPs
NADH2 3 ATPs
NB: this is per mole of a cofactor.
EPISODE 4
WHAT ARE FATTY ACIDS??
These are amphipathic molecules made of a fatty-acyl group and a hydrocarbon
chain. They consist of a polar (hydrophilic) carboxylic head group and a non-
polar (hydrophobic) hydrocarbon chain tail, project different structures,
degree of unsaturation, length and more. There are two main forms though,
saturated and unsaturated and in both, they are either long-(>24 carbons) or
short (1, 16 or 18 carbons). Their relationship with water is the fundamental
bases of membranes structure- the hydrophobic tails are converge towards one
another inward while the hydrophilic heads get in contact with water.
Health wise, the unsaturated form is preferred over unsaturated. This is
mainly due to the fact that the double bonds form bents within the molecule
hence are easily broken down and the more the double bonds the less the
energy (temperature) required to degrade them; especially the cis double bond
since trans bond tend to mimic the saturated fatty acid make-up therefore
still not good. However most fatty acids synthesized by the body have cis
double bonds and are unsaturated, e.g. oleic acid (see fig1). Saturated fatty
acids in one hand, they form a very tightly packed and rigid structure,
therefore the more saturated and longer the chain, the more the energy the
body expends to break them down -10,000 times slower deterioration (Ito et.al
1995) see fig.2.However, unsaturated fatty acids can be converted to
saturated fatty acids through addition of Hydrogen- hydrogenation- thereby
breaking the double bond; e.g., vegetable oil to margarine.
CATALASE

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Figure 1 Oleic acid Figure 2 Cerotic acid
With ALD, be in context; C24 and C26 are the saturated very long chains of
fatty acid that seem to be of very high levels in the blood, in nervous
tissue, adrenal cortex etc. Even though Lorenzo was placed on a certain diet
that restricted his consumption of foods that contained VLCFAs meat, fish,
cheese, peanut butter etc., his levels kept increasing, as the body continues
their biosynthesis. These are the two ways in which the body acquires them.
EFFECTS OF THEIR EXCESSIVE ACCUMULATION –VLCFA- IN THE BODY/BRAIN...
Fatty acids are efficient in energy storage, heat production and insulation
due to the carbon in the head group being fully reduced leading to production
of a lot of energy upon its oxidation. The myelin sheath is in actual fact
responsible for neuron insulation. In a person with ALD cells with normal
cDNA, there is a smooth distribution of VLCFAs within respective tissues and
the opposite is true for ALD. Their continued accumulation, especially in the
brain; results in their coiling around the myelin sheath and degrading
it.(fig.3) The mechanism in which this happens is not very clear though, but
speculation is based on their structure. The fact that they have no kinks
prompts their ability to associate themselves with the myelin, making it
soluble and liquefying it leading to its wash away from the neurons. It does
this by surrounding the myelin with the hydrocarbon head with the hydrophilic
heads sticking out- forming some kind of a micelle around it.
Figure 3 .DESTROYED NYELINE SHEATH AROUND NEURONS; & HEALTHY MYELIN

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EPISODE 5
DIAGNOSIS AND TREATMENT
DIAGNOSIS:
ALD patients show very high levels of VLCSFAs in their bodies to an a point
where they are reflected in body fluids and this aids the diagnosis using
blood plasma and skin fibroblasts (Moser et. al 1983a). Culturing of the
tissues/cell and checking their level of VLCSFA can therefore give doctors a
definite answer of whether the person has the disorder and even the level the
disease severity given the levels. There is however, a room for error, i.e.
there can be found false negatives, as a result other advanced techniques
such as biochemical methods and gene mutational analysis of the ALD -Protein;
are employed especially for the diagnosis of less adverse forms of ALD like
AMN in grown-ups and women heterozygous for the disease. Brain scans-MRIs- of
patients will also display abnormalities on the region of white matter. ( See
fig.5)
Figure 5 BRAIN SCANS SHOWING DETORIORATION IN MYELIN
TREATMENT AND CURE:
There is no cure for the disorder, unfortunately but there are proposed forms
of treatment. To design treatment for any disease, its mechanisms of attack,
biochemical pathways as well as its causes have to be investigated and
manipulated. This is exactly what the “Odones” did. Augusto tried to find the
easier and everyday life experience way of explaining the problem so as to
find the treatment and that was when he came up with “the kitchen sink
model.” PLEASE REFER TO THE HARD COPY; SAME PAGE!
In the model, the sink is representative of the blood, the two taps, one for
VLCSFAs acquired form food and the other for those acquired though natural
biosynthesis. The opening to the drain represents excretory or degradative
ways while water represents the VLCSFAs. Logically, as both taps are open
with the drain opening closed, the water fill up the sink until the opening
is opened and as a certain volume of water comes in, a certain volume is
released to avoid overflow. However if just one tap is open, the volume of
water coming definitely goes down and so is one that released. With ALD, it
did not seem to be the case in Lorenzo’s blood. Even though the fatty acids

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from foods were eliminated, there seemed to be no difference, the levels
remained high, and this was a paradox he had to understand how it was
happening as it helped him realize that the problem is in their biosynthesis.
It took him a lot of research but he finally found the source of the problem.
He formulated yet another model in which two different types of paper clips
were used. One kind represented the VLCSFA-“bad guys” and the other
unsaturated long chain fatty acids-“good guys”. One clip represents two
carbons and Deirdre and him the enzymes each facilitating its own reaction.
Assuming that the enzymes add the carbon in more or less the same rate in
either form when elongating fatty acid during their biosynthesis, what could
cause the good guys decrease as the good guys increase? This stipulated that
there has to be so kind of a relationship between the two enzymes because
that would be the only explanation to the product of one inhibiting another.
This is the “paper clip model” To his surprise; the answer to this paradox
came to him in a form of a dream.
Up to here; he realized that the whole process is enzyme controlled but could
not yet tell how many enzymes were involved. In his dream, both chains of
paper clips were moving at the same time but they were both pulled by one
person; Lorenzo. In this scene, Lorenzo as well represents an enzyme and he
pulling both chains alone implicated that there is only one enzyme
responsible for the biosynthesis of both forms of fatty acids and this was
the solution to both paradoxes.
Enzyme activity is a very complex mechanism but it can be manipulated if
understood. In ALD, looking at the paradoxes, the biosynthesis is at equal
rate but the degradation rates differ, the VLCSFAs are not metabolized at all
hence only they accumulate. This brought up
the competitive inhibition mechanism of
enzyme activity. In the mechanism, the
principle is the substrate of higher
concentrations will be of preferential over
the other since it can cover up more
environments thereby increasing its chances
of coming in contact with the enzyme. The
end result volume-Vmax is similar the only
difference is the concentrations of the two
competing substrates taken up. As a result,
if an ALD patient was to be stuffed with high concentrations of mono
unsaturated fatty acid in the triglyceride form such as oleic acid, then the
rate at which the enzyme associates with the fatty acid would increase
greatly in contrast to saturated fatty acids. Consequently, the enzyme would
be using the un-harmful fatty acid producing long unsaturated fatty acid
instead of long saturated fatty acid chains. Finally, the biochemical pathway
ADL utilizes was manipulated and treatment was found-oleic acid as part of
the recommended diet. Lorenzo’s levels lowered.
However, oleic acid appeared to be partly effective. This became evident when
the VLCSFAs in Lorenzo’s blood increased again and a second alternative had

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to be made. Discovering that oleic acid cis double bond is very low in the
chain and to stop the synthesis of the “bad” guys the chains have to be
blocked a bit higher in the chain between C22 and C24, the doctor’s opinion
was only the mono unsaturated C22 Erucic (glyceryl trierucate) acid could be
an additional competitor against the saturated fatty acids. It is longer that
oleic acid (cis-9-Octadecinoic, C18:1). Regardless, it was considered
inconsumable to humans because it caused cardiac arrests in rats, damage to
the adrenal gland etc there was therefore no way it could be approved for
human drug trials by the Human Studies Review Committee. However, Augusto and
Michaela found it their own way and administered it to Lorenzo either way, in
conjunction with oleic acid. This is LORENZO’S OIL, in 4:1 oleic: erucic acid
concentrations and with is monitored daily administration, Lorenzo’s levels
of VLCSFAs (C24 and C26) dropped down to normal and signs of development in
his condition showed, he could swallow on his own; for starters, then gained
vision and the rest followed .However; the oil could not repair the destroyed
myelin, but could stop its further degradation. The side effect reflected
from the treatment appeared to be reduction of platelet count in the blood.
Platelets play a crucial role in blood clotting. They are the basis of
bleeding control and without them a person can bleed to death. This condition
is known thrombocytopenia.
Apart from Lorenzo’s oil and dietary suggestions, there are other therapeutic
ways of treating the disease. Even so, it is highly vital to be careful of
when the treatment is administered to a patient. For positive results, it has
to be started off at early stages before the disease takes a much more severe
course, or else the rate at which the disease progresses to terminal point
may even increase. There is bone-marrow transplant. The transplantation of
normal bone-marrow cells with the correct code for ALD-Protein into a patient
proved to increase the capacity at which VLCSFAs are degraded thereby proving
to have the ability to correct the mutation somehow. Immuno suppression is
yet another way. However, it is not as effective since its main aim is to
convert the severe form into a milder form like AMN in trial to lower the
rate of inflammatory response observed in the brain as the disease worsens.
Yet to be put into functioning and use is Gene therapy. The gene has been
isolated and proved to refract the deficiency in the metabolism of VLCSFA in
ALD cell cultured (Cartier et. al 1995). Of all these, parental genetic
counseling and family history is still the best in my opinion because it
prepares the parents, even gives them the opportunity to make a choice of not
having children give their chances, as well as allow earlier treatment
administration.
EPISODE 6

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LET’S TALK VIEWS...
With every drug development, there is a set of steps to follow especially the
drug trials step. Trials are first done with animals- rats- and if only
proven safe, the drug can then be approved for human clinical trials. It is
not an easy decision to approve drugs and sometimes that alone is a problem.
Use of Erucic acid for human consumption was not approved as it fail in
animal trials but given the pressure the Odone family felt, they went beyond
measures and used it without approval on Lorenzo. This became a problem as
there was no allowed usage and they had to be his guinea pig regardless of
any reasonable risks they were warned about such as the fact that there is no
specific set daily consumption per serving/day. This would result in over
consumption leading to even further complications such as cardiac arrests and
others. It was also argued that there is no knowledge as of to how much
Lorenzo could digest fatty acids which would in return relate to t he amount
to consume and more. Their behavior proved the code,” desperate times,
desperate measures!” they were desperate and took every chance they found.
This could have been really gone badly if this was a different case or if one
was highly allergic to it. However in using the aunt as a “rat” seemed highly
justifiable and appropriate as this was the final product and she was an ALD
carrier as well.
Human disorder are really hard to break because every step in drug
development goes against every ethical amendment, there is a lot of paper
work to handle, there cannot be a control group therefore no way to correlate
progress. I remember Prof. Bragg; he was talking about HIV/ any other virus.
He emphasized on the fact that there cannot be a volunteer to be injected
with the virus and live to surfer just for the sake of a medical
breakthrough, which is true and also the opposite would be unethical and feel
like murder and I argued that that’s him justifying why he specializes with
animals. However, it is true. Doctors have protocols and rule to follow and
they cannot take certain risks with patients hence why sometimes the parents
and society should throw in here and there a little incentive into pushing
them to the extremes like Augusto did. He actually worked hard to bring
together a group of doctors who had never worked together before, each
bringing their specialties to try finding a solution to the shaking dogs’
problem. The dogs were born without myelin and the task was to find a way to
remyelinate them. Their working together led to a fast finding of the answer
and the dogs were remyelinated and stopped shaking, subsequently so were
human trials initiated. Not only that, he also release an article which they
pushed for its publication so as to spread word and initiate interest and
curiosity in doctors which would result in their interest in the disease,
even though such researches are really expensive and require funding. This is
not a matter of ethics it’s a matter of demand, supply and profit and that
is; the reluctance in funding such researches based on facts like, they are
very rare; so does that mean they can die it’s an acceptable loss anyway?
Where are their ethics now?
LET’S TALK MY VIEWS...

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Putting myself in Michaela’s shoes, being told that I left the window open
and so were robbed scares me and I make sure that I never do it again; what
more of being told that my son is sick and dying rapidly with every passing
minute and it’s all because of me? I understand how she was feeling and so
she expected everyone to feel what she was feeling- the need to try correct a
mistake yet unfortunately this one could not be refracted, because it was not
a mistake, but nature. She was under pressure and so she released it to
nurses, family and pretty much everything that that everything that didn’t
agree with her. The advancements present now in medicine were not available
then and even knowledge and care about family histories and genetic
counseling were not of concern. What am I saying? I am saying with all I know
right now, I would have a child either being a boy or girl because there is a
chance that I may not have an affected son or even not have a son at all,
just have daughters and so I think no law or doctor should stand in my way. I
somehow think it’s about time the ministries of health take into
consideration investing in the investigations and researches of diseases like
ALD as much as they did and still do with HIV- no wonder so many people are
infected-. I intend to be a medical microbiologist focusing on human
pandemics and concentrate on researches on diseases like ALD. I know is not
viral, but been that as it may, it still remains part of the medical
breakthroughs history.
EPISODE 7
*****CONCLUSION: *****

16. [2009078425]
16
All in all, ALD is genetically inherited and cannot be controlled like an
infectious disease and even so, carrier women should not be burnt from having
children. X-linked disorders such are quite rare and their occurrence is
quite slim as well especially with recessive form. All the forms of treatment
derived for ALD focuses mainly on refracting the VLCSFA which accumulate in
the brain due a default ALD-Protein (745 amino acid long)- responsible for
their metabolism; and take back their levels to normal, and each in their own
way yet the end game is the same. This is a very severe disease even though
rare and therefore needs to be taken into consideration. There are different
forms but, childhood cerebral form is the most fast progressive form
resulting in retardation. This is due to the rapid degradation of brain
myelin sheath with time. The brain is like a computer CPU, its destruction,
there is no computer, and so this is the very same case with ALD, it destroys
first the brain and the rest is history. The general knowledge about the
disease was that its patients do not live to see even the first decade but
that was until LORENZO’s OIL, a combination of two mono unsaturated long
chain fatty acids; erucic and oleic acid; was developed by Augusto and
Michaela Odone. The oil initiates competitive inhibition which is the basis
of ALD treatment and it is based on the biochemical properties of the
disease. Given everything, it is still necessary for further researches to be
carried out and bring in new advancements on how to deal with other disorders
like ALD. Parents of affected children will always have a disagreement with
doctors whenever they try protesting any initiation of treatment. Support
groups such as ALD foundation are really important and play a vital role in
helping the parents cope emotionally in knowing that they are not alone and
by sharing ideas that may be of help for both the sick child and the parents
too.
In a nut shell; this is one of the successful researches in medical history,
only because someone was willing to go beyond and because of that lives can
be saved. All going over board and taking no consideration none whatsoever
about any ethical law finally paid up, it was not all for nothing.
NB: VLCFAs in plasma: C22:0, C22:1, C24:0, C22:1, C26:0 and C26:1
“All great and honorable actions have been accomplished with great
difficulties and both must be enterprise and overcome with answerable
courage”
- William Bradford
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THE LAST CHPTER…

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17
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