Dr SB Prusiner considered that the individual prion is the sole agent of BSE/CJD. Soon it was realised, that this is a normal house keeping protein, present in all animal species tested so far. The protein contains 254 amino acids, however, it is important to remember, that there are differences in the amino acid sequences among species. The protein is expressed giving rise to the same primary translation product in normal and infected brain.

Role of Mutations in the PrP gene: Once it was realised that the PrP was host derived, a search began for differences (mutations) in the corresponding human gene, among affected families. It has been suggested that these point mutations observed in the PrP gene may cause the disease. The first was found in codon 129, and subsequently in codons 102, 117, 178, and 200. There are reports of other mutations in codons 51 and 118. Apart from variable point mutations seen in different families cases, these mutations have been seen in a number of first degree relatives of affected patients who are healthy into their 60s and even mid 70s. These mutations in the PrP gene in some patients may be important because, the mutation may reflect an increased susceptibility. Sporadic CJD cases, which form the majority, do not have these mutations.

From all transmission studies it has been well established that the replication of the infectious agent starts after inoculation of a new host species, which may have a different genetic makeup of the PrP (amino acid sequence) as compared to the original host. Monkeys or chimpanzee inoculated with human-infected tissues have no PrP gene mutations, similar to those in human brain material infected with CJD or Kuru or BSE. None of the point mutations are copied in the PrP gene or its product in the new host. Further, when BSE tissue containing the agent and bovine PrP27-30 is inoculated into sheep, the affected host sheep modifies PrP33-35sh into PrP27-30sh. Similar results are obtained by inoculating BSE tissue containing PrP27-30Bo into mice, pigs and goats, where host PrP33-35 modifies into respective host PrP27-30. The strain of the agent "breeds true", retains its original properties during the passage from one animal species to another. This clearly demonstrates that these strain differences cannot be contained within the host-coded PrP molecules do not "breed true".

Prion does not control susceptibility

Based on their response to the scrapie challenge, sheep genotype is divided into "positive" (susceptible) and "negative" (resistant) lines. Comparative experimental transmission studies using brain extracts, collected from natural scrapie sheep and BSE- to sheep of different genotypes, unexpectedly, revealed different patterns in incubation periods between transmission of BSE and sheep scrapie to mice and sheep. Both the "positive" (susceptible) and the "negative" (resistant) lines of sheep developed the clinical disease through both i.c. and oral transmission of the agent of BSE. These comparative studies clearly demonstrate gene plays no role in the outcome of susceptibility, or on the incubation period with the BSE agent. The incubation period in BSE is preferentially being influenced by the strain of BSE agent, which has a major influence on the outcome.

Further experimentation particularly using the BSE agent, it is obvious that the incubation period is an interaction of host and strain of the agent and not just influenced by the genetic make up of the host PrP gene, demonstrate that the disease is not a genetic disorder. These findings also suggest, that a normal PrP by itself is not the agent.

Humans have no protective gene

As we are aware that DNA exist in a pair and at a particular site in the PrP gene called codon 129, humans can have the pair as methionine - methionine (Met - Met); or have a pair as valine - valine (Val -Val) or combination of the two, that is, Met - Val). The patients classified under nvCJD had pair combination at codon 129 Met -Met, which is found in about 30% of the population. Knowing genetic make up of patients those who had been treated with human growth hormone and also results of experimental transmission of the BSE agent has revealed, that host genes have little influence in the final out come of the clinical disease. Dr John Collinge suggested that humans those who have Met - Val or Val -Val combination in codon 129 have the protective gene.

Now having learnt that all 11 kuru patients studied suggest that all have Met - Val combination and it appears that people with protective gene combination are not immune from the disease. They simply will have to wait longer for the disease to stick.

Strange it may sound, some think kuru is not the same as nvCJD, but how different, Kuru was caused by Type II scrapie and so was BSE and nvCJD

 

TwoLetter from Elaine

AND

Reply from Harash

Dear Elaine,

Thanks for your email. The nesw is good and exciting that you are well now. I am not sure, if you had CJD. There is a big differrence what you suffered from to what is CJD? As you said, the treatment with B1 vitamin injection has helpded, Bs' are ecential to release energy within a cell, obviously without vitanin Bs' cell would starve. I am sure relatives of CJD patiens are aware of the benifit of vitamin Bs'. However, in CJD it is infection, a parasite, which utilises prion, a normal host cell protein to make its own nest, and eventfully starves it. Death of of cell means cell is gone for ever.

Harash

Dear Dr Harash Narang,
I believe I've found a simple reason why prions misshappen/missfold to cause brain wasting illnesses. Research found a reasonable explanation in the Encyclopaedia Britannica.
I've also found a simple treatment used in the treatment of a brain wasting disease in livestock, which has similar symptoms - give or take a few and put into human terms - as CJD. I've discovered why and how it works.
 
Why am I interested? 
I'm just a little old Grannie from a farm in the Australian bush. Our sheep were diagnosed with a brain wasting disease in 2001 - I had a similar symptom.
After 2 months, I bought the treatment - also for human use - which suppressed the symptom within  minutes - for a few hours.
I began to display other horrific symptoms - which research found - were similar to neurological symptoms, which crossed over many different illnesses and conditions - including CJD. These symptoms were also suppressed by the treatment.
 
I experimented - with other simple things which also worked the same - so it wasn't what I took, but how it worked in my body which mattered.
After 18 months of experimentation, research, trial and error, my horrific symptoms started to reverse. I have reasonably good health now - most of the time.
I found that the sheep and my cause of illness were different - but our symptoms were very similar - and the  treatment saved my life.
Our several ill sheep died  before they could be treated. This treatment for a brain wasting disease in livestock, was known about before 1968. I wonder why humans aren't being treated with it.
 
I wonder if you would be interested in my research and findings.
Regards

Dear Harash,
I presume you would like to know more -
No, I can't say I had CJD - I was never tested for it - I asked about testing - but as it involved a lumber puncture, I didn't have it. I developed many neurological symptoms similar to our sheep - which I've found are also displayed in many human neurological illnesses and conditions.
 
Our sheep were diagnosed as with PEM - Polioencephamolacia - a brain wasting disease.  It's supposed to be caused by BV1 deficiancy. But I believe the cause of our sheep's illness was from grass which can be very toxic at certain times of the year - in our Autum. 
My symptoms, I believe were caused by injury to my head and spine in a tractor accident (on top of fused neck vertabra in an accident as a child) years before the symptoms became worrying. Research found that if there is injury to the carotid body (I didn't even know we had one of those), it can cause an imbalance of carbon dioxide and oxygen to the brain. I believe this could be the cause of those CJD cases where there is no known cause. Several case studies of people who died of CJD, of unknown cause, mentioned falls and injuries to the head and spine.
 
The successful treatment for PEM (known about before 1968) is injected Vitamin B1.  I  found - and rang the Australian vet who put the treatment info into a journal in 1968. I asked him why the VB1 worked. He didn't know. I bought VB1 in tablet form.
 
Through my research - experimentation and documentation, I've found the VB1 dose increased my temperature, my heart rate, my breathing - all as if excercising - , increased blood circulation and oxygen circulation and content, to the whole body, tissues, cells, organs and also to the brain.
 
I believe prions are an anaerobic. Info in the EB found that the sickle-cell of sickle-cell aneamia looked normal - until exposed to oxygen - then the cell changed formation. Take away the oxygen, and the cell reverted back to a sickle-cell.
Prions and many other "bugs" (many probably haven't been found or named as yet) which make us ill, could be anaerobic, part anaerobic, have an anaerobic cell or need a host which is one of the above. 
 
Our sheep and I displayed similar neurological symptoms - similar symptoms to CJD - why not similar treatment?
I believe I would not be here now if it wasn't for the diagnosis of our sheep - and the treatment information. Doctors wouldn't believe my symptoms - nor my research, findings or treatment. They were not the ones battling to survive - they were not the ones having seizures, spasms in the spine, horrific cramps throughout their body, hurtful twitches and tics - and many more symptoms too numerous to mention.
 
By  experimentation, I found the right VB1 dose quantity and dose rate for my body weight. My horrific symptoms were suppressed within minutes of each dose for a few hours. This treatment repaired damage to my nervous system due to  injury - and/or toxin - as I also had high Cadmium detected in a medical test. Several other people with all sorts of illnesses and conditions, - even with Parkinson's - said they had better health whilst taking what I suggested.
 So it wasn't just a fluke that I  got better - I might add - with a whole lot of determination to survive - when the chips were down.
 
I'd like to know what your thoughts are on my findings.
Regards
Elaine