I found this posting of someone's theory about how eating wheat affects those with HD. Could someone who understands the biology comment?

Link:

[thepaleodiet.blogspot.com]

Copy:

Question: I just listened to an interview of Cordain. He mentions that Huntington Chorea seems to be an autoimmune disease. I have Huntington Chorea in my family. So obliviously I'd like to know more about your or his findings. Could you please explain if there is any study showing this and what foods one should eliminate from the diet? I'd be so grateful.

Thanks,
Tim

Answer: Hi Tim,

Huntington's Chorea or Huntington's Disease (HD) results from lesions (alpha synuclein crosslinks) occurring in the brain which cause the characteristic symptoms (tremors and paralysis) of HD. It is well documented that a genetic basis underlies the development of HD. HD patients inherit a specific gene which causes increased expression of a protein called mutant huntingtin protein (mHTT). Whereas people without HD have inherited a gene which expresses the normal version of this protein, simply called, huntingtin protein (HTT). The over expression of mHTT at the expense of HTT is thought to cause the brain lesions of HD.

So, can diet have anything to do with whether or not a person with the mHTT genetic makeup goes on to develop the disease? Yes, and let me explain the underlying rationale. The imbalance in the mHTT to HTT ratio that occurs in HD patients requires the inheritance of the mHTT gene, however the gene cannot make its product without the presence of an enzyme called transglutaminase (TG). Transglutaminase is a post-translational enzyme (meaning that it is required to produce the gene product after the gene has been translated within a cell's nucleus). TG is a ubiquitous post translational enzyme that is found throughout the body's tissues, particularly in the gut, nervous tissue and brain. Without the presence of adequate concentrations of TG in the brain, mHTT cannot be produced in sufficient quantity to imbalance the mHtt to HHT ratio that results in HD.

So the $64,000 question in HD: what is the environmental trigger that causes over expression of TG in the brain? Plain and simple, it is wheat. More specifically, a storage protein in wheat called Gliadin. Unlike other dietary proteins, Gliadin is an unusual protein because it is resistant to the enzymes in the human gut (proteases) which normally degrade proteins into their constituent amino acids. Consequently, Gliadin arrives in the small intestine intact where it has recently been shown to bind a gut receptor (the CRX2 chemokine receptor). When Gliadin from wheat binds CRX2 it causes the intestinal cells to release a recently discovered enzyme known as zonulin. Zonulin release by gut cells causes the gut to become "leaky" and allow passage of intact proteins across the gut barrier -- including Gliadin itself.

Once Gliadin bypasses the gut barrier, it is immediately catalyzed by transglutaminase (TG) which is expressed by local intestinal cells. When you eat wheat on a daily basis, there is so much dietary Gliadin bypassing the gut barrier that it overwhelms the ability of the intestinal cells to produce the enzyme (TG) to catalyze the substrate (Gliadin). Intestinal cells as well as all other cells in the body react to this overload of circulating Gliadin by up-regulating (increasing) TG production.

The proof of the pudding lies in the experimental evidence. Unfortunately no randomized controlled trials of Gliadin free diets in HD patients have been examined to date. Having said this, I am aware of a single HD patient in S. California who was a member of a local CrossFit Gym, and who had been diagnosed with HD by a group of University neurologists employing MRI technology to detect the characteristic brain lesions. After approximately 8 months following adoption of a Paleo Diet (Gliadin free), this patient experienced a dramatic reduction in disease symptoms and subsequent MRI evaluation indicated a reduction in lesion volume. In addition to HD, numerous ataxia patients respond favorably to Gliadin free diets.

Cordially,

Loren Cordain, Ph.D., Professor

Hmmmm, can't explain the biology... but it's not the first time some unnamed person was examined by some unnamed doctor who was "better" by using the latest cure-all of the day. Not exactly responsible reporting. That indicates someone with an agenda other than HD to me.

This connection has been suggested before. I recall a report of a high percentage of HD patients who also had gluten intolerance (one doctor or one clinic, I forget). I believe it might have been 40 percent. Since this could have coincidence in a fairly small group of people, Swedish scientists searched their medical database for the population and found that there was no association between celiac disease and any of the neurodegenerative disorders, including HD. However, celiac patients may experience neurological damage especially if they have allowed their disease to get out of control.

I do not fully understand the answer in the original post. I know that wheat has in the past been linked to a number of different disorders specifically schizophrenia. Wheat is one of the more common food allergens but still only a small percentage of the population is actually allergic. However I have heard different numbers for population intolerance ranging from 15% to 30%. A large number of people with wheat intolerance never realize that it is a problem because the symptoms can be mild and are not perceived because of their daily occurrence. The 40% that Marsha suggested would indeed be high. An actual allergy to wheat can cause symptoms that mimic HD symptoms. So it would make sense to me that someone with HD and a wheat allergy who cut wheat out of their diet would perceive the HD to get better. I do have a paleo friend who believes no one should eat wheat, so perhaps I will go seek out a lecture on how our bodies do and do not process wheat and get back to you with more info.

Hi Guys,


The way Loren Cordain speaks doesn't inspire much confidence.

HD is not caused by "alpha synuclein crosslinks". Alpha synuclein is a protein that is found in a type of lesion in the brain called "Lewy bodies". HD patients have aggregated protein in their brains, but it's totally different than Lewy bodies, and no biologist who knew what they were talking about would confuse the terms.

Secondly, HD is not caused by "increased expression" of the mutant huntingtin gene. We've known since about 1995 that there's no change in the actual amount of mutant huntingtin, relative to the normal huntingtin, it's just that it's mutated. It's the mutation that causes the disease, not increased expression of the mutant gene.

I could go on, but it doesn't get any better. Based on how wrong he is about HD, I wouldn't put much faith in it.



jeff



Jeff Carroll
Centre for Molecular Medicine & Therapeutics
University of British Columbia

P: 604.875.3825
F: 604.875.3819
E: jcarroll@cmmt.ubc.ca

Thanks for clearing things up. Too bad it could not be that simple.

On my highschool biology knowledge, the first thing I wondered when I read about the HD protein was whether we could simply avoid eating a key amino acid. But of course it cannot be that simple either.



Edited 1 time(s). Last edit at 05/12/2010 10:59AM by smiling sara.

I am not gonna put much stock in this at all. Some people put no stock at all diet and exercise. Others are totally "sold" on it. I imagine there probably is some complimentary diet or lifestyle choices that will aid in management of HD. Or at least some that work against management of it. But not unlike diabetes, or high blood pressure, or heart disease... medical intervention is going to be the true answer to HD. Like all those things you can do it the easy way or the hard way and compliment the intervention or not.

I remember going though the phase where I looked for the closet genius who had some hidden answer to HD. The fact is there are regular old geniuses working on HD... and the process of genius working with genius is where HD will be unraveled. And no one is going to solve HD in the basement or their living room. This gene, untreated, is going to try and express itself. It's going to take money and sweat equity to get as close to what it is expressing and cut it off. It may be several thing that need to be shut off and it also has to not cause more harm than good in doing so. There is not going to be a cheater way around HD. If you want to really see an end to HD people have to participate in HD in the here and now, make HD a comfortable topic, work hard to help those who need it now and work hard for the people of the future. Googleing HD endlessly really won't help. I wish it would... I have and like google...

All this stuff though always comes back to me as HD and family. HD should give you purpose in life... it is devastating at times to your family. Yet not all people find purposeful reasons to act. To me that means someone isn't doing something right to offer people the various things needed to find purpose. Everyone enters the community looking for help of some kind... answers, understanding, and whatnot... but so many don't stay. If you don't raise money, don't understand science... what purpose do ya have in the community? Does HD as a community have purpose? Or better yet many purposes? It should.