an ALS Hypothesis - extended to all 'abnormal' neural atrophy

John H. johnhkm at netsprintXXXX.net.au
Wed Feb 2 07:35:56 EST 2000

<dag.stenberg at helsinki.nospam.fi> wrote in message
news:8766kn$bad$1 at oravannahka.helsinki.fi...
> kenneth Collins <kpaulc at earthlink.net> wrote:
> > i've reformatted my prior post to make online reading easier.
> Ah, now it is all right.
> Most points in your previous message are now clearly explained.
> I think that (descrambled) hypothesis is quite worth to read. It may be
> way off road, but at least the details and reasoning deserve thinking
> about.
> > the main thing that stimmed this 'dietary' stuff was with respect to the
> > problem represented by the 'late onset' of the disease conditions, which
> > needs explication. if, in accord with the traditional view, it actually
> > is the case that a single DNA mutation results it the entirety of the
> > disease condition(s), then why is it that the stuff of that mutation is
> > activated in such a delayed way?


> For comparison: in prion diseases, it takes times for anomalous PrP to
> develop and for deposits to accumulate.
> > >> i relied on the discussion of ALS in Kandel, et. al. for my
> > >> start. the factors that i found significant are as follows.
> > >> the Hypothesis:
> I had not earlier been able to find this among the over-long lines.
> > >> the demyelination results from a specific brain stem lesion,
> > >> of a type analogous to the chemically-induced vestibular
> > >> lesion, or a stroke-induced lesion.
> > >> ...
> I do not see any explanation for the fact that brain stem symptoms are
> usually later in appearance than limb involvement. It also seems to
> neglect observable peripheral pathology.
> > >> there are other attractive rationales for this sort of
> > >> hypothesis. the problem of the 35+ years typical onset of
> > >> ALS has to be explained. if there's a genetic flaw, then how
> > >> is it that it shows itself only after 35+ years? what's the
> > >> 'switch' that changes fully-functional motor neurons to
> > >> dysfunctional 'motor' neurons?
> Interesting question, no doubt.

Remember Huntingtons, 45 copies or repeats and away it goes, but that takes
until middle age, although non symptomatic pathology is present for quite a
while. I don't see these things as turn on\turn off objects. There is a
battle going on here but time gives pathology the inevitable edge. The
question of late onset does not concern me too much. I suppose my view is
that the brain begins with a head start (literally) but time eventually
takes its toll. Live long enough and we'll all be fascinated by Teletubbies.

> > if this sort of thing occurs, then the disease is treatable through
> > methods that eliminate the functionality of the newly-triggered stuff,
> How would you diagnose the disease 35+ years before outbreak?

> > at any rate, an explanation for the observed delayed onsets of
> > Alzheimer's, ALS and Huntington's is necessary, and it will probably be
> > the case that, when such delayed onset is explained, treatment
> > strategies will become apparent within such explanation. so explication
> > of the delayed onset is an important problem.
> > >> the one criterion that =must= be met in order to explore
> > >> this hypothesis further is, since the ocular motor system is
> > >> not affected in ALS, to culture examples of ocular motor
> > >> neurons  along with examples of upper and lower motor
> > >> neurons, and look for differences that would allow the
> > >> ocular motor neurons to survive while the upper/lower motor
> > >> neurons would not survive.
> This seems to me a profitable approach. Objections, anyone?

Thanks Ken, I wasn't aware of this. Another item for the database. Can you

The differences you may need to find could take forever. Interesting idea
though. Practically I have no idea if the two cell types can be in suitably
similiar cultures and even if possible the setup may mitigate the benefits.
The problem may lie outside the cells. Transporters? It may not be anything
specific deficit, a subtle allele that tips the balance, this or that
doesn't work so well over time and it's just going downhill faster. The
brain is a chaos fighter, but some brains just can't win against some chaos.
I can't see any switches, I'm running with James Clerk Maxwell on this one,
"The laws of probability is the true logic of nature."

Need to know exactly where the ocular muscles receive innervation. Eg. v.
close to eyeball, on or very close to its surface. Perhaps the ocular
nerves, being that close to the CNS, receive a relatively rich supply of NGF
or acetycholine, thus prolonging their life. Perhaps very late in ALS there
is motor ocular pathology.  (help with neuroanatomy!)

Vaguely, remember reading something about eyes being "immune privileged".
Not sure what that means and know it refers to inside the eyeball, but I do
wonder if it may be relevant.

> > i repeat, i'm taking this position in this hypothesis because all of the
> > so-called 'indicators' that i've read of can result from excitotoxic
> > activation, which means that it's possible that the 'indicators' are
> > nothing of the kind, but 'only' by-products of a
> > more-globally-correlated set of dynamics, such as those that i've been
> > discussing in this hypothesis.

I'm not sure that AD is a result of excitotoxic activation. I am much more
inclined to think of each pathology specifically, from what I've seen lately
the exact opposite can also initiate cell death: excito nothing. Nerves
cells need innervation. The middle way?


> Logical. Not necessarily true, but logical.
> > anyway, that's my contribution(?) to the efforts to extinguish these
> > diseases. i could do more, but despite the fact that i've done this
> > stuff at my own expense, i've only been 'ridiculed' for having tried
> I think this (descrambled) hypothesis is quite worth to read. It may be
> way off road, but at least the details and reasoning deserve thinking
> about.
> Dag Stenberg

More information about the Neur-sci mailing list

Send comments to us at biosci-help [At] net.bio.net