Folks considering minocycline for the treatment of HD should be aware of potentially dangerous side effects for HD patients.
Patients taking minocycline frequently complain of vertigo. Vertigo is a disordered state in which the individual or the individual's surroundings seem to whirl dizzily. This could lead to falls and injury.
Under some conditions minocycline may accelerate HD.
Jerry 05/19/99; updated 12-Jul-2001
From: Arzneimittelforschung 1987 Aug;37(8):950-3 Schneider D et al.
An equilibriometric study has been performed on 20 healthy young women before and after the intake of 7 times 100 mg minocycline during 3 days.
A systematic neurootological equilibriometry was performed analyzing the vestibular ocular, the vestibular spinal, the retino-ocular and the spontaneous nystagmus pathways.
The results demonstrate that the tetracycline minocycline provokes a ponto-medullary liberation of the central vestibular regulating mechanisms. The central vestibular disinhibition could be exhibited by the monaurally elicited vestibular ocular nystagmus as well as by the radar image like cranio-corpography recordings of the head and body movements during a vestibular spinal stepping test.
In parallel with these findings the participants of the study increasingly complained about vertigo of the rocking type, instability, malaise and wretching.
Thus, the untoward side effects of a tetracycline like minocycline which is a frequent complaint of the patients, appears to be due to a central disinhibition of the vestibular equilibrium regulating mechanisms.
| If this carries over to humans, it leaves the pHD and his caretakers with an interesting choice: progression as we know it vs. many years of slower progression followed by a crash. |
At the convention, the researchers spent considerable time giving their versions of what happens in HD-affected neurons. My understanding of what they're saying is:
The neuron has 2 copies of the HD gene, one with expanded repeats. The neuron needs to have these genes expressed--i.e., have the genes guide the production of the protein, huntingtin. RNA does this. It sneaks up to the genes, reads their blueprints, and uses those blueprints to create huntingtin--good huntingtin from the the normal gene, bad huntingtin from the one with expanded repeats.
Glutamine is present in both forms of huntingtin, I suppose one chunk for each repeat. At any rate, something in the neuron senses the abnormal number of residues in the bad huntingtin, so that triggers caspaces to go in and start cutting the bad huntingtin into pieces, destroying it so that it can't screw up the works. These pieces (and other garbage in the neuron) clump together into the aggregates, and this is good because it gets the garbage out of the way so that the neuron's machinery can continue to function.
However, as more and more junk gets aggregated into the clumps, some good stuff wants to join the party and jumps on the clump, too. That means the good stuff isn't available to keep the machinery going.
That's not the whole story, though. The caspaces are having so much fun cutting up the bad huntingtin that they go on a feeding frenzy and attack the good huntingtin, too, stopping it from doing whatever it's supposed to be doing, and making more pieces that get stuck in the clumps. Eventually, the clumps get to the point where they start doing more harm than good, and then the machinery gets gummed up and stops working and the neuron dies.
The complexity of the HD neuron death process is even more than I described. There seems to be evidence that, before the pieces get aggregated, they interfere with the operation of the machinery. (Presumably, preventing the clumping would lead to even-earlier cell death.)
Thus, there are lots of pathways in the process of HD cell death. That's good, in a way, because, it may mean that lots of different medications may be useful, each one targeting a different pathway. It's bad, though, in that the pHD may be required to take a cocktail of medications, each targeted at a different pathway (and, perhaps, each with its own set of side effects).
Caspace inhibitors, e.g. monocycline (sp), affect only one of the pathways. They do help, but eventually, the cell dies anyway. One of the researchers told me that, in mice, the progression of the disease is slowed significantly, but that eventually this slowing process stops and then the deterioration is rapid. Thus, in mice, gradual deterioration is traded for even more gradual deterioration up to a point and then a crash. If this carries over to humans, it leaves the pHD and his caretakers with an interesting choice: progression as we know it vs. many years of slower progression followed by a crash. (If it were me, I'd probably choose the latter.) Of course, if more cocktail ingredients become available, the crash may be mitigated, too.
I suppose that if a way were found to prevent the bad huntingtin from being expressed, then the cocktail approach would no longer be needed, or at least not needed to deal with the cascade of nasty pathways involved in HD cell death. Other medications might be needed to deal with side-effects of whatever prevents huntingtin from being expressed. I don't know how the expression of bad huntingtin can be suppressed without also suppressing the expression of normal huntingtin, but our scientists are pretty clever people.
Tom Caldwell Posted on HUNT-DIS 12-Jul-2001