15q13.3 micro duplication questions

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Sharond
Posts: 3
Joined: Fri Oct 30, 2015 10:51 pm

15q13.3 micro duplication questions

Postby Sharond » Fri Sep 29, 2017 11:49 pm

Hi there!
I came across some old threads from Fatherof2 in my googling rabbit hole and thought I'd post here to follow up. My son has this duplication and I'm curious about how much galantamine and any nootropics helped?
It's all so confusing to read about!
My son has essentially been a "non responder" to all the typical biomed type stuff, so I really would like to look further into nootropics. We briefly tried alpha gpc when we first found out (a bit over a year ago) but admittedly never really gave more than a sprinkle. I was flying solo and wasn't really sure about dosing.

Fatherof2 or anyone else, I'd love any insight or advice or recommendations.

Thank you so much!

FatherOf2
Posts: 1592
Joined: Mon Mar 11, 2013 1:37 am

Re: 15q13.3 micro duplication questions

Postby FatherOf2 » Sat Sep 30, 2017 12:44 pm

My son has triplication in this chromosome, CHRNA7 gene. Right now, I am not doing anything specific for it. It is hard to find out whether duplication or triplication means more alpha-7 receptors or less. Duplication is considered less severe than deletion, which leads to schizophrenia, heavy smoking (nicotine is an activator of underexpressed NAchR). The fact that my son was better on Galantamine and slightly better on CDP Choline doesn't mean anything. Anyone would be cognitively better on those. Besides, the effect didn't last, we needed to cycle those 1mo ON / 1mo OFF. Nootropics in general help cognition, but I had to be careful not to make his abnormal EEG grow into seizures. The only nootropic that was studied well and shown to actually reduce seizures is Piracetam. I would recommend it to anyone without hesitation. The more stronger ones such as Aniracetam, Oxiracetam, Phenylpiracetam, Nefiracetam, Fasoracetam, Noopept, Modafinil may cause seizures or activate dopamine receptors. Besides Piracetam, Bacopa is a safe one and shown to reduce seizures. I stopped Piracetam years ago, but I am giving Bacopa now. Bacopa doesn't have a strong effect on cognition, but it does make my son less irritable and anxious. I never had any luck with Vinpocetine.

Currently on my list to try next is BH4 (never tried it, my son has MTHFR A1298C homozygous mutation) and LDN again. I tried LDN when my son was 4.5. After first couple of weeks of no sleep, he stabilized and became calmer. I don't remember seeing anything else from LDN. But, going the route of re-balancing his immune system is something I want to do considering that he doesn't get colds or flu, which clearly indicates overactive immune system, which perhaps is attacking his own organs like in many autoimmune diseases.

Sharond
Posts: 3
Joined: Fri Oct 30, 2015 10:51 pm

Re: 15q13.3 micro duplication questions

Postby Sharond » Sat Sep 30, 2017 1:47 pm

Thank you so much for your reply. My brain is toast trying to understand everything I'm reading about chrna7, etc.
it's so difficult to understand.

I've been reading all of your old posts trying to get more understanding but still feel like I'm not positive what I should be doing.

Neither of our docs mentioned anything supplement wise in this department. There's a woman I know who's had great success with galantamine and reading her blog reminded me that I hadn't really thought of any of this stuff in a while.

Can you break down in layman terms how someone with this issue is "broken"? Is it that they don't get enough choline?
I want to approach our doc with some knowledge and studies do that maybe we could try piracetam or galantamine or something.

We had an eeg a year ago. The neurologist said everything was normal minus one little thing she saw overnight that she said didn't concern her. Just that we should follow up in a year. Well, the mere thought of going through that again sounds like a barrel of fun. So do some drugs/supps have more likelihood of causing seizure activity? (Of the stuff we are discussing I mean)

Thanks again. I appreciate your time. I feel like it's not really talked about on google minus very wordy scientific articles and my brain isn't quite getting it. Lol.

FatherOf2
Posts: 1592
Joined: Mon Mar 11, 2013 1:37 am

Re: 15q13.3 micro duplication questions

Postby FatherOf2 » Sat Sep 30, 2017 3:11 pm

There are two possible outcomes of the CHRNA7 duplication: you either have too many or too few nicotinic acetylcholine receptors in the brain. Acetyl choline is a chemical / neurotransmitter that activates these receptors. Nicotine does the same thing. That is why they are called nicotinic acetylcholine receptors. The CHRNA7 mutation doesn't affect the amount of acetyl choline in the brain. However, by supplementing choline (alpha GPC or Citicoline) or by creating more acetylcholine (through Galantamine, which prevents the breakdown of acetylcholine) you can affect the activity of acetylcholine receptors. So, if CHRNA7 duplication causes fewer receptors than normal, you can make them more active than normal by these supplements and counteract the mutation. If CHRNA7 duplication causes more receptors than normal, then adding choline would still activate them more than normal, you may just have a much stronger effect.

Here is where things get fuzzy. Brain changes the number of receptors all the time to maintain the signal through them constant. By signal I mean the amount of ions that enter the neuron through an open receptor (opened by acetyl choline). Think about a receptor of a neuron as a sink faucet. A neurotransmitter (acetylcholine in this case, or glutamate, or GABA in other cases) is a hand opening the faucet. Ions entering the neuron is a water filling the sink. Once the sink is filled with water to certain level, it acts (the neuron fires - creates an electrical impulse that propagates through the neuron tail towards other neurons). If you have too many faucets (receptors), the water (ions) will fill the sink (neuron) much faster and make it fire more often. You get hyperactivity or seizures. But too many faucets will only be a problem if there is a hand (neurotransmitter) available to open each one of them. So, you can control the activity of the faucets by adding hands / neurotransimtter (through choline supplementation for example) or subtracting them (by increasing their breakdown - esterase). So, apparently brain would try to counteract any changes to the signal (amount of water / ions) entering the sink / neuron. If there are too many hands/ too much neurotransmitter, it will reduce the amount of faucets / receptors and vice versa. This typically happens within few weeks. That is why most supplements or medications affecting neurotransmitters or receptor activity act temporary - you build up tolerance, which means that the brain counteracted changes by creating more of fewer receptors.

So, back to the CHRNA7 duplication. I asked several doctors what does it do to receptors. Nobody knew. One joked that if I had millions of dollars, I could hire a company who would collect my son's stem cells, grow receptors in petrodish and then tell me exactly what happens to receptors. In the end, it really doesn't matter because regardless how I change the activity of these receptors, brain would always change things back to 'normal' by changing their number. The only permanent way to fix it is to edit DNA to remove the mutation, which is an emerging treatment (read about BlueBird Bio)

Marya
Posts: 158
Joined: Tue Feb 21, 2017 4:14 pm

Re: 15q13.3 micro duplication questions

Postby Marya » Mon Oct 02, 2017 10:45 am

FatherOf2 wrote:There are two possible outcomes of the CHRNA7 duplication: you either have too many or too few nicotinic acetylcholine receptors in the brain. Acetyl choline is a chemical / neurotransmitter that activates these receptors. Nicotine does the same thing. That is why they are called nicotinic acetylcholine receptors. The CHRNA7 mutation doesn't affect the amount of acetyl choline in the brain. However, by supplementing choline (alpha GPC or Citicoline) or by creating more acetylcholine (through Galantamine, which prevents the breakdown of acetylcholine) you can affect the activity of acetylcholine receptors. So, if CHRNA7 duplication causes fewer receptors than normal, you can make them more active than normal by these supplements and counteract the mutation. If CHRNA7 duplication causes more receptors than normal, then adding choline would still activate them more than normal, you may just have a much stronger effect.


Hi @Sharond and Fatherof2, Sorry to interfere here but I would add something that may beneficial for anyone here. I have CHRNA5 mutation which leads to less Neuronal acetylcholine receptor subunit alpha-5. Both Nicotine and Acetyl Choline would activate it as Fatherof2 mentioned. I'm not sure though if I have less receptors or less neurotransmitters but in general by supplementing CDP-Choline I'm feeling very well. From my symptoms I think CHRNA5 caused more than cognitive issue. I was feeling fearful until I've started taking Choline, on the 3rd day all the fears are gone. I've started taking it 5 weeks ago and I'm still feeling well. Also my cold(sweated) hands and feet are nicely dry since then. My cognitive definitely is better. All that making me confident and happier. I'm only taking a single dose of 250mg but I'm thinking to recycle it on/off. The recommendation dose is 500mg though but I don't want to disturb the receptors. I have another option which is Nicotine but who wants a lung cancer risk?!
I cam to the conclusion that Choline deficiency along with other vitamins caused delay in central nervous system development. That's how it is recommended for women during pregnancy to avoid Schizophrenia and other mental illness in infants.

Marya
Posts: 158
Joined: Tue Feb 21, 2017 4:14 pm

Re: 15q13.3 micro duplication questions

Postby Marya » Mon Oct 02, 2017 12:52 pm



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