Friday, April 26, 2013

Eureka! My crabbiness has nothing to do with any situation or person but everything to do with how I feel about myself.

     So, lately I found myself feeling a bit down and crabby. I;ve been trying to figure out why I am feeling this way.  Given, Luki has recently been diagnosed with autism might have something to do with it.  But, I know he is a very special and intelligent soul in a somewhat different body from other people and  I am at peace with his condition - so long as he doesn't develop seizures and have other health issues.  This is just how he has decided to manifest into this world in this particular lifetime and what an honor it is that I have been chosen to be the mother to such a brilliant soul.  I thought maybe it had something to do with Gabe as I have been feeling short with him on trivial things.  After reflecting a bit, and perhaps with some inspiration from Spirit, I had the understanding that this negative feeling which I have been projecting outward has nothing to do with something outside of myself.  In fact, it is a negative feeling I have toward myself which gets displaced onto things/people outside of myself.  This understanding must have come from above or, I am getting better at understanding myself and how I tick, or both.   Perhaps, discernment like this comes with maturity and age - I am getting old (er).  After having realized this, some of the negativity dissolved away.  It was a pity party for myself and a bit of low self esteem (which may explain why I have been  shopping for clothes so much lately) which my mind was trying to blame on other people and situations. After this realization, I found peace again with my husband and my situation with Luki.  Living in this physical world will always give me  low grade anxiety even with all the faith and trust I have developed over the years for God.  The three dimensional physical plane is not an easy classroom.
Now, the dilemma remains: how do I find more self esteem and peace with myself?  Is it possible to generate that from within or does it need to be given by someone (force) outside of myself?  I fret that I will be treated less than by other people because of my son's condition.  I worry I will not be able to relate to normal people if our situation  make us live a very differnent lifestyle.  I wish I had all the self confidence and "I don't give a crap about what other people think" attitude.  But, I know me.  I worry ALOT about what other people think about me.  I always felt like an outsider my whole life and have tried to blend in with whatever group I am with and when that was not possible, it always hurt.  We all want acceptance and inclusion, isn't this normal? Don't we all feel this way?
What is the lesson in this situation?  Find contentment with my authentic self and don't worry too much about being accepted or being a people pleaser. This is a hard lesson for me and I know my son came into being to help me master it.

I spoke with Michelle Whitedove again on a radioshow.  She just reiterated how special Lucas is and that I am worrying way too much.  She suggested I send him to Montessori and help him with vissual and hand coordinated activities.  She said he was going to surprise me and that he was an evolved being here to share unconditional love.  I love him so much and am so grateful to him.







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Saturday, April 6, 2013

ABA, Gargus and Research Ideas.

Yesterday, Luki got his first ABA evaluation.  It was pretty lengthy and comprehensive and he has another one on Wednesday.  It was so sad to answer "no" to so many of her questions.  "Does he feed himself? Does he play peekaboo? Does he point to things? Does he say mama or dada? Does he acknowledge his name?" No, no no and no.  To me, Luki is perfect, but after having answered no to so many of these questions, it just reminded me of how very different he is from regular babies.  I worry that the ABA program would be too harsh for him or that it would give him OCD.  But, I know at this time, this is the best for him.  He gets very frustrated and stressed when he is made to do things and I hope the program does not stress him out too much.

Last Wednesday, I also had my first meeting with Dr. Gargus and G. Calvert to discuss future clinical trials for the IDIC 15 population in the Alliance's registry.  He stated that he is interested in looking into a mitochondrial connection to autism, calcium channelopathy and plans to purchase sophisticated EEG machines and conduct sleep studies - all very relevant to Luki's condition.  When I brought up my concern about a possible lipid metabolism problem, he stated that his group is working on a lipid molecule from marajuana that seem to reduce autistic behavior.  I am looking forward to more research and results for testing of this molecule - eicannocannibus?  can't remember the exact name. Although the IDIC 15 clinic was just launched at UCLA, Dr. Gargus said UCLA has a much smaller autism research and treatment center compared to UCI and it caters to wealthy families that may not even need insurance to pay for services.  This was one concern I had about taking Luki to the new IDIC 15 clinic.  How much would it cost us as it would have to be out of pocket since UCLA is out of Kaiser's hub of providers. 

We invited Dr. Gargus to the annual scientific conference at UC Davis Mind Center and he hooked us up to Dr. Kimonis who is heading up the Prader Willi study at UCI.  I hope to meet or speak with her in the near future. 

I question if I am doing everything I can for Luki and wonder if he knows how much I love him.  I wish I could have him just say one word for me now - and an "I love you" would take me over the moon.  I wish he can tell me what bothers him, I would like to know so badly. 

Last week, I also suggested a research idea to the scientific advisory board which involved a possible inhibitor study of UBE3a gene product.  I suggested various ubiquitin ligase inhibitors be studied and assayed on  IDIC 15 brain cell lines, then given to the knock in mice and measure any improvement in autistic behavior.  I was told by Dr. Chamberlain that there are three kinds of ubiquitin ligase inhibitors and the one we are looking for (with a HECT domain) has not been discovered, yet.  This inhibitor has become my holy grail.  In the meantime, it doesn't stop us from trying other experiements on the nature of UBE3a.  Perhaps the ideas I am about to share have been tried and studies already, but if not, it is worth taking a look at.

First, I am curious to know whether the UBE3a gene products in IDIC 15 brain is stucturally and functionally the same as normal UBE3a.  Dr. Reiter's finding that the copy number dosage does not necessarily correlate with the severity of the symptoms suggests that there may possibly be a defective translational product in the presence of the extra UBE3a genes.  Could it be that the translational product of UBE3a undergoes a protein misfolding in the presence of the extra genes such that they do not perform at the same level as the UBE3a from those with a normal copy number?  Do the  subunits dimerize? trimerize? or just look and function differentlyand less efficiently than the normal enzyme?

I am wondering if it is possible to isolate the ubiquitin ligase form the IDIC 15 brain cell line (without alterring their endogenous structure in the process), and then run it on a gel to separate by size and charge and compare it to ubiquitin ligase from a normal copy numbered brain cell and see whether they actually do have the same characteristics.  Could we get even further confirmation through x ray crystallography to see the structure? 

If the gel study shows that the IDIC 15 E3 ligase indeed is different from the normal, what would be the effect of giving these cells more of the E3 ligase that functions properly?  I wonder if such a study is being done for the Angelman Syndrome. 

On the other hand, if the gel study shows that it indeed is the same as the E3 ligase in normal people, then rather than waiting for the discovery of a HECT domain UBE3a inhibitor, why not use the endogenous substrate for the enzyme, which I believe is an ARC protein. What would be the efffect of giving more of the ARC protein?  Could the ARC protein be modified so that it somehow irreversably binds to the UBE3a ligase (maybe form a strong covalent bond somewhere on the enzyme) so that the enzyme can no longer uptake more substrates thus rendering it inactive?

These are some crazy ideas I think of in the middle of the night and I hope to present them to the science advisory board.  Hopefully, it doesn't sound too far fetched and I don't offend anyone's scientific sensibilities.  If nothing else, they can get a good laugh at it.