Friday, June 14, 2024

NPC Parents Theory Forum


Theory Forum

The "Theory Forum" is an area of the website dedicated to parents who have NP-C kids so that we can share anecdotal information with each other.  As parents with NP-C kids, we are living in a clinical trial situation each day.   We are all trying various measures to stop this horrible disease.  We also need the world to know who we are and all that we are doing to fight this fatal disease.  We want to hear from all of you from around the world who have NP-C kids.

Specifically, we want to focus discussions on potential therapies that may or may not be working in our children.  What types of medications or herbs are your trying in your kids, what you are noticing about your children’s behavior when you try new things, what is the rate of progression of the disease?   There are a few topics listed below to get started.   If you would like to add a topic that is not listed, post it in box below and we will create a new category.

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  1. Nancy Trombley says:

    I just briefly skimmed the Brown and Goldstein research you posted on this website and this is a tremendous breakthrough as they discovered that NPC1 has a specific binding affinity to 25Hydroxycholesterol . This relates very well to Dr. Ory’s research I commented on just previously as this is similar to the product he used in his research.

  2. Nancy Trombley says:

    Hi, my name is Nancy Trombley. I want to thank you for this forum, as I was wishing of one for a long time, but computer savvy is definately not my strong suit. My daughter Michelle was diagnosed at 15 and is now 21. Like Chris, I was determined to research and find other avenues of therapies for Michelle that could possibly slow the disease maybe at least to buy her enough time until a real breakthrough cure might be available. When I researched what was going on at the cellular level I was convinced that we could approach therapy from a deficiency standpoint, since efforts to reduce substrate of cholesterol did not prove beneficial. A deficiency, I mean that cholesterol was not getting where it needed to go to feedback to the ldl receptor to shut down the excess flow of cholesterol into the cell. I talked about the idea of a feedback therapy, possibly supplementing with hormones (a downstream metabolic product of cholesterol) to Dr. ORY and Dr. Pentchev at my first family conference in New Orleans. They listened and agreed it was a good theory. In the next year Dr. Ory did research showing that a synthetic cholesterol byproduct decreased lipid storage material in the cell. At the next conference I talked to Dr. Liscum about the successful results of his research, but she felt this would not have any practical benefit. The next year Dr. Ory did the same research in an NPC mouse model and showed dramatic clinical benefits. So at the next conference, I wondered why this wasn’t getting any attention and I asked Dr. Liscum about it and she became basically mute on the subject. Is it possible we could treat our kids with byproducts of cholesterol and get dramatic disease delay? I don’t remember offhand if Dr. Ory’s research was done through a chow diet or through intravenous . It was only after Dr. Ory’s breakthrough research that this disease is now being viewed as one of deficiency as well as storage. Now the research is going in a direction of getting a drug that would also get the cell to signal a feedback. I just wonder if it isn’t possible to use natural methods to get better, quicker, and healthier results.

    Around the same time I found Dr. Cynthia Mellon’s research on Allopregnanolone and DHEA deficiency in mice. When I directed this research to the foundations Scientific Advisory chair, I received a reply that this research did not pan out. I insisted that they must go back and review this research because it did indeed pan out. I believe they did recheck the research and Dr. Mellon’s research only then got the recognition it deserved. As the mice aged the deficiency became worse. Mellon added allo in an NPC trial and got dramatic delays in deficits. I asked Dr. Mellon at one of the family conferences why we haven’t tried DHEA and I think she explained that mice have very different proportional levels from humans. I think DHEA should be explored ASAP since we could remedy a possible deficiency immediately. Has anyone explored a deficiency? My Dr. would only look at estrogen and progesterone–it seemed o.k. but we weren’t sure about where Michelle was in her monthly cycle so I don’t know if the results meant anything. I thought possibly supplementing with hormones would be a good strategy. I first tried Pregnanolone (the “mother” hormone that metabolizes into most of the others. This seemed to have a negative effect on Michelle although I only tried it 2 days. Later I came to read that NPC disease makes excessive amounts of progesterone, so I knew that Pregnanolone could convert to progesterone and the metabolic block was somewhere below progesterone. I found DHEA was available and it would not convert to progesterone. I tried DHEA on Michelle and she became more clear headed and energetic.
    Another note on the Mellon research is they tried an antidepressant that is known to raise allopregnanolone levels. This did not work. I feel this is all the more reason to try and go as natural a route as possible. I believe as parents of this organization that we need to push research in a more natural and accessible way then to look for drugs that can’t do the job as well and come with side effects. What killed me about the latest Natural History study is they are looking for clinical markers of this disease and they didn’t even bother to measure DHEA or allopregnanolone levels! When are we going to do this!!! If it was found that NPC children are deficient in allopregnanolone couldn’t we as an organization lobby in some way to have access to this natural hormone (that is available to research scientists) to bring levels up to normal?

    My latest interest is about how calcium is processed, and according to an article on pubmed how getting calcium to get through the cell with a calcium agonist also corrected the lipid problem. Calcium seems to currently flood the cell much like lipids and I believe they are processed together much like one carries another. A block for one ends up being a block for the other. Maybe if we can find a way around the lipid block by manipulating a calcium push like they demonstrated with A2187 they could effect a cure. On the down side pushing even more calcium into the cell would likely kill the cell. I’d like to see the possibilities here really explored some more. In response to this research I added supplemental Zinc to Michelle’s diet as a competitive inhibitor to prevent excess Calcium flooding the cell. I thought Michelle showed benefit in that she became less restless and her hands became more open and less rigid.

    Even before DHEA, I was the first to use CoQ10 and I reported her positive changes. I got a lot of cynical remarks that the disease fluctuates and there are going to be good days and bad days, but believe me she had months of great days! A side effect problem that came up was she started to have schizophrenic like episodes. Shortly after I started her on DHEA her schizophrenic episodes disapeared. When we took Michelle off CoQ10 and DHEA for the drug trial she became much more easily tired ie. on CoQ she can walk to our park and off CoQ she can barely make it down the driveway. This has been a consistent difference over the last 7 years. Phil Marella through Dana’s Angels Research (DART) sponsored a mouse trial with CoQ10 but unfortunately Dr Patterson told me it did not increase their longevity. I don’t know if the results would be any different but I believed they used CoQ9 in the mouse study because this is what is natural to them and not CoQ10. Does anyone else know if this is for sure what they used?

  3. Lee King says:

    Our son Lee is 16. He was diagnoses at age 7. He was misdiagnosed at three months with Neonatal Hepititas. At age 5 Lee’s doctor became concerned that he could not walk a straight line or hop on one foot and because his speech was slightly slurred. After two years of testing, Niemann-Pick was diagnosed. Lee’s decline happened gradually -really fast. First year of school, he had to have help going up steps and then he’d walk to class by himself. Second year, I had to walk him to class holding his hand, the third year I had to support him under his shoulder. The forth year he was in a wheel chair and lost much of his speech. His feeding tube was placed that year and he had his first seizure. We tried cholesterol lowering drugs and removed fried foods from his diet until the feeding tube became neccessary. We began him on CoQ10 in the sixth grade. We believe we saw mental and physical improvement for a time. He now goes to high school half-days. He seems to understand what we say to him and still gives us the thumbs up sign when we ask him. He can speak volumes with his eyes. His gross and fine motor skills are extremely limited. He has been fortunate to not have had an overabundance of seizures. Over his lifespan probably under 50. We give him tegretol and believe it was exactly the right choice.
    His grandfather and great grandfather have a history of heart failure. His mother has high cholesterol.
    Hope this helps.
    Melissa King

  4. jenelle spencer says:

    Hi, my name is Jenelle and I have 4 children- 18, 16, 14 and 11. My 14 year old son has been diagnosed with NPC. The disease has slowly been progressing over all these years but Jesse is still doing quite well. He remains ambulant but does stumble and is unbalanced at times. Jesse is a very social teenager and loves to talk and make new friends. Jesse has no insight into his condition and never enquires why he cant do things he once has. He is very happy and continually talks. Cognitvely he is doing well even though his writing skills and reading skills are quite poor.I am very interested in looking towards a cure and joining this action group. Let me know what information I can send to you and what I can do to help..We live in Melbourne Australia

  5. Ghassan Moubarak says:

    Dear Sir/Madam
    Glad to know there are people like you in the world taking the initiative to fight this monster. I have a 6 yrs old daughter who has been diagnosed last year with NP-C. I will send her medical history in another letter. Now I am just writing to say I am happy to join your efforts to fight this disease, though my medical background is zero.
    Good luck to you
    Jason

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