Kennedy's Disease / Spinal and Bulbar Muscular Atrophy

General Discussion
#1

kennedysdisease.org/about.html

The androgen receptor is a protein that lives inside the nerve cell. Lots of cells have the androgen receptor protein, but motor neurons have more than most. The androgen receptor sits around waiting for testosterone to come and bind to it. The binding of testosterone to androgen receptor somehow kicks off the disease. Since men have much higher levels of testosterone, they are affected by the disease

Briefly, KD is caused by a genetic mutation to the gene that codes for the Androgen Receptor (AR) protein. This protein mediates all the actions of the androgen hormones testosterone and dihydrotestosterone, DHT. In the cells of normal males, the AR is found in the cytoplasm of the cell. Upon the addition of an androgen hormone (either testosterone or DHT), the hormone binds to the AR and the hormone/AR complex travels to the nucleus of the cell where it initiates the masculine changes that are associated with the presence of androgens (beard growth, for example). If there is no androgen present, then the AR never enters the nucleus and there are no changes – this is essentially what occurs in females. Since women do not possess androgens, the AR does nothing in cells and there are no masculine effects. The AR in the nucleus is ultimately destroyed by a cell structure known as the proteasome. In individuals with KD, the cell is unable to completely destroy the AR that enters the nucleus - but it can destroy the AR that does not enter the nucleus and this inadequate digestion apparently results in the production of a fragment of the mutant AR that is toxic to the cells – thus the cells die and this leads to the formation of the symptoms of KD. This appears to explain why women carriers do not show major symptoms. Since the levels of androgens in women are low, the mutant AR does not enter the nucleus and the cell does not create the toxic fragment.

#2

What’s your point? And why is this posted in the “Theories” section?

#3

A $25,000 grant was awarded to Maria Pennuto, Ph.D. from the National Institute of Health. Dr. Pennuto has spent the past few years investigating the molecular switches on the AR that are involved in the movement of the AR into the nucleus upon addition of hormone. She has discovered that certain chemical changes to the AR seem to reduce the ability of the AR to bind to hormone and thus not enter the nucleus (and cause KD!!). She has discovered that the exposure of cells to a substance known as IGF-1 can induce these chemical changes to occur to the mutant AR and thus prevent the movement of the AR to the nucleus. Thus, the addition of IGF-1 to a cell with mutant AR appears to prevent the formation of the toxic fragment and thus the cell stays alive. Dr. Pennuto will continue this work by determining if any other chemical changes to the AR may alter its movement to the nucleus and she will also determine if IGF-1 prevents the formation of KD symptoms in a KD mice model (up to this time, the effect of IGF-1 has only been shown to work in cell cultures. This work could lead to new therapies for KD.

kennedysdisease.org/research.html

#4

i was getting to that. I have been looking up CAG repeats and stuff. basically this disease is something that doesnt rear its head until later in life. from what i have been reading it starts off/worsens when testosterone hits the androgen receptors. usually shows up mid 30s-40s. what if we have this disease and we kick started by suppressing the 5AR and building up too much testosterone. its a horrible possiblity but one none the less that would help explain our symptoms and it seems easy enough to test for to confirm or rule out.

further, there are researchers for this right now that are working on studying AR mutations and perhaps we could reach out to them regarding our situation!?

also if i am reading this right it looks like she was able to curb off the effects of the mutation with IGF-1

isnt that the point of the “theories” section?

#5

I was worried I was getting Kennedys or some other androgen receptor disease at the beginning with my muscle loss and shrinkage, neuro seemed to rule it out. I thought you’d seen a neuro?

#6

How did he rule this out? A nerve conduction test?

#7

I don’t think so, he made me walk about and did that thing where they hit your knee for a reflex. He probably did a couple of other things I’ve forgotten about. He was cool and believed my story but said it would ‘flush out of my system’ then referred me on to an endo. No EMG testing or whatever it was that mew got.

#8

I did see a Neuro but who knows what she is thinking

#9

soemthing else of note. i remember that JN had gotten much better with HGH which increases IGF-1

#10

Its your theory, so prove it right or wrong or youre wasting everyones time

#11

haha ordering right now buddy its open in the other tab right now - by the way im hoping for the love of GOD that this ISNT what we have this would be aweful. a disease that makes your AR not work and the more testosterone you give it the worse it gets

#12

thank you for doing that wontgiveup

#13

no worries! whats another hundred bucks at this point

#14

mda.org/publications/Quest/e … /sbma.html

Mice with an SBMA-like disease benefited from extra IGF1 genes in their muscle fibers

Note: “LIKE-disease” even if we dont have this disease… this wasnt the exact thing either but IGF1 helped

#15

Nice one bud, :smiley:

#16

Got tested for this this morning via an emg and nerve conduction test - which let me tell you is not pleasant (they stick needles in your muscles and move them around) and it was 100 percent normal.

#17

Have you had any muscle loss/twitches?

#18

Guys, do you know dutasteride is Kennedy Disease patients miracle drug?

Maybe we suffer something similar, in that andorgens/ dht are harmful for us ever since they returned when dropping finasteride

#19

Post links to info regarding this to elaborate further please.

#20

kennedysdisease.blogspot.com/2011/07/dutasteride-update-five-months.html

kennedysdisease.blogspot.com/2011/09/dutasteride-and-asc-j9-updates.html

ncbi.nlm.nih.gov/pubmed/21216197

Kennedy’s disease is completely different to PFS obviously, but i think it’s interesting because it is something to do with the androgen receptor and DHT is not good for these guys. Considering so many of us ‘crashed’ when DHT probably came flooding back, you never know, maybe it is harmful for us too? i am not trying to put forward a serious theory here, simply writing down some thoughts. I am most interested in there use of dutasteride.

I think Blase is onto something when he talks about DHT being pro inflammatory in some cases. The ‘crash’ event makes me think we had/ are having a bad reaction to DHT since we stopped suppressing it by 70% using finasteride.

“Spinal and bulbar muscular atrophy (SBMA) or Kennedy’s disease is a slowly progressive,
X-linked motor neuron disease for which there is currently no treatment. It is caused by a
mutation in the androgen receptor that results in a polyglutamine repeat expansion. Recent
animal studies have demonstrated that decreasing endogenous androgen levels leads to
functional improvement and increased survival. Studies have also shown that high levels of
5 alpha-reductase, the enzyme that converts testosterone to the more potent
dihydrotestosterone (DHT), are present in the ventral spinal cord, while low levels of this
enzyme are found within skeletal muscle. Thus, by selectively decreasing levels of DHT with
dutasteride, a 5 alpha-reductase inhibitor, it is hypothesized that there will be a
selective protection of motor neurons, without the adverse effects of reducing the anabolic
effects of androgen on muscle.”