The search for meds to treat cavernous angiomas

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The search for meds to treat cavernous angiomas

Postby Connie Lee » Sat Oct 02, 2010 12:55 am

This was the lead story in our last newsletter - I'm posting it here for anyone who may have joined us since the newsletter was published. The take-home message is that medications are on the way, but we need you to sign up for the registry (http://www.angioma.org/registry) so that we'll have enough people to help when the time comes for trials. Without you, there can be no cure.

And Then There Were Three

In the spring of 2009, we were very excited to announce the first published research indicating that a non-surgical treatment for cavernous angiomas may be on the horizon (Whitehead, 2009). Dr. Kevin Whitehead and his team at the University of Utah demonstrated that statin medications, specifically simvastatin, were effective in reducing the leakiness of blood vessels in mice that were bred to have the Ccm2 genetic mutation. Statin medications are already in widespread use to lower cholesterol. Right now, the group in Utah is performing a retrospective study using records from thousands of patients treated for cavernous angiomas in Utah. They are hoping to gather enough supporting information to apply for a major grant to perform a clinical drug trial to demonstrate the effectiveness of statin drugs in human cavernous angioma patients.

This spring, Rebecca Stockton, Dr. Mark Ginsburg and the group at University of California at San Diego published research identifying another medication, generically known as fasudil, as being effective at reducing leaky blood vessels in mice bred with the Ccm1 genetic mutation (Stockton, 2010). Fasudil is a “Rho Kinase inhibitor” and works on cavernous angiomas in a way that is similar to statins. Fasudil has been used in Japan for more than 15 years to treat cerebral vasospasm. Currently, in the US, it is undergoing clinical trials to gain approval by the FDA to be used in the treatment of pulmonary hypertension and other conditions. At this time, the UCSD group is working with Dr. Issam Awad’s group at the University of Chicago to continue to explore the effects of fasudil. There is not yet a clinical drug trial specifically for the treatment for cavernous angioma.

Finally, in July, Joycelyn Wüstehube in Dr. Andreas Fischer’s lab in Heidelberg University, in Mannheim, Germany published a paper documenting that yet another medication, sorafenib, potentially is effective in treating cavernous angioma (Wüstehube, 2010). Sorafenib was shown to shrink cavernous angiomas in mice bred without immune systems that had received a transplant of human CCM1-mutated endothelial cells. Sorafenib works by blocking the growth of new blood vessels, and it has been used to slow the spread of cancer in individuals with advanced primary kidney cancer and with advanced primary liver cancer. A downside of sorafenib is its price; for example, it has been disallowed for use as a treatment for liver cancer by the United Kingdom National Health Service because treatment can cost more than $4500 USD/month. The identification of sorafenib, however, has opened the door to a different class of medications that can be explored.

The research above focused on the CCM1 and CCM2 genetic mutations. Does this mean that statins, fasudil and sorafenib are specific to these mutations, or will they work for all types of cavernous angiomas? This is a question without a solid answer. All of the CCM proteins (CCM1, CCM2, and CCM3) that cause the hereditary form of the illness have been shown to be part of the same system. Sporadic cavernous angioma lesions are indistinguishable from those in the inherited forms of the illness. It may be that a medication that works for CCM1 could also work for CCM2, CCM3 and sporadic cases. However, the more researchers learn about the function of the CCM proteins, the more they find that each has additional unique functions. How these functions affect the illness remains unknown. Additionally, what is not known is whether these effects would generalize from mice to humans. It would be hard to exaggerate the amount of scientific progress in the research described in the three studies above and the work that led up to them (Borikova, Dibble, 2010). The next step, which is equally important, is to refine knowledge about the disease biology and move toward clinical trials. We are not there yet, but it is coming.

What does this progress mean for us today? Right now, there is no reason to run out to get a prescription for any of these medications. We do not know whether they truly are helpful or harmful to humans with cavernous angiomas. If they are helpful, we don’t know that this is the case for everyone with the illness or just those with specific mutations. We also do not have information on what dosages might be required to have an effect.

What it does mean is that growing the size of the Angioma Alliance International Patient Registry is of critical importance. If we would like to see medication research in humans happen as quickly as possible, we need to provide researchers with an already organized group that has offered to participate in research studies. Since the three drugs identified so far are on the market and already proved safe and effective for other conditions, if they work for cavernous angiomas as well, we could see a much shorter time to FDA approved use if we can pull our resources together than might otherwise be the case. To participate in the Angioma Alliance International Patient Registry, visit http://www.angioma.org/registry.
Connie Lee
President and CEO, Angioma Alliance
17-year-old daughter with CCM3 mutation who has had 4 brain surgeries, T2-L3 spinal fusion
To support Angioma Alliance, visit http://www.Angioma.org/Donate.
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Re: The search for meds to treat cavernous angiomas

Postby leftparitallobe » Wed Jan 26, 2011 9:04 pm

In 08 at NIH.gov in Maryland found a 6-7mm CCM in my husband's brain deep in bottom left parital lobe, surgery not possible. His genes were checked through Wisconsin Genetics one of the few places we were told that checks for this mutation that said they believe it to be sporatic not familar. It is scary we live each day with thankfulness for what we do have till a cure comes. Our prayers go out to everybody dealing with this. It is difficult to take in and know there is nothing in this great world that can help. We need something, studies or ideas to take to the neuro to see if any of these are any good. Has anybody heard of foods and/ or supplement studies to help stregthen the vein/artery walls or prevent more CCM's or bursting? We found a study on www.clinicaltrials.gov being done at San Francisco U on medicines it was either doxycycline or dioxycycline that is used in some way. I have heard of supplements that can stregthen veins/arteries like Vitamin C, Pycnogenol, horse chestnut seed extract which we will be asking the neuro about but would love more to share with the neuro. Thanks
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Re: The search for meds to treat cavernous angiomas

Postby Elizabeth » Thu Jan 27, 2011 7:29 am

Thanks Connie for all you do!!! Hopefully there will someday be a cure without surgery.
Diagnosed September '09 with one CM centered in the right insular cortex/basal ganglia. Saw many, many doctors and had surgery 12/10/10 with Dr. Spetzler. I am thrilled to have this bleeding thing out of my head even though I suffered a stroke during surgery. Have had/ continue to make an amazing recovery. http://www.thankfulforeveryday.blogspot.com
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Re: The search for meds to treat cavernous angiomas

Postby Connie Lee » Thu Jan 27, 2011 2:58 pm

The doxycycline study is actually more about AVM's than cavernous angiomas. Having spoken with researchers involved in the study, the hypothesis is that doxycycline would help people with AVMs, but not people with cavernous angiomas.
Connie Lee
President and CEO, Angioma Alliance
17-year-old daughter with CCM3 mutation who has had 4 brain surgeries, T2-L3 spinal fusion
To support Angioma Alliance, visit http://www.Angioma.org/Donate.
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Re: The search for meds to treat cavernous angiomas

Postby leftparitallobe » Mon Jan 31, 2011 7:53 pm

Why do they think it would help AVMs but not CCMs? Just the luck but interesting that it could help a large bleed but not small ones. I wish there was more out there about alternative meds/vitamins etc. that can do simple things like stregthen vascular walls and things. But the vitamin C and stuff looks like an interesting thing to atleast open up conversation about with the neurologist.
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Re: The search for meds to treat cavernous angiomas

Postby Elizabeth » Fri May 27, 2011 6:27 pm

Any updates on drug trials? I used to work for Abbott and was thinking about asking them to help. If they already make a drug that might be helpful, I'm sure they'de be interested in increasing pt. usage by expanding the patient population for their drug. Are any of the testing cm drugs from Abbott?
Diagnosed September '09 with one CM centered in the right insular cortex/basal ganglia. Saw many, many doctors and had surgery 12/10/10 with Dr. Spetzler. I am thrilled to have this bleeding thing out of my head even though I suffered a stroke during surgery. Have had/ continue to make an amazing recovery. http://www.thankfulforeveryday.blogspot.com
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Re: The search for meds to treat cavernous angiomas

Postby Mitch » Wed Sep 12, 2012 3:22 pm

I have heard of new tests to cure cancer with antipodies, that destroy the tumor in your body, maybe the same is possible with cavernous angioma, then a surgery wouldn't be necessary.
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Re: The search for meds to treat cavernous angiomas

Postby vandy » Thu Sep 13, 2012 11:32 am

Hi Mitch,

Would it be possible for you to add to your post the sources of information you are using? The articles you read and the web links to them; this would make it easier for people to get the same information, and read up on it.

As for this being a possible treatment for cavernous angioma, I would have my doubts. Based on just the mere biology, a cancer tumour is different from regular tissue and therefore it can be distinguished as such. In vascular malformations, you are dealing with just a bit more regular tissue in the same location; it is not cancerous and therefore can't be distinguished from other regular tissue. Just based on this simple comparison I would say that it would be harder to treat cavernous angioma with this type of treatment.

Henk :ugeek:
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Re: The search for meds to treat cavernous angiomas

Postby kirkmc » Thu Sep 13, 2012 2:42 pm

Mitch wrote:I have heard of new tests to cure cancer with antipodies, that destroy the tumor in your body, maybe the same is possible with cavernous angioma, then a surgery wouldn't be necessary.


I don't know much about what you're describing, but a CA is very different from a cancerous tumor. It's not a malignant growth that's out of control, and in many cases doesn't grow much or at all. As a malformation, it's not even "foreign" tissue, just blood vessels that are all screwed up.
Two brainstem CAs in the pons. Big Bleed in July 2005, previous, undiagnosed bleeds in 1982 and 1987, and several smaller bleeds in the past few years. I live in a town in the French Alps. http://www.mcelhearn.com
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Re: The search for meds to treat cavernous angiomas

Postby vandy » Wed Sep 19, 2012 5:42 pm

Kirk Wrote:
it's not even "foreign" tissue, just blood vessels that are all screwed up


I love that description - all screwed up.
At least we have scientific evidence that we are screwed up :lol: :lol:

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