What are SARMs?

I read this post from Tom Edward on the KD - Canada Facebook page: 

I heard back from Dr. Fischbeck last night. So SARMS are under active development for SBMA. We studied ASC- JM 17 and a lab in Tawain just received FDA approval to initiate a clinical trial. Paul Taylor's lab at St. Jude's did a study in mice and they were shown to be effective and at least 2 companies are interested in developing the drug. Diane Merry a researcher at Thomas Jefferson in Philadelphia is also working in the lab with other SARMS for SBMA. So it is having some positive results in the mice now let's hope it could translate into us humans.

So, I looked up SARMs and this is what I found...

Selective androgen receptor modulators or SARMs ...

are a novel class of androgen receptor ligands. They are intended to have the same kind of effects as androgenic drugs but be much more selective in their action, allowing them to be used for more uses than the relatively limited legitimate uses of anabolic steroids.

They are intended to have the same kind of effects as androgenic drugs but be much more selective in their action,[1] allowing them to be used for more uses than the relatively limited legitimate uses of anabolic steroids.

Ref:  Wikipedia

Current Uses: Hypogonadism; Osteopenia; Osteoporosis; Sarcopenia; Cachexia

SARMs are not approved by the Food and Drug Administration (FDA) for human use, They are illegally marketed and sold as dietary supplements, and they are banned in all professional and college sports. “SARMs are synthetic drugs that have negative effects similar to those of anabolic steroids, [Google Search of SARMs]

Federal Funding for Research Update

Good news! Thanks to many of you who contacted their Congressional Representatives, federal funding for research was increased through FY-2017.

The MDA Advocacy newsletter reported the following:

Congress boosts federal funding for research

This month we thank Congress for including a boost to research funding in the recently passed omnibus spending package that funds the federal government through the end of fiscal year 2017.  The budget package includes a $2 billion (6% increase) for the National Institutes of Health (NIH).  MDA appreciates every lawmaker that supports increased funding for biomedical research and thanks to all advocates who urged their members of Congress to help ensure that NIH received this critical funding increase.  As budgeting for fiscal year 2018 moves forward, we will continue to call on Congress to keep up the momentum by committing to robust and consistent funding increases to NIH in this and future budgets.  With four new drug approvals for neuromuscular disorders in the past year and with a robust drug development pipeline, we must continue the push to make NIH funding and biomedical research an ongoing bipartisan Congressional priority.

Another call for action - NIH Budget Cuts

Take action to prevent cuts to federal research funding

We need your help to urge Congress to reject proposed cuts to National Institutes of Health (NIH) research funding. Support for NIH is critical as it is the largest funding source of biomedical research in the United States, and why ensuring adequate funding for NIH is one of MDA's policy priorities. While research funding from organizations like MDA - which has invested more than $1 billion in research - is significant and is moving the needle, robust federal funding is essential to finding treatments and cures. Congress has come together in a bipartisan effort to support NIH funding in recent years, and it is up to all advocates to ensure that the bipartisan support continues. NIH fuding was increased in fiscal year (FY) 2016, and increases were proposed for FY17, though a final budget agreement for FY17 has not yet been enacted. It is a concern that there is no final budget in place for the current fiscal year, but of greater concern are the NIH budget cuts outlined in the President's budget blueprint (a $5.8 billion cut to NIH equivalent to 18% of the overall budget).

We must work together to ensure that research funding is not cut, and that NIH support continues to grow through strong bipartisan support in Congress. To deliver this message in person, researchers from leading institutions around the country visited Capitol Hill on March 22 in conjunction with MDA's 2017 Scientific Conference to urge Congress to reject any proposed funding cuts and to instead enact sustained and robust funding increases for the National Institutes of Health (NIH).

Now it is your turn to amplify this message. Please take a moment today to urge your members of Congress to maintain the bipartisan support for research and to reject any proposed cuts that would harm quest for the development of treatments and cures. 

We need to be heard! 

Years ago, I ignored these "calls for action" believing that they really didn't do any good. I am now an advocate of this approach. I now know my congressional representative's staff, an occasionally my representative, reads these emails. Even better, I receive a response and often a follow-up email explaining what happened and why. Thank you for your consideration. Please click on the "TAKE ACTION" above.

Kennedy’s Disease BVS857 Trial

Many of us have been patiently awaiting the published report on the recently concluded Kennedy’s Disease BVS857 trial at NIH. Two of the attendees provided the following information on the trial. Once the actual paper is published, I’ll provide a link to it

.

Dr. Kenneth Fischbeck of the NIH gave a report on this trial at the KDA Conference in San Diego last week. He stated that while there were some modest positive results it did not meet expectations. In part that may have been because they only conducted the trial for 12 weeks and the nature of the drug and its effect would suggest slowly increasing benefits over an extended time frame.

The compound was intended to improve insulin sensitivity in people with KD and boost the anabolic effects of insulin and IGF1. Unfortunately, it also stimulated an immune response in some patients taking it producing anti-bodies that not only attacked the drug but also attacked the person's own insulin or IGF1. Fortunately for those affected after discontinuing the drug the immune response faded. Novartis aborted their trial plans and terminated further investigation of the compound.

The following is a quote from Dr. Fischbeck. “We too are disappointed that the Novartis agent was not more effective, but we are optimistic that the results from this trial will help in developing a treatment that really works for Kennedy’s disease. The study gave us information about muscle imaging and clinical outcome measures that will improve the design of future trials, and it helped to set up a network of trial sites that will allow clinical studies to be done more efficiently. Also, it gave an indication in the effect on muscle size that other drugs targeting the same pathway might be effective.”

The BVS857 Trial is Completed

Most of us living with Kennedy's Disease are anxiously awaiting news of the BVS857 trial. If you can't remember what the trial is, follow this link:  Safety, Tolerability, and Efficacy of BVS857 in Patients With Spinal and Bulbar Muscular Atrophy

I also wrote about it in earlier blogs:

• Information on the NIH Clinical Trial
• Update on Clinical Trial  - Link to Video

 Yesterday I reached out to Dr. Fischbeck at NIH. He was kind enough to respond to my inquiry. I realize it isn't anything definitive, but it means the results will be published soon.  FINGERS CROSSED

Thanks for the message, Bruce. The active phase of the BVS857 trial has ended, and the results are being analyzed. We currently plan to present the findings at the KDA meeting in the fall, and will likely be able to get some word out earlier, hopefully in the next month or two.

It’s OK to let the others know.

Kurt

Kennedy's Disease Research; Future possibilities in

Last Saturday, Ed Meyertholen, the KDA's resident biology professor, was the KDA's Forum guest. As always, Ed provides information in a manner that is understandable to almost any audience.

Below are some of Ed Meyertholen’s comments and answers to specific questions concerning CRISPR and iRNA research. To read the entire forum discussion, follow this link: http://www.kennedysdisease.org/index.php/provide-support/chat-room-transcripts/2016-chat-room-transcripts/627-2016-february-06 .

“I am not a CRISPR expert, but the technique has been quickly (in the science view of quickly - several years) improving and it is expected that it will continue to do so. I do not think we will see this in humans for a while (years). 

In KD, I can imagine there may be issues on specificity - what cells to send CRISPR to, nerve cells or muscle (or both) and then one has to develop the procedures to specify the cells. The CRISPR work is very new and I do not know if anyone is working on it in Kennedy’s Disease. I suspect that someone will be soon. Nonetheless, I think that it has great possibilities - and I am usually not too optimistic. 

What happens is that they use a virus that normally attacks a specific cell type (like muscle), remove the DNA from the virus and replace it with the DNA needed to get CRISRP to work. The virus with the CRISPR DNA in injected into blood, goes to the muscle cells and instead of injecting viral (bad) DNA, injects the CRISPR DNA. The CRISPR DNA then lets the muscle cells make the CRISPR proteins which then should (and in the mouse, did) alter the DNA in those cells only. DNA in other than muscle cells is not affected. 

Kennedy’s Disease may give rise to other issues - the androgen receptor (the mutated protein) is made in many cells and may have effects (sexual issues, gynomatica (sp)), so we might want to alter the gene in other cells as well. It has great possibilities but it is not ready for prime time yet. This is the CRISPR paper:  http://www.ncbi.nlm.nih.gov/pubmed/26721684.

There was another paper from NIH (Kurt's lab) where they used iRNA to block the synthesis of the mutant androgen receptor and found that the mice got better. This is similar to work from LaSpada and from Lieberman that had been published a few years ago. These were done in conjunction with drug companies and I would not be surprised if there would be a clinical trial (I think that there is one starting using the same technique in Huntington's Disease) now. The other techniques with iRNA or ISO's are much closer to clinical use. If I remember correctly getting to nerve cells requires getting past the blood-brain barrier issue(s). Kurt's paper is here - http://www.ncbi.nlm.nih.gov/pubmed/26755334 .”

Photo:  http://www.science.ca/images/altman_rnase.jpg