A long day

I don't have the Exon skipping and combination therapy information I promised, I'm sorry to say. And I won't say I’ll have it tomorrow because I’ve already been wrong. It is six in the morning and I am just getting home from work. And I left people still working at the lab …

If I am busy (and I am ☺) then our Principal Investigators preparing for our upcoming research review are even busier.

The March 8th meeting is a major undertaking, with the Cooperative International Neuromuscular Research Group review being the main focus. Additionally, there will be four scientific advisory committee meetings.

Besides the international doctors, clinical evaluators and therapists from the clinical trials group, attendees will include Principal Investigators for the DC Wellstone Center and the Translational Research in Duchenne Dystrophy Program, Program Officers from NIH and DoD, and representatives from Biopharma and muscular dystrophy foundations.

Then, there is my group: local parents and older kids with muscular dystrophy. They will be joining the docs and scientists Saturday evening for the dinner and the 20th Anniversary celebration of the discovery of dystrophin.

The honorees will include: Lou Kunkel and his Boston team, who discovered the dystrophin gene; Anthony Monaco, Eric Hoffman, and Michel Koenig. And, of course, MDA who funded the research and made It happen.

There is one guy who will not be there that everyone should know. His name was Bruce Bryer. Thanks to Annie Kennedy and Phil Ivory from MDA, for sharing Bruce's story with me.

Bruce had duchenne dystrophy. Born in 1966, he was missing a large chunk of his X chromosome. His blood provided invaluable ‘genetic information' to the Kunkel group and aided in a big way, their quest to find the dystrophin gene. He died Christmas night 1983, three years before the gene was identified.

Now, twenty years later, with infusions of technology, money and time, we are where we hoped this discovery would take us, contemplating a treatment for muscular dystrophy.

Our celebration is focused on the Kunkel team but, in this luminous moment, we remember Bruce Bryer. We remember, too, all of our boys who have already given much. We remember, and we keep working.

Multiple Exon Skipping - Is it effective?

Yesterday, I asked Terry Partridge, via email, if multiple exons could be skipped effectively. The question had been raised.

Terry Partridge, for those of you who don't know him, is an amazing scientist, working at Children's National Medical Center, GenMed. Among his projects, is Regenerative Failure in DMD, under the Wellstone Center. He is an expert in the field of exon skipping - and he has that funny, dry, British sense of Humor!

Below is his response.

The argument is based on the idea that the effectiveness of each AON is independent of the effectiveness of all of the others, whereas the evidence is that they are linked.

So far as we can tell their effectiveness is limited by whether or not they get into individual muscle fibres and this in turn seems to reflect the status of the fibre at the time the AONs are given. So the argument in favour of cocktails is that all 10 AONs will get into those fibres that are slightly leaky and that it is this access that is the limiting factor on their individual effectiveness not the ability to find their target sites once they are in.

The evidence supporting this view is that we have to get three AONs into the dog to get good skipping there and that this seems to work well in practice. The overall efficiency is chiefly a reflection of the proportion of fibres that produce dystrophin and only to a minor extent of the amount of dystrophin that the positive ones produce.

Hope this helps.

Terry
--
Terence A. Partridge Ph.D. FMedSci,
Center for Genetic Medicine Research,
Children’s National Medical Center,
Washington DC 20010

Please come to our "Weekend in South American" at Children's in DC!

This link to a previous post gives you all the details!
Hope to see you there,
GenMed Lab Mom

Non hormonal steroids - possible clinical trials to be discussed at the March 8th meeting

I spoke with Kanneboyina Nagaraju, DVM, PhD, yesterday about nonhormonal steroids and clinical trials being discussed at the March 8th meeting. Raju, as we call him, has the second largest lab at GenMed and his forte is translational research and working with the mdx mouse, the mouse model for duchenne dystrophy.

He has been testing a steroid derivative of prednisone, tweaking it in order to lessen the side effects of prednisone, like behavior changes, cataracts, stunted growth, brittle bones, etc, while maximizing the potency of the good stuff in prednisone, essentially making a drug that is nonhormonal.

They have had great success at the bench and with the mdx mouse. After completion of toxicology studies they would like to propose a clinical trial for boys with duchenne.

CINRG, is a cooperative clinical trials network and different centers can chose to participate in trials or even start their own trials using the infrastructure the coordinating center (us) has in place. Nonhormonal steroids is just one of several clinical trials that will be proposed at the meeting.

Terry Partridge is writing up a little something on possible morpholino clinical trials and I'll post something, hopefully this weekend, on the combination therapy trials being discussed at the March 8th meeting. I'm waiting for input from one of the docs out on maternity leave.

Congratulations Toshifumi and Rika - and a look at upcoming posts

Congratulations Toshi and Rika

A quick post to share Toshi and Rika's wedding moment. Just look at Rika's gorgeous dress and artful bouquet - and Toshi, the dashing bridegroom. Ah, newlyweds!

May your life together be happy, prosperous and full of joy.

*************************

Of course, Toshifumi will be back in time to attend the March 8th clinical trail and translational research program update and 20th anniversary celebration.

Coming up this week on the GenMed Lab Mom blog - a quick look at possible clinical trials being discussed at the meeting:

Exon skipping

Combination Therapy

Non-hormonal Steroids

Thanks visitors and guest blogger, Tina Carson

Thanks for the blog visits from all over the world this week, especially from Istanbul, Turkey; Melborne, Australia; Mumbai and Chennai, India; Karachi, Pakistan; Auckland, New Zealand; and Dededo, Guam.

Also hello to the many, many friends in the US and Canada, with the hot spots being California, Texas, DC, Maryland, plus Cambridge and Ingersol, Canada.

Thanks for the visits!

Today's guest blogger is Tina Carson, who graciously consented to share her blog about one of my favorite people, my boss, Eric Hoffman :).

Tina's son, Mark, has duchenne muscular dystrophy. Tina, husband Dan, and Mark and his big sister (see below) live in Harve de Grace, Maryland where they had a hughly successful fundraiser last May called "Son Rise" for muscular dystrophy research. Thank you Tina for your article and your research support.

FRIDAY, FEBRUARY 15, 2008 09:25 AM, CST

HOPE FOR MARK, JAMES, ALEX, JOHN, A.J., JOEY, DREW, ADAM, KEVIN, PETEY, ........ and so many more ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ For some time, I've had this picture of Dr. Eric Hoffman and Mark displayed on Mark's website. I don't think I ever properly introduced our hero, Dr. Hoffman, to the viewers on Mark's website. Duchenne is caused by flaws on a single gene called dystrophin, which was first identified by Dr. Eric Hoffman 20 years ago when he was a post- graduate researcher at Harvard. In 1999, Dr. Hoffman moved to Washington, DC to establish the Research Center for Genetic Medicine Research at Children's National Medical Center (CNMC). Today, Dr. Hoffman commands one of the largest and certainly the most aggressive muscle research shops in the world at CNMC here in Washington, DC. He is the Center Director for the Wellstone Muscular Dystrophy Center, one of six NIH-designated and funded muscle disease centers in the United States. As the FED's scientific advisor and the founder of the world's only human clinical trials network for MD, he has always directed us to ( and ultimately is coordinating) the most aggressive clinical research in the world. There are a alot of components to it, but the large majority of our attention and resources recently have been devoted to the clinical translation of "exon-skipping" therapies. We have already proven that we can dramatically slow the progression of DMD using this technique in three of the largest naturally-occurring animal models of DMD- dogs--via our collaborators in Tokyo. On December 27, the New England Journal of Medicine published an exciting paper by Dutch scientist ( whom we've also supported) demonstrating how this therapy offers much promise and hope to so many boys with Duchennes. This is big news, exciting stuff. We may be able to treat boys with Duchenne MD using exon skipping therapies in our own backyard. No need to travel to the UK or to the Netherlands. For the first time in four years, I can rest my head on my pillow at night knowing there is a real possibility of having hope for Mark. The sharp stabbing pain I have felt in my heart for years is slowly starting to dull. And, spending the last four years raising close to $400,000 in donations from our community for research will now help so many boys. I can honestly say today, that I am the most grateful mom in the world! Truly, I am. Dan and I owe it all to Joel Wood, Dr. Eric Hoffman, our families, and to our community. Thank you, Tina

Lab Art - an occasional posting

This beautiful lab art was provided by Pilar Martinez of the Dutch Neurofederation. Thanks Javad Nazarian for giving it to me to post. This is ORF (green), bungarotoxin (red) and SV2+ Neurofilament (blue) (I don't understand it but it's pretty.)

We've got

- so goes the song from the musical of the same name, with everyone dancing around happy as clams because they’ve got Annie. But they don’t – because we do! We’ve got Annie – and we can only say:

“Thank you, MDA!”

Annie Kennedy is the new Vice President of Advocacy for MDA National Headquarters, although she’s not new to Washington or MDA.

She began her career with MDA when she was sixteen years old as a camp volunteer.

I first met Annie ten years ago when she was the MDA patient services coordinator for Washington DC and Virginia. At the time she was organizing young adult activities for the teens in the area

She mentioned to me that she wanted to recruit my son to join the young adult group. ‘Well, good luck with that” was my skeptical response, as she likes to remind me. As you may have guessed, my son, Petey, was only too willing to oblige her and went on to join many young adult activities!

Petey & friends

But kidding aside, the main thing I can tell you about Annie is that her love and support have been like a landmark for local families. She is bright, energetic, and passionate about muscular dystrophy support – whether it’s knocking on doors on Capital Hill, meeting with families or working alongside clinic doctors and researchers.

Annie left the area to head the ALS division at MDA Headquarters two years ago. Now she’s back as Vice President of the newly created MDA Advocacy Team.

As Vice President of Advocacy, her first job is to bring MDA resources to bear on the reauthorization of the MD-Care Act. Annie and MDA are part of the coalition of parents and parent organizations, including Parent Project and the Foundation to Eradicate Duchenne, working together to insure that research funding and progress toward a treatment for MD continues.

thanks, Great Seats.com and American Pain Foundation for the use of their images

Wedding for Toshi & Lindsay's Art

CONGRATULATIONS TOSHIFUMI

Congratulations to our friend and GenMed scientist, Toshifumi Yokota, on his upcoming wedding this Friday, February 15th. He and his bride, Rika, will be married on the tropical island of Guam.

MORPHOLINO RESEARCH

Toshi's work on morpholino in mice and dogs that have duchenne dystrophy shows promising results and we hope to have news about clinical trials in the near future.



In boys with duchenne, the dystrophin gene is defective. This gene is unable to produce the protein dystrophin, in most cases because parts of the gene called exons are deleted or missing. Morpholinos bridge the gap left by the missing exons and creates a good but shorter protein.

EXPERT OPINION ON BIOLOGICAL THERAPY, JUNE 2007

His latest paper, "Potential of oligonucleotide-mediated exon-skipping therapy for Duchenne muscular dystrophy" was published in the Expert Opinion on Biological Therapy in June 2007.

PETEY'S HANDS

The 20th Anniversary of the Discovery of the Dystrophin Gene

On March 8th Louis Kunkel and his original team in Boston (Anthony Monaco, Michel Koenig, and Eric Hoffman), along with other notable scientists in the DMD community will come together for a celebration of the 20th Anniversary of the Discovery of the Dystrophin Gene.

My daughter, Lindsay, was chosen to create a sculpture which will be presented to the honorees at the anniversary celebration dinner.

The figure will be a mold of her brother, Petey's, hands, holding the dystrophin gene. Here is Lindsay 'casting' Petey's hand.

Help Tracy Seckler win $35,000 for muscular dystrophy research

Tracy Seckler is mom to Charley, a cute little guy with adorable curls that I had the pleasure of meeting a couple of years back when he was in Washington, DC for a visit. When Charley was diagnosed with duchenne muscular dystrophy, Tracy, along with her husband, Benjamin, started Charley's Fund to raise money for duchenne research.



Tracy writes a smart and thoughtful blog, found on the Charley's Fund web site. In fact, I happen to think Tracy is one Smart Cookie, which is why I voted for her to win the Smart Cookie Award!

Please vote for Tracy! We have until Friday, February 8 to help Tracy win the Smart Cookie Award and $35,000 for Charley's Fund. $35,000, I might add, that will go to fund research for a treatment for our boys.

Please click below to vote:

Smart Cookie Award



Here is Tracy with the now famous Darius from "Darius Goes West", a documentary about a young man with duchenne dystrophy and his friends on their cross-country trip, which Charley's Fund helped underwrite.

20th Anniversary Celebration

DYSTROPHIN DISCOVERY

Nineteen Eighty Seven was a landmark year for the DMD Community, when an MDA funded scientific team at Harvard discovered the definitive cause of Duchenne Muscular Dystrophy. On March 8th Louis Kunkel and his original team in Boston (Anthony Monaco, Michel Koenig, and Eric Hoffman), along with other notable scientists in the DMD community will come together for a celebration of the 20th Anniversary of the discovery. In recognition of the exciting developments being made in the DMD research and appreciation for the dedicated scientists responsible for these discoveries, MDA and regional families invite you to an evening of gratitude and celebration.

PLEASE JOIN MDA AND REGIONAL FAMILIES

Date: Saturday, March 8th
Time: Reception begins at 5:30 PM
Location:
Children's National Medical Center
5th Floor Research Atrium
111 Michigan Ave NW Washington, DC 20010.


CELEBRATE!

Reception will be followed by dinner and a short program.
There is no charge for admission but places are
highly limited so RSVP early.

RSVP

I will be happy to email or fax you a registration form.
Email at genmedlabmom@gmail.com or
call 202 476 6029.



MDA



If you need additional information, please call Katie McGuire with MDA at
410 494 7072.
We hope to see you on March 8th!

Goodbye Josephine

Wednesday we had a potluck luncheon for Josephine Chen, who is leaving GenMed for greener pastures. Potlucks at GenMed are always amazing because everyone brings dishes from their home countries. I especially love the dishes from India and China. Above are some of the folks who came to wish Josephine good luck at her new job and below, Eric and Josephine make little speeches.



Josephine, our IT guru, resident data warehouse expert, and my friend and confidante, is leaving GenMed for NIH. She will work five minutes from home and, with two small children, that is important.

Besides running our IT department, where integration of complex computer programs and specialized integration needs are the norm, Josephine was largely responsible for creating our Public Expression Profiling Resource (PEPR). PEPR is accessed on-line and warehouses gene expression data (expression data shows how a multitude of genes changes over time and under different circumstances) for thousands of humans, mice and rats. (See the graphic below for what is called a 'gene tree', where each line of color represents a gene and how it has changed under different circumstances.)



Goodbye and goodluck, my friend. I will miss you.



Here is Josephine with GenMedLabMom.