Toshifumi Yokota, a young man with a winsome smile and a bright future, is changing the face of translational research in duchenne dystrophy. Working with the dystrophic dog, he is our morpholino, exon-skipping expert. Toshi, as we call him, is the first author on the recently released Annals of Neurology article that is causing a sensation in the duchenne advocate and science world. This article shows the first multi-exon skip and the first large animal proof of concept (see March 15th blog and CNMC press release for details. See also videos of dogs with and without treatment)
Trekking back and forth between Kodaira, Japan, where his animal research is based and Washington DC, where he does bench work and analyzes data, Toshi is part of the team responsible for making sense of what the morpholino research is telling us. Working at Children’s National here in Washington DC, Toshi has access to the one of the leading scientists in duchenne research today. He is mentored by Eric Hoffman, a member of the original Harvard team that discovered the dystrophin, the mutant gene causing duchenne dystrophy.
Toshi ‘s work is crucial to the future of duchenne dystrophy clinical trials and development of a first treatment for our boys. Among the questions he and the research teams will be answering are:
• What are the optimum number of exons to be skipped at one time?
• The large dose of morpholinos given to the dogs is nontoxic. Can we be assured there will not be a toxic response is the clinical trials?
• How about with petide conjugated or vivo-morpholinos?
• What is the minimum dose necessary to have a therapeutic effect?
Toshi’s mother and father came from Northern Japan and they moved to Tokyo where Toshi grew up. He went to Tokyo University and majored in Zoology. In graduate school, he studied under the mentorship of Dr. Shin’ichi Takeda, MD, PhD. Toshi was eager to work with Dr. Takeda because of his stellar reputation and because his lab was known for its leading edge research work and state of the art equipment.
Toshi met his wife-to-be, Rica, at University over a decade ago. Married last year on Guam, the newlyweds live in Odenton, Maryland.
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6 comments:
Marie,
When will they be answering these questions:
" Among the questions he and the research teams will be answering are:
• What are the optimum number of exons to be skipped at one time?
• The large dose of morpholinos given to the dogs is nontoxic. Can we be assured there will not be a toxic response is the clinical trials?
• How about with petide conjugated or vivo-morpholinos?
• What is the minimum dose necessary to have a therapeutic effect? "
Thanks,
Ofelia
Evan as I write this, the answers are being sought. Some of the answers require research and some require consensus - like the dose - we believe it is per body weight and others believe it is per body area. As for PMOs and vivo morpholinos - the PMO research has already been started. Now we wait for results, write it up and respond to any reviewers request for information. From PMOs we move on to vivo-morpholinos - the more times we go through this the better the process will be and the quicker we can navigate the systems.
cheers!
Marie
So Marie, are you ahead or behind the PPMO work done by AVI. In terms of timing, will all your work help speed up the PPMO trials or not. Will you be able to have results before they complete the preclinical work skipping exon 50?
Hello Ofelia,
I'm going to try to get a better answer to this first question because my answer is I believe any PPMO work being done with the dog is being done by us. AVI or Genetools is supplying the PPMOs. I don't know which.
The science community will do clinical trials with PMOs before any clinical trials are done with PPMOs. And as for your third question, is there anyway
Marie, I am confused now. During the last AVI conference call, they said that the clinical trial using PPMO skipping exon 50 AVI-5038 http://www.avibio.com/duchenne_muscular_dystrophy.php (work funded by Charley's Fund) will start next year (IF the preclinical results are fine of course). They expect the preclinical work to be completed by the end of 2009. This means that the clinical trial using PPMO will run parallel with the UK trials skipping exon 51 using PMO (which already started). Then, what do you mean by "The science community will do clinical trials with PMOs before any clinical trials are done with PPMOs."?
I do understand that your group is the only one doing research in dog. I thought that AVI-5038 is tested in mouse by AVI as we speak and that is all they need to be get approval for clinical trial. Sure, it would be great if your results in dog could be available this year also!
Sorry for so many questions, I am just trying to estimate the time...
Hi Ofelia,
You've hit the nail on the head. The reason I said "scientific community" is because I only know about the work we are doing and cannot speak about others' work, especially the future. As soon as I have something more tangible to share, I will be on it!
thanks
Marie
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