CRISPR - Responses to Human Gene Editing

Earlier this month I posted an article on CRISPR and asked if it would be the answer we are waiting for in the Kennedy's Disease and other rare disease communities. The opportunity for human gene editing has generated a lot of interest and questions concerning its use. Below are two comments concerning this potential breakthrough.

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May 18, 2015

National Academy of Sciences and National Academy of Medicine Announce Initiative on Human Gene Editing

Joint Statement by Ralph J. Cicerone and Victor J. Dzau

WASHINGTON -- The National Academy of Sciences and the National Academy of Medicine are launching a major initiative to guide decision making about controversial new research involving human gene editing.  Human gene-editing technologies, such as CRISPR-Cas9, may lead to promising new treatments for disease.  However, recent experiments to attempt to edit human genes also have raised important questions about the potential risks and ethical concerns of altering the human germline.  Future advances are likely to raise new questions.

Our initiative will include an international summit this fall to convene researchers and other experts to explore the scientific, ethical, and policy issues associated with human gene-editing research.  In addition, we will appoint a multidisciplinary, international committee to begin a comprehensive study of the scientific underpinnings and clinical, ethical, legal, and social implications of human gene editing.  The committee will consider and recommend standards, guidelines, and practices governing the use of gene-editing technologies in biomedical research and medicine.  An advisory group to steer the overall initiative will soon be announced.

We provided leadership in the past on emerging, controversial new areas of genetic research, such as human embryonic stem cell research, human cloning, and “gain-of-function” research.  In 1975, the Asilomar conference convened by the National Academy of Sciences led to guidelines for recombinant DNA research.  In keeping with these past efforts, we are prepared to work with the scientific and medical communities to achieve a comprehensive understanding of human gene editing and its implications in order to help guide researchers, clinicians, policy makers, and the public, here and around the world.

Ralph J. Cicerone is the president of the National Academy of Sciences, a private, nonprofit institution that provides science policy advice to the nation under an 1863 congressional charter. Victor J. Dzau is the president of the Institute of Medicine, which was founded as the health arm of the NAS in 1970.  Effective July 1, 2015, the IOM will become the National Academy of Medicine, and Dzau will be its first president.

Statement on NIH funding of research using gene-editing technologies in human embryos

April 29, 2015

Genomic editing is an area of research seeking to modify genes of living organisms to improve our understanding of gene function and advance potential therapeutic applications to correct genetic abnormalities. Researchers in China have recently described their experiments in a nonviable human embryo to modify the gene responsible for a potentially fatal blood disorder using a gene-editing technology called CRISPR/Cas9.

CRISPR-Cas9 is a customizable tool that lets scientists cut and insert small pieces of DNA at precise areas along a DNA strand. The tool is composed of two basic parts: the Cas9 protein, which acts like the wrench, and the specific RNA guides, CRISPRs, which act as the set of different socket heads. These guides direct the Cas9 protein to the correct gene, or area on the DNA strand, that controls a particular trait. This lets scientists study our genes in a specific, targeted way and in real-time.

Genomic editing is already widely studied in a variety of organisms. For example, CRISPR/Cas9 has greatly shortened the time it takes to produce knockout mouse models of disease, enabling researchers to study more easily the underlying genetic causes of those diseases. This technology is also being used to develop the next generation of antimicrobials, which can specifically target harmful strains of bacteria and viruses. In the first clinical application of genomic editing, a related genome editing technique (using a zinc finger nuclease) was used to create HIV-1 resistance in human immune cells, bringing HIV viral load down to undetectable levels in at least one individual. All of these examples of research using genomic editing technologies can and are being funded by NIH.

However, NIH will not fund any use of gene-editing technologies in human embryos. The concept of altering the human germline in embryos for clinical purposes has been debated over many years from many different perspectives, and has been viewed almost universally as a line that should not be crossed. Advances in technology have given us an elegant new way of carrying out genome editing, but the strong arguments against engaging in this activity remain. These include the serious and unquantifiable safety issues, ethical issues presented by altering the germline in a way that affects the next generation without their consent, and a current lack of compelling medical applications justifying the use of CRISPR/Cas9 in embryos. 

Practically, there are multiple existing legislative and regulatory prohibitions against this kind of work. The Dickey-Wicker amendment prohibits the use of appropriated funds for the creation of human embryos for research purposes or for research in which human embryos are destroyed (H.R. 2880, Sec. 128). Furthermore, the NIH Guidelines state that the Recombinant DNA Advisory Committee, “…will not at present entertain proposals for germ line alteration”. It is also important to note the role of the U.S. Food and Drug Administration (FDA) in this arena, which applies not only to federally funded research, but to any research in the U.S. The Public Health Service Act and the Federal Food, Drug, and Cosmetic Act give the FDA the authority to regulate cell and gene therapy products as biological products and/or drugs, which would include oversight of human germline modification. During development, biological products may be used in humans only if an investigational new drug application is in effect (21 CFR Part 312).

NIH will continue to support a wide range of innovations in biomedical research, but will do so in a fashion that reflects well-established scientific and ethical principles.

Francis S. Collins, M.D., Ph.D.
Director, National Institutes of Health

Burned Out?

This month’s newsletter from Humana had a good article for Caregivers. Some of these tips are more relevant than others for those of us living with Kennedy’s Disease. As a person with KD, I encourage my wife to become involved in other activities that she enjoys. Sometimes, her just being away from me for a couple of hours makes all the difference in the world. (Maybe there’s an underlining message here for me - J )

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Six Tips to Avoid Caregiver Burnout

It is easy to get burned out when you’re caring for a loved one. Here are some tips from WebMD.com to lower your stress and recharge.

1.   Take time for yourself every day. Try yoga before breakfast, slip out for a 20-minute walk, go to the movies, or take time for a favorite hobby. Even a short break can help.
2. Get enough sleep. Most caregivers who say their own health has gotten worse blame loss of sleep. Relaxation exercises, such as deep breathing, may help you at bedtime. If a loved one sleeps during the day but ix awake much of the night, try to take naps.
3.  Join a support group. Look for support groups related to your loved one’s illness, if possible. The local agency on aging may have a listing. Or consider joining an online community.
4. Let animals assist. Spending time with a cat or dog can be soothing to people who are sick or confined at home. Pets can lower blood pressure, reduce stress and even make elderly people more alert.
5. Turn on some music. Music and art can spark fun shared moments for you and the person you’re caring for. Familiar music can bring back memories and may lead to clapping and dancing. Art projects should be simple and safe but not too childlike.
6. Use timers and reminders. Buy pillboxes that sound an alarm when it’s time for the next dose. Try a smart phone app or an online medicine reminder. Pill organizers are a low tech option.

Update on BVS857 Clinical Trial

Below is a link to a short video update given by Dr. Fischbeck of the National Institutes of Health on Phase 2 of the clinical trial using a Novartis drug called BVS857. The trial is being held in several locations in the United States and Europe. Dr. Fischbeck uses the terms 'encouraging' and 'promising' in his comments on this study.

That is encouraging for me. :-)

"In this exclusive interview, Kenneth Fischbeck, MD, of the National Institute of Neurological Disorders and Stroke (NINDS) talks about the recent studies being conducted at the NINDS, in collaboration with Novartis, to understand, and find a treatment for, Kennedy's disease (spinal and bulbar muscular atrophy)."

http://www.raredr.com/videos/Kennedys-Disease

For more about this trial, follow this link: https://clinicaltrials.gov/ct2/show/NCT02024932

Update on 21st Century Cures Legislation

This is another important bill that everyone living with a rare disorder (including Kennedy's Disease) needs to follow.

NORD Issues Statement on Today’s Approval  of the 21st Century Cures Initiative Washington, D.C. – May 21, 2015 – The following statement was issued by Peter L. Saltonstall, President and CEO of NORD, on the approval by the House Energy and Commerce Committee of the 21st Century Cures legislative initiative and the introduction of the OPEN Act in the United States Senate.  NORD congratulates the House Energy and Commerce Committee for  unanimously approving the 21st Century Cures initiative.  As Chairman Fred  Upton (R-MI) said, “This historic day marks a big bipartisan step toward our  path to cures.”  Today also marks the introduction in the Senate of the OPEN  Act, a bill that aims to greater incentivize orphan product development. We look forward to working with the House as it considers the bill approved   today by the Committee, and with the Senate as it continues its Medical  Innovation Initiative and considers the OPEN Act. The bill approved today contains provisions that are critically important for the  rare disease community. It also puts the patient at the center of drug approval,  strengthens the FDA’s ability to streamline clinical trials, reauthorizes a critical   program for rare pediatric disease drug development, and further incentivizes  development of orphan products. We hope the legislation, which includes sorely  needed additional funding for the National Institutes of Health and the Food and  Drug Administration, will foster an environment that is conducive to the  development of new therapies and improve patients’ access to them.   On behalf of the rare disease community, NORD thanks the Committee for its  months of collaboration, thoughtfulness and hard work.  Today’s vote  underscores the bipartisan commitment to move this legislation through the  House and we hope the same spirit of collaboration leads to prompt  consideration by the Senate. Peter L. Saltonstall President and CEO, National Organization for Rare Disorders (NORD)

Show your support for NIH

MDA's Outreach Program sent out a message this week that needs to be passed along and supported by all those living with a neuromuscular disease (ALS, SBMA, SMA, etc.).

As many of you know, NIH is currently conducting a clinical trial for a treatment for Kennedy's Disease. If this phase goes well and the treatment is determined to be safe, NIH will move to the next phase and open the trial up to a larger group of patients.

Read the message from the MDA below and consider supporting the proposed increase to NIH spending.

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Increase Funding for the National Institutes of Health (NIH)

Increased funding for the National Institutes of Health (NIH) is critical to finding treatments and cures for the neuromuscular diseases that affect our community. Together, with our generous donors and sponsors, MDA is working to fund groundbreaking research and bring critical support to families. Collaboration-including leveraging federal funding-is vital to speed urgently needed treatments to affected individuals as quickly as possible.

Ensuring increased NIH funding is one of MDA's top policy priorities. Through targeted efforts and strategic initiatives, MDA is urging Congress to boost funding for NIH. Increased support for NIH is critical, as funding levels have failed to keep up with the rising costs of medical research-resulting in a 22% decrease in purchasing power since 2003, when adjusted for inflation. This lack of funding has resulted in a lower grant application success rate and hinders the ability of NIH to conduct and support important biomedical research.

With many voices carrying the message that medical research is imperative to finding treatments and cures, lawmakers have placed increased NIH funding on the Congressional agenda in both the Senate and the House of Representatives.

One example is the 21st Century Cures Act draft released May 13, 2015, by the House Energy &

Commerce Committee. This draft would authorize an increase in NIH funding and would create an NIH Innovation Fund that would increase NIH funding by $10 billion over five years. MDA applauds the bipartisan efforts of the Energy & Commerce Committee for making NIH funding a priority and appreciates the efforts of Chairman Fred Upton (R-MI-06), and Rep. Diana DeGette (D-CO-01), Frank Pallone (D-NJ-06), Joe Pitts (R-PA-16) and Gene Green (D-TX-29) to ensure that increased NIH funding is included in the draft legislation.

In addition to the 21st Century Cures Act, several pieces of stand-alone legislation in the House and Senate support increased NIH funding at various levels. MDA appreciates the efforts of every lawmaker who takes action to increase funding for medical research.

Please click the button below to urge your Congressional leaders to support increased NIH funding. 

Road Trip?

Up until a few years ago, my wife and I loved “getting lost.” It is our term for a road trip where we

don’t know where we are going and when we’ll be home. These adventures provided plenty of opportunities to expand our world, try different cuisine, and learn more about our country and its history.

Unfortunately, ‘getting lost’ is a thing of the past for us. Trips, nowadays, have to be researched and planned ahead of time. The joy of spontaneity is now missing. 

The CostCo Connection magazine this month has a good article called, “Going Mobile – Making Travel More Accessible for Everyone.” 

I found it interesting that people who use wheelchairs or other mobility devices spend $20 billion a year on travel. Another interesting number is that 24% of the U.S. population is projected to have some kind of disability by 2030. 

Cruises have become popular for those of us disabled because cruise lines have embraced this market. Currently, 14% of the disabled population has taken a cruise. The percent is much higher than the general population.

Unfortunately, a large sector of the hotel industry doesn't have the message yet. More than 10 million people with mobility challenges stay in hotels each year. The number of rooms available and services offered are still behind the times. One problem mentioned is that each traveler has different needs.

Below are some links that will be of help to you should you be planning a cruise or trip. The first one is one of the best I have found.

http://www.barrier-freecruising.com/

http://www.disabledtravelersguide.com/

http://www.independenttraveler.com/travel-tips/senior-travel/disabled-travel

What are your travel experiences (the good, the bad, and the ugly)?

Luggage Photo: Packed for travel by Ladyheart

Will CRISPR be the answer we have been hoping for?

I was reading the KDA Forum this afternoon and ran across this article in GIZMODO about CRISPR. It appears the possibilities are almost endless in regards to what you can use this for in the area of editing genomes. When I say endless, I mean finding a cure for Kennedy's Disease (SBMA). 

Excerpts from the article are shown below. Click on the title below to read the entire article.

Everything You Need to Know About CRISPR, the New Tool that Edits DNA

“CRISPR, a new genome editing tool, could transform the field of biology—and a recent study on genetically-engineered human embryos has converted this promise into media hype. But scientists have been tinkering with genomes for decades. Why is CRISPR suddenly such a big deal?

The short answer is that CRISPR allows scientists to edit genomes with unprecedented precision, efficiency, and flexibility. The past few years have seen a flurry of “firsts” with CRISPR, from creating monkeys with targeted mutations to preventing HIV infection in human cells. Earlier this month, Chinese scientists announced they applied the technique to nonviable human embryos, hinting at CRISPR’s potential to cure any genetic disease. And yes, it might even lead to designer babies. (Though, as the results of that study show, it’s still far from ready for the doctor’s office.)

In short, CRISPR is far better than older techniques for gene splicing and editing. ..."

Then, later in the article it mentioned the snipping of DNA sequences and the light bulb clicked on:  

"It is a more precise way of editing the genome...

As this point, you can start connecting the dots: Cas9 is an enzyme that snips DNA, and CRISPR is a collection of DNA sequences that tells Cas9 exactly where to snip. All biologists have to do is feed Cas9 the right sequence, called a guide RNA, and boom, you can cut and paste bits of DNA sequence into the genome wherever you want.”

This caught my attention near the end of the article. “… with CRISPR/Cas9, it’s theoretically possible to modify the genomes of any animal under the sun. That includes humans. CRISPR could one day hold the cure to any number of genetic diseases, but of course human genetic manipulation is ethically fraught and still far from becoming routine.”