Thursday, April 27, 2017

The Case for Compassion

Ironically--fighting for healthcare may stress me to death. I'm struggling to stay positive, but it helps to know I'm not alone. My Mama Bear Defense System is humming at full throttle. I'm anxious, and frequently on the edge of tears... I'd love to just take a vacation and check out, but now is not the time to take our eyes off the ball in terms of advocating for healthcare policy for those with cystic fibrosis.

The CF community engaged with lawmakers in a formidable way in opposition to the GOP's American Health Care Act (AHCA), providing feedback about the inadequacies of the legislation with over 34K calls, texts, and emails tracked through the CF Foundation's advocacy platorm. These interactions MATTER. Because of the overwhelming public outcry to the bill, the Republican party wasn't able to unite in support, and the legislation never even saw the light of day for a vote in the House. Read about the original legislation and the impact it would have on those with CF here.  All of the concerns with the original legislation still remain. The cuts to Medicaid are still intact in this amended legislation, and would be devastating to millions.


I was incredibly relieved when the AHCA was pulled from the House floor prior to a vote, but the GOP is geared up to take another shot at passing the AHCA with a new amendment. The amendment is designed to appeal to the two factions of the Republican Party that blocked the passage of the legislation the first time around.

1) Moderate Republicans represented primarily by "The Tuesday Group" in the House.
2) Ultra Conservative Rebulicans represented primarily by the House "Freedom Caucus."

Moderate Republicans from The Tuesday Group say they would have voted no on the legislation if they had the opportunity, due to the negative impact it would have on the people who vote for them.

The Freedom Caucus members, however, say they would have voted NO to the legislation for a very different reason. They want to pull the bill much further to the right--stripping away protections for people with pre-existing conditions. Their idea is to allow insurers to discriminate agains those with health conditions and charge them more $$$--which forces patients into state run high-risk pools (which have been shown over decades to be disastrously inadequate). The Freedom Caucus also wants to allow insurers to reduce their standard of "essential benefits" covered in plans.

The amendment to the AHCA makes the bill much MORE DANGEROUS for people with cystic fibrosis--or any other health condition for that matter.

"the latest proposal would allow states to apply for "limited waivers" that would undermine Obamacare's protections for pre-existing conditions. Under these waivers, states could opt out of Obamacare standards setting minimum benefits that health plans must offer and a requirement — called community rating — forbidding insurers from charging different prices to people based on health status."

The amendment to the AHCA would give states the ability to opt-out of Obamacare standards--which is exactly what my Congressman Raul Labrador--Leadership of the Freedom Caucus wants to see. In a Town Hall a few days ago, Rep. Labrador said:

For those with complex chronic health conditions like Cystic Fibrosis, health insurance must actually COVER HEALTH CARE to be effective.  Losing protections for those with pre-existing conditions and lowering the level of essential health benefits that insurers must cover may sound alright to Labrador on paper...but the policies would be "CATASTROPHIC" to actual people.  Labrador believes that people with health conditions should absolutely be forced to pay more for their insurance, and wants to bring back high-risk pools as the best method of dealing with the "less than healthy." There are decades of experience with high-risk pools to illustrate the inadequacy of this option. Returning to the discrimination of high-risk pools would be a huge step backward.

I can argue about policy until I'm blue in the face. It is much much harder for me to argue about compassion. In discussing healthcare face-to-face with Congressman Labrador in early March, he spoke about his desire to make our healthcare system "fair" to the young healthy 20 year olds who he believes are paying "too much" for insurance. I completely understand that not everyone requires the same high standard of care that those with CF need, but I also think it is extremely narrow-sighted to design a healthcare system around the individuals that DON'T NEED IT as the #1 priority. The changes proposed in the latest amendment to the already awful AHCA would do the greatest harm to children, the disabled, and the elderly--the most vulnerable in our society. What can I say to convince Labrador (and others) that it is not OK to let people suffer and/or die because they can't access the care that they need? Are we plunging into a "survival of the fittest" scenario here in the US, where there is no room for compassion? Can we actually stomach systematic discrimination against those with serious health conditions in this nation and watch this tragedy unfold with eyes wide open? The United Nations has even stepped in to warn the administration that taking away healthcare from 30 million Americans without a suitable replacement would represent both a violation of human rights, as well as binding international conventions. 

Individuals with pre-existing conditions are people with families, talents, and dreams...just like my precious Brady. This legislation would put America behind nearly every other developed nation in the world in terms of healthcare for our citizens. We can do SO MUCH BETTER, and we must demand that Congress go back to the drawing board. Interestingly, Congress has decided to exempt themselves from the most dangerous aspects of this legislation. We mustn't let hypocrisy win. Please call your member of Congress today and ask them to OPPOSE the AHCA. The CFF's advocacy action center is the easiest possible way to make those connections with lawmakers. Don't wait--follow the link to take action NOW!

Sunday, January 8, 2017

The Policy Punchline

As National Advocacy Co-Chair for the Cystic Fibrosis Foundation (with my fabulous Co-Chair Melissa Shiffman), and Mother to a 9 year old living with cystic fibrosis, my level of anxiety has been elevated to some all new heights as the dismantling of our healthcare policy looms on the horizon. A second contributor to my overall mental health crisis is the INCREDIBLE LACK OF DETAIL about what will be proposed to replace the ACA. By all sources, the 1st order of business for the incoming administration will be the repeal of large portions of the Affordable Care Act ("Obamacare").  The ACA is an incredibly large and complex piece of legislation--for the purposes of this discussion, I will focus on the portions that most deeply impact those living with chronic diseases like cystic fibrosis. Whether or not healthcare policy is  really your cup of tea, it is going to be crucial for us to UNDERSTAND and FIGHT for access to affordable and adequate healthcare and medicine as new legislation is proposed in this new era. We certainly can't afford for our needs to be boiled down to "one-liners" or lost in a jumble of confusing rhetoric. Let's detail a few of the conversations we will need to be a part of to ensure that those with CF have access to adequate and affordable healthcare coverage, accredited CF care centers, and the most effective medications. I encourage you to read the CFF's message to the community following the election.

The Affordable Care Act ("Obamacare")

Certain portions of the ACA are highly relevent to promoting insurance coverage and high quality care for those with CF.

Lifetime and Annual Benefits Caps

Unless you have personally approached a lifetime or annual benefits cap (prior to the ACA), this issue may not be on your radar--BUT IT ABSOLUTELY SHOULD BE NOW. Before Obamacare, insurers set a cap on the amount of benefits they would pay out to an individual in a single calendar year, and also set a lifetime cap on the benefits paid on an individual plan. The annual caps varied from policy to policy, but the lifetime caps were typically set between $1-2 million. The ACA prohibited insurers from setting these annual and lifetime insurance caps. 

The policy that my family held prior to the ACA was a great plan purchased through my husband's employer with a $2 million dollar cap. Over the course of the last 8 years, successful research endeavors have changed the direction of treatment for CF. For example, the last time these caps were legally allowed, KALYDECO AND ORKAMBI DID NOT EXIST.  Those with CF undergoing transplant were likely to encounter these lifetime/annual caps at the most critical time in their care, and I hope that some who've experienced this will be kind enough to leave a comment about how this affected them. 

Today, we are fortunate enough to be in an era of greater understanding and treatment of the root cause of cystic fibrosis with small molecule gene modifiers. I am acutely aware that not everyone with CF is able to benefit from a drug like Kalydeco or Orkambi right now, but the drug development pipeline is absolutely packed with compounds that are poised to move to market in the coming years. Upcoming gene modifiers are anticipated to carry the same level of "ultra-premium pricing" as Kalydeco and Orkambi. Let's break down the math for someone like my 9 yr. old son Brady--who depends on Kalydeco (among many other prescriptions!) to stay healthy.

Monthly Rx of Kalydeco = $34K
$34K x 12 months = $408K annually 
$2,000,000 lifetime cap divided by $408K/year = 4.9 years of benefits before reaching cap

Effectively, reaching a lifetime max on benefits would take less than 5 years for someone like my son Brady with that single Rx. Kalydeco has been an incredible life changing drug for him since the day he began treatment (Feb. 10th, 2012--which equates to 4 years and 11 months of prescription benefits). Without the protections outlined in the ACA, he would MAX OUT HIS LIFETIME INSURANCE BENEFITS THIS MONTH (as we just tipped over the $2 million dollar mark) with that drug alone (not counting enzymes, antibiotics, breathing treatments, etc...)!!! I want to reiterate that Brady is 9 years old, and the prescriptions he takes have allowed him to live a full healthy life. Along the same lines, any annual caps (which would be much lower) placed on benefits could potentially be maxed out by filling a single month's worth of a drug like Kalydeco or Orkambi! 

Those needing an organ transplant or spending significant amounts of time hospitalized would also be deeply affected by these caps. How would you feel if your insurance benefits were simply cut-off when you reached their pre-determined max? What would you do? If that doesn't make you stop and think long and hard about the future of caring for cystic fibrosis--I don't know what will. Allowing lifetime and annual caps to return and be legally instituted by insurers will absolutely--no doubt about it--be a deadly disaster for those with chronic diseases like CF. Until we cure CF, the thought of "part-time" coverage because of annual caps, or maxing out your lifetime of benefits in just a few years is not a scenario we want to see become a reality. CF is a chronic disease that requires high quality chronic treatment. Allowing these caps to be put back into place will effectively flush our progress toward treatment of this disease down the toilet, because access to drugs and therapies will be governed by insurance caps on benefits. Let's be clear that simply gaining FDA approval for new incredible drugs does NOT GUARANTEE ACCESS. My hands are trembling just typing this...

Pre-existing Conditions

If you were born with cystic fibrosis--you are likely aware that you have what insurers call a "Pre-existing Condition"...but did you know that the Affordable Care Act provides 3 SEPARATE and EQUALLY IMPORTANT protections for those with pre-existing conditions?

1) Insurers cannot refuse sale of a policy to those with pre-existing conditions.
2) Insurers cannot charge these individuals more $$$ for their policy.
3) Insurers cannot "carve out" coverage for those with pre-existing conditions. (**For example, before the ACA, it was legal for an insurer to sell a policy to someone with CF, but exclude all coverage relating to the treatment of the disease).

I hope it is clear pre-existing protections #2 and #3 are just as vital as #1. What good would it do to have the legal option to purchase a health insurance plan with an astronomical price tag that is completely unaffordable? Along the same lines, what good is it to be able to purchase an insurance plan, if insurers are legally allowed to carve out (exclude) vital coverage for your cystic fibrosis/diabetes/cancer?  These 3 protections were designed to WORK TOGETHER to protect the most vulnerable in our society. I'm deeply concerned about the current political banter regarding pre-existing conditions because it usually sounds something like this...

"We want to keep the pre-existing part." 

Most of the time, this one-liner is in reference to protection #1--the legal right to purchase a plan. This is precisely the scenario where we can't let our needs get boiled down to simply having the ability to buy a policy. We also need that policy to be affordable, and to cover the actual treatment of that pre-existing condition in question. It is important that both consumers and lawmakers understand what is at stake here.

I've heard some discussion about the use of "high-risk pools," as a method of insuring those with pre-existing conditions after the repeal of the ACA. This is a strategy that has been utilized in the past (before the ACA), and was a costly disaster for people with cystic fibrosis. If you think premiums are high now...wait until you are dependent on the high-risk pool rates--they are the highest of all!!! High risk patients means high priced premiums--so high that they were completely out of range for many who needed it most. I would encourage those who experienced coverage under a "high-risk pool plan" prior to the ACA to leave a comment. Past experience with this strategy has proven that reducing coverage options to high-risk pools for those with pre-existing conditions was NOT AFFORDABLE, ADEQUATE, or ACCESSIBLE. The failure to provide good healthcare under high-risk pool plans was one of the very reasons why the pre-existing protections were included in the ACA. We absolutely don't want to go backward with our rights to access better coverage plans at lower rates than those offered to high-risk pools.

Ability to Remain on Parent's Insurance until age 26

This is much more straight forward than the pre-existing and benefits caps issues. The Affordable Care Act requires insurers to allow children to remain on a parent's plan during the years they are most likely to be still enrolled in college, or have reduced opportunities to obtain insurance through an employer. Prior to the ACA, the cutoff age was 19, or 22 for those enrolled full-time in college. For those with CF, this extension has been shown to be extremely beneficial to continuity and quality of coverage. Please refer to the fact sheet in the link below for further details on this provision.

Medicaid Eligibility

1/2 of children and 1/3 of adults with cystic fibrosis depend on Medicaid. The Affordable Care Act expanded Medicaid eligibility requirements--extending coverage to many who were previously not qualified. This eligibility expansion is one of the many provisions of Obamacare on the chopping block with the planned repeal of the ACA. Because Medicaid is utilized by such a large percentage of those with CF, it doesn't take a huge leap in logic to understand that reducing eligibilty would negatively impact the CF community. Those who qualify for Medicaid through the ACA's expanded criteria could face losing that coverage with repeal of this provision. This CF Foundation blog breaks down the details of the Medicaid expansion for those with CF. 


If you or someone you love is living with cystic fibrosis or ANY OTHER CHRONIC DISEASE REQUIRING TREATMENT, I hope that you are convinced beyond a shadow of a doubt that changes to healthcare policy will have a personal impact. RIGHT NOW it is a critical time to be a part of healthcare policy discussions, and make our lawmakers aware of how these coverage issues will impact the CF community. PLEASE PLEASE PLEASE follow this link to tell Congress to protect your coverage.  You don't need to be a policy expert...the most powerful thing we can do is share personal experiences on why coverage is so vital for those with CF. We need your voice to ensure that healthcare policy changes don't become a painful "sucker punch" to our beloved community.

***For the record, I understand that high insurance premiums are a concern for many American families whether cystic fibrosis is part of the picture or not. I am not saying that this is not an important issue... but it is a FACT that rising premiums were an issue long before the ACA. I understand that the cost of premiums is prohibitive for many, and we aren't giving up on advocating for lower cost coverage!! The issues I've outlined in this blog, rather, represent the portions of the ACA that would be the most catastrophic for those with CF if repealed (which we anticipate early this year) without appropriate replacement.

Monday, October 31, 2016

Exposures and the Human Response--Partnerships for Sustaining Daily Care

From my experience, the NACFC has always been saturated with heavy science…which is fantastic, and has helped create what many may call the most incredible story of progress in medicine today.  I attended my very first Conference in 2011 to see the science for myself, and hell would have to freeze over to keep me away at this point.  In my 6 years attending this event, I’ve watched the CF research environment EXPLODE. There are 50+ clinical trials that will take place in the coming year, and more companies are entering the ring of CF drug development than ever before.  The NACFC is attended primarily by the research community and our clinical care teams, which left me feeling a bit out place occasionally attending as a CF Mom…so I faked it, and acted like I belonged. After all, my educational background is in Chemistry, so I wasn’t a fish completely out of water.  This year though, I felt a shift. The theme of “patient centered care,” and “patient driven research” came up again and again. I was completely thrilled to see 2 adult patients with CF, and the Mother of twins with CF participate live in a Plenary session and have the opportunity to address a room of 4500+ professionals who dedicate their careers to CF care and research. In every way, shape, and form—the patient voice has arrived front and center.  Acknowledgement of community participation in research and care is deeply appreciated. It has been my opinion that we, as the CF community, have the most to lose or gain—and that our voices should not only be a valued part of the discussion, but are VITAL to moving forward if we want research and care to reflect the needs and desires of the patients and families living with this disease.
This year at the NACFC, I had the opportunity to discuss a collaborative project that I’ve been a part of for the last 3 years —Partnerships for Sustaining Daily Care (PSDC). Actually, we originally began as a part of a Strategic Planning Initiative by the CFF, which brought together several committees to address the direction of the Foundation’s resources and programs moving forward. Amazing things, such as the CF Adult and Family Advisors (AFA) have resulted from these thoughtful efforts. I participated in the strategic planning process as a member of the committee addressing adherence. Basically, the CFF could see from Registry and patient reported data, that consistently completing the care regimen was an issue for many. There is also plenty of research that shows better health outcomes associated with successfully completing treatment regimens, and the Foundation saw this as an area where improvements in health and well-being might be gained WITHOUT a new drug—but by helping patients and families utilize what we already have at our fingertips.
One thing is for sure—incorporating CF care into daily life can be extremely difficult. There are numerous challenges that arise: coverage or access issues to even OBTAIN the medication, time (there are only so many hours in the day!), or mental health issues like depression or anxiety that can make completing the care regimen exponentially more difficult—just to name a few.

FACT: Completing the CF care regimen day after day is difficult.

FACT: Regular successful completion of the CF care plan results in BETTER HEALTH OUTCOMES.

FACT: Engaging and empowering patients to give input about their personal goals, and work closely with their care teams to "co-create" the care plan, results in a regimen that is more likely to be sustained. Once we walk out those clinic doors--it is all up to us to balance CF care with our actual lives. I completely understand that there are certain standards of care that our clinic teams must ethically follow, but there is also a tremendous amount of flexibility and creativity that can be employed to also allow patients the opportunity to participate in life in the ways that are most meaningful to them. After all, what is the point of it all, if we miss out on the moments that make life WORTH living?

For me, discussing some of these challenges with Brady’s care team has also been difficult. Let me be clear, I absolutely LOVE Brady’s clinical care team. They have cared for him since birth, and I consider them family! Brady’s care team is comprised of people that I admire MOST in the entire world. Even with the great relationship I share with them, being open and honest about challenges with the care regimen can be difficult because: 

1) For me (type A personality), admitting to my care team that I was having issues with the care plan felt like admitting that I'm not perfect...and that was tough.

2) Not everyone shares a wonderful relationship with their care team, and discussions around "adherence" to the regimen can take on a judgmental tone. "Why weren't you able to complete every dose of Pulmozyme last week?" can feel more like "What's the matter with you?" The tone and intention behind the communication is extremely important because... 

3) We are sensitive about these issues. Even when we miss doses or treatments, we may still be bending over backward to incorporate CF treatments into our lives.  We may have to sacrifice time with our friends, and sometimes have to say no to invitations because it just doesn't work with our CF care that day. There can be some bitterness about missing out on LIFE to care for CF. Also, because of the progressive nature of the disease, we sometimes don't succeed at reaching our goals--even when we do every single goddamn thing right. I know that as a parent, I often took it very personally if Brady didn't meet his weight or lung function goals. It made me feel like a FAILURE.

4) Clinic visits are so long and jam packed already, that bringing up a tough topic like a struggle with depression or anxiety might be the LAST thing you want to do. I know that toward the end of a long clinic visit...I would probably say or do anything just to escape, and get the hell out of there! I may not feel like bringing up my anxiety or depression at that point. These discussions can't take place as an afterthought, because that means they may not happen at all. 

5) Mental health issues, though they are getting talked about more and more, still carry a certain taboo in our society. 

As someone who has personally struggled with anxiety and depression related to CF, I think it is time to move beyond these taboos, and bring mental health out into the open, as a part of our regular clinical care. Last year, mental health was addressed in a big way, as the topic of a Plenary Session entitled: There is no Health without Mental Health. I encourage everyone to follow the link and read more about that amazing session.

FACT: People living with a chronic disease and those that care for them are more likely to suffer from anxiety or depression 

If you've lived with a chronic disease, or cared for someone who has, these statistics may not come as a surprise. Anxiety and/or depression are absolutely normal human responses to stress and trauma, which are something we are regularly exposed to dealing with CF. For me, it felt like there were sort of 3 main categories: 1) chronic stress, 2) acute stress, and 3) traumatic stress

Chronic Stress: The daily burden of care can absolutely be exhausting and stressful. Also, when a shortened life expectancy is attached to the disease, worry about long term survival and quality of life are things that can keep us awake at night. I remember when Brady was an infant, it felt like these constant worries were assaulting my brain like a machine gun. It just wouldn't stop. 

Acute Stress: There are so many acute stressors in CF, that I don't even know where to start: pulmonary exacerbations, holding a screaming child down for a procedure/blood draw/throat swab, clinic visits or hospitalizations, explaining CF to someone new, missing something important to you because of CF, the fear of exposure that can come with flu season...the list could go on and on.

Traumatic Stress: Unfortunately, living with CF can also mean exposure to traumatic stress: a massive lung bleed or lung collapse, undergoing transplant, or losing someone you care about to CF can have a major impact on mental health.  

Exposures and the "Normal" Human Response
We honestly wouldn't be human if these stressors and traumas didn't impact us...and there needn't be any judgement attached to that fact. Let's consider a couple of scenarios.

1) Your friend was seated next to someone coughing and sneezing their head off with a viral infection on a long international flight. Each cough or sneeze exposes your friend to germs, and a few days after she returns home, she becomes ill. Do you think she is weak because her body succombed to the same virus? No. Of course not. That seems ludacris.This is a normal human response. 

2) A child exposed to high levels of carcinogens in their environment develops cancer as a result. Do you blame the child for not being able to handle the pollution?... Not unless you're an asshole! This is absurd. The child's cells began dividing out of control because that is a normal human response to high levels of carcinogen exposure. 

3) A person living with a cystic fibrosis is exposed to the constant stress of the daily management of the disease, and then suffers from a massive hemoptysis resulting in a long hospitalization and time away from family, friends, and the other important things in their life. They become depressed. Do you see that person as incapable because they are struggling? A resounding NO. This is a normal human response.

4) A Mother worries constantly about the long term health and quality of life for her child because of a cystic fibrosis diagnosis. She finds support by connecting with others in the CF community, and becomes very close to other Moms in the same boat. The support helps her manage daily stress, but she suffers a major surge of anxiety when she learns that someone in her circle of support just lost their child unexpectedly due to a complication of CF. She just can't shake the fear that something similar might happen to her own child. Do you judge this Mom as weak, or incapable? Would you recommend that she just "buck up" and shake it off? I hope it is easy to see the pattern developing here. Anxiety, in this situation, is a completely normal human response. 

When I first began working on the PSDC project 3 years ago, I think I sort of assumed that feelings of anxiety and depression came as a package deal with the CF diagnosis. As a part of the strategic planning process that led to this program, our group poured through literature on how depression and anxiety in chronic illness, and particularly CF. Even though we intuitively understand that mental health is linked to our overall well-being, it made a huge impact on me personally to see data on how mental health was directly linked to lung funtion, and other measures of physical health that we attach great importance to. Similarly, I learned that the mental well-being of the care provider was linked to the physical health of the one being cared for. 

I learned that MY MENTAL HEALTH was linked to BRADY'S LUNG FUNCTION. 

That fact was like a slap in the face to me. I think it is pretty common for caregivers to neglect their own needs, and just give and give to their child or the person they are caring for.  Along the same lines, I can imagine that if you are one living with the chronic illness, there are so many physical manifestations of the disease to deal with, that the invisible mental health issues tend to move further and further down the list of priorities. This is why mental health screening and treatment in CF is important. This is one of the important reasons why we need "Partnerships for Sustaining Daily Care." It honestly wouldn't have even occured to me to bring up my own feelings of anxiety and depression in one of my son's clinic appointments, because that didn't seem like the appropriate place and I didn't think that there was anything that could be done about it anyway. In hindsight, it is easy to see that Brady's ability to successfully complete his treatment regimen as an infant and small child was entirely dependent upon my husband and I. If we suffer...he suffers. That was a big AHA moment for me, moving mental health into the "zone of legimate concerns" portion of my brain. 

As the PSDC project takes shape, our hope is to create a cultural upgrade to our clinical care that incorporates mental health into part of the landscape of a routine visit, and create an environment where we feel that we can be safe and honest discussing ANY challenges that stand in the way of completing our daily care. This isn't going to happen overnight, as this is new territory for both patients AND providers. The PSDC group decided that the best way to see these changes take place is to try and understand they we are all human, with similar goals and desires. We participated in several "empathy experiments" to help the care team understand more fully how hard it is to live with CF day in and day out. I also gained a huge amount of respect for how difficult it is for the care teams to do their jobs as well. They also face challenges and frustrations that interfere with the delivery of the best care. We learned to look at one another as people, rather than simply patient and provider. This is about bringing humanity and empathy into our care, and that goes both ways. If anything I've said in this blog resonates with you, the PSDC group would like to hear from you!  As we begin creating the ripple for this cultural shift, we want to learn from you. What does partnership with your care team mean to you? Can you think of any instances where you felt like you worked really collaboratively and creatively with your care team to acheive something great? Tell us about it. Can you recall a time when you felt like communication with the care team completely missed the mark? We want to know about that too. Please send your comments to

I also invite you to join the Adult CF and Family Advisors. Sign up and share your input! 

I had the opportunity to chat about the PSDC in an interactive Facebook Live session at the NACFC this year and you can check it out here! You'll also learn about other cool initiatives the CFF is developing to help connect our community. You can find that interview here: 

If you are having issues with access to medications as a challenge to sustaining your daily care regimen, contact CFF Compass Program for help.

Saturday, October 29, 2016

Slides from Plenary 2--Clinical Research:A Worldwide CF Community Effort

Dr. Michael Boyle wrote a fantastic narrative of the second Plenary session. Check out the corresponding slides below! My favorite part of this session was the live involvement of 2 adults living with CF, and the Mother of twins with CF! Bringing the patient voice front and center at a research focused Conference is truly groundbreaking! Enjoy!

Genome Editing Potential for Cystic Fibrosis

People always ask what new information from NACFC excites me the most. I've listed my top 3 below, and will go into further detail about one of those--Gene Editing, as the topic of this entry.

Rebecca's Top 3 from the NACFC

1) The sheer number of new correctors and potentiators appearing in clinical research has exploded! There are almost too many of them to even keep track...and they are certainly NOT all coming from Vertex. There is a robust pipeline and a competetive surge to get these compounds on the market.

2) The development of new ways to measure CFTR function and personalized drug response. Small "organoids" can be grown from rectal tissue biopsy, nasal brushings (nasopheres), or bronchial tissue (bronchospheres). Once harvested, these cells can allow researchers to test whether or not an individual might respond to a drug treatment. As the number of new CFTR modulators increases, and as we try to treat patients with rare mutations, these techniques could prove to be extremely valuable. Once the cells are harvested, they can be reproduced indefinitely outside of the body, and drugs can be tested on a person's organoids in the lab as a good predictor of a clinical response in that individual. This kind of testing could streamline early phase clinical trials, and provide the safety of testing drugs in the lab vs. in vivo. 

3) Gene therapy strategies as a potential CURE for ANY mutation of cystic fibrosis. Investigators are examining several different techniques, as seen in the slide below. This entry will focus on CFTR gene editing using the CRISPR/Cas9 system.

One method of gene editing utilizes a system call CRISPR Cas9. CRISPR stands for clustered regularly interspaced short palindromic repeats--specific targets on a gene, containing short repetitions of base sequences, followed by short segments of "spacer" DNA. Cas9 is a single DNA targeting enzyme that serves to "code" for proteins related to CRISPRS.  In simpler terms, the CRISPR can be thought of as the specific portion of DNA targeted for alteration (the section where we find the presence of the CF mutation).  Cas9 can be thought of as a tiny pair of scissors, programmed to make a cut in the strand of DNA at precisely the right spot. This is a complicated process, but is explained nicely in this video produced by the CFF and shown during the first Plenary Session. 

Dr. Hao Yin from the Massachusetts Institute of Technology in Cambridge, MA gave a talk on Thursday afternoon entitled: 

In Vivo Genome Editing: From Proof-of-Concept to Therapeutic Delivery. 

Dr Yin's study utilized mice with a hereditary liver disease (tyrosinemia type I)
caused by a genetic mutation. He was able to demonstrate that CRISPR cas9 mediated correction of a genetic mutation in live mammals was truly possible, and has the potential for correction of human genetic diseases like CF.  As seen in the video, gene editing is a complex process. In this study, Dr. Yin combined lipid (fat) nanoparticle mediated delivery of Cas9 mRNA (messenger RNA) with adeno-associated viruses, and a repair template to induce gene repair in living mice. He was able to show that the mice exhibited short-term expression of the Cas9 nuclease by in vivo mRNA delivery, which provided efficienct on-target genome editing, and reduced off-target editing (altering the genome at unintended sites can obviously be problematic!). 

This proof-of-concept study is extremely exciting, but several challenges still remain. Two primary issues that investigators have always struggled with in regard to gene therapy strategies are the precision and specificity of targeting, and the method of delivery inside the nucleus of cells.

One method of getting information through the cell membrane to the inside of the cell is to use a modified virus to sort of "infect" cells with new information.  

It is profound that investigators have shown gene editing techniques may be successfully performed in living mammals, but there is still considerable progress to be made before we see these therapies in humans. At last year's NACFC, I also shared my excitement about development of these new gene therapy techniques. I'm really optimistic that progress will continue to accelerate in the coming year, and more exciting trials will be reported in 2017!