CRISPY

As I’ve written before, I was diagnosed with muscular dystrophy in 1985. Science and technology has come a long way since then, but in some ways, not so much. Let me take you on a journey through time and where my mind has been wandering recently. In 1985, there was no effective treatment for any of the 40+ known types of MD. Since then, lab mice have been “cured” over and over again, so how is it that 40 years have passed and there is still no effective treatment for the 40+ known types of MD? Based upon science, some research, society and my own pea-brain, here is what I think:

1. Treating ANY disease in a human is WAYYY harder than we all think.
   • 1990 was the year that I first thought I would be cured soon. You see, scientists had made a breakthrough and decided that something called “myoblast transfer” was the ticket. This was pre-internet, and so I learned this from my trusty Quest magazine, published quarterly by the Muscular Dystrophy association, the only organization involved with MD at the time (think Jerry Lewis Telethon). The plan was to take immature healthy muscle cells, grow them in a lab and then inject them into human muscles, so they could “mix” with the unhealthy muscle cells to form hybrid cells that would improve function and strength.
     • Two problems emerged quickly: First, the immune system killed them off, since they were “foreign” in the body, and second, hundreds, if not thousands of injections would be needed in big muscles to make any difference which also meant swelling, infection risk, and a shitload of pain. Maybe not a cure so much….but it worked in lab mice.
   • No problem. The main issue in the most severe form of MD (Duchenne), is a missing protein called Dystrophin (clever). Let’s just make the protein and have a tool to get it to the muscles. Attach the protein to a vector, like a virus. Yes…take the common cold virus, strip it of its damaging properties, then attach the Dystrophin protein and send it in to the body. It works in the mice. This can’t miss. Besides, Y2K wasn’t even a thing and now it’s 2001…we got this.
     • Not so fast. All of this is microscopic, but it real life terms, many genes in our bodies can be imagined as an inch or two of code. The Dystrophin gene is the size of a meter stick. So now we know we need to fix the kitchen sink, but all we can do is pour big nuts and bolts down the drain and hope for the best. Didn’t work. As I write this, there are researchers still working on cutting the gene down to a workable size, but it’s proving extremely difficult even 20 years along. I have visited with a few of these scientists and I marvel at their focus, precision, and perseverance. We joke about the mice. They cure the mice about once a month it seems.
   • As time marches on, the U.S. government has been tapped to help fund interesting muscle research in soldiers: the Department of Defense works in muscle research to study increased strength, stamina, and carrying loads of soldiers in the field. That research involves steroids, as well as turning off genes to allow muscles to grow faster and stronger (Myostatin cow is in the photo). Professional athletes and their agents have also kicked the tires around up regulating muscle tissue and related proteins to Dystrophin. For MD individuals, it’s survival….for soldiers and athletes, it’s a performing edge, but hey, we have mice that look like Arnold Schwarzenegger now. Cows too.
     • Time will tell. Some of this research is frightening and moving along leads me to where we are now…
   • Several pharmaceutical companies big (Pfizer) and small (Sarepta) have entered the rare disease space now to work on gene therapy and gene editing. We have progressed in our knowledge of MD to the point where companies can feasibly manufacture drugs to improve the lives of people with sickle cell anemia, cystic fibrosis, blindness, certain types of cancer, SMA, and other rare diseases, however these emerging treatments are very expensive. If you google gene therapy, you will find a whole industry emerging. These companies smell money. Insurance companies smell fear, as some of these treatments run at $1,000,000 a year or more for life. Who pays and how is a subject for another post. A few gene therapies have been approved by the FDA, and a couple are for Duchenne MD. I know people who are on them. None of them can say for sure if they are working or not. Labs need to prove “clinical benefit” before a drug goes to the FDA for approval. How do you measure that with a million variables present in the human body? If you are going to die from Duchenne and you know the medicine isn’t harmful, would you try it anyway just in case? It has been clearly demonstrated that right now there is no way to rebuild muscle tissue that has already been lost. This means old men like me aren’t going to walk, jump, or run anytime soon. Instead, the companies look to buy time, slow the progression and keep researching. This is good. I have reason to hope. Meanwhile they hold clinical human trials on children who have less disease expression, healthier muscles, and more chance of “showing” clinical benefit so the companies can report to their shareholders that we are “getting closer to a treatment.” I understand it on all sides. Currently, in Ohio, there is an ongoing human trial of a drug compound specifically for my type of MD. The man leading the research is 82 years old and brilliant. He’s been at this since he was in his late 30’s. You see it’s a slow process.
   • Finally, one of the newest buzz words in my research world is CRISPR. Maybe you’ve heard of it. This latest magic bullet (excuse my cynicism…see 1990) is advertised as “DNA splicing”, “precise gene editing”, and “turning genes on and off like light switches without altering their sequence.” What is also true is that CRISPR is very new and not even close to being understood. It can also act like a rogue drone and strike next door to where it’s supposed to in and around the cell, and/or take out more or less than it’s supposed to. In short, it causes mutations, some understood and some not. It’s the Wild West, but while researchers and governments debate the ethics around this shiny new toy, countries with more relaxed laws are forging ahead with CRISPR experiments. It has been used to breed fish that glow red. It has been used to breed frogs with 4 eyes, and it has been used to breed chickens to contain more meat. Recently, a researcher from China completed a 3-year prison sentence for using CRISPR technology to breed babies born with resistance to the gene that can cause HIV. Google that and you will find some crazy shit ranging from religious points of view, to superhuman babies coming soon. Let’s see where this goes.
2. Time, and experience have taught me that nothing is ever as good or bad as it seems. I don’t think we will have a cure next week anymore than I believe that the NBA will genetically engineer men to be 8 feet tall. One thing is certain though: Science moves forward slowly and surely. I have hope, research is exciting and maybe I will purchase a laboratory mouse that has MD and cure it in my living room using my kids Lego’s, Uncle Mike’s computer skills and a glass of scotch. 12-year. Many good things develop slowly.

Stay safe, stay crispy, and stay tuned.