Managing Editor’s Note: At a recent gathering in Washington, D.C., Jeff learned President Trump is working on a new initiative – something Jeff calls “Project MAFA.”
It’s a plan that could return America to a “new” gold standard… smash our debt… and unlock a Golden Century.
The implications are huge. And, as part of this plan, President Trump has devised a way for trillions of dollars to flow into America’s coffers.
Jeff’s airing the details in an urgent briefing next Wednesday, July 16, at 8 p.m. ET. He’ll share all he’s learned about Project MAFA and how you can position yourself ahead of the oncoming surge… Just go here to automatically sign up.
One of the most incredible and heartwarming stories I’ve been following over the last six months or so is that of Kyle Patrick Muldoon Jr., or simply “KJ.”
KJ was born last year with a very rare genetic disease – carbamoyl phosphate synthetase 1 (CPS1) deficiency. KJ’s disease was discovered within his first two days of life at the Hospital of the University of Pennsylvania.
A doctor noticed that KJ had become lethargic and wasn’t eating. This prompted the doctor to check KJ’s blood ammonia level, which is often used to check for metabolic diseases.
What he found revealed KJ’s condition…
KJ’s blood ammonia levels were extremely high.
KJ at the time of his diagnosis | Source: Children’s Hospital of Pennsylvania
They quickly moved KJ into the Children’s Hospital of Pennsylvania next door to diagnose and hopefully treat KJ.
One of the first tests the team ran was to get a DNA sample and sequence his genome. This enabled the genetics team to quickly identify the genetic mutations associated with CPS1 deficiency.
The mutations that cause a CPS1 deficiency only occur in about 1 out of every 1.3 million births in the U.S. And because it’s so rare, there’s not a commercial market large enough to justify the time and money required to develop a genetic therapy and take it through clinical trials.
Even finding enough patients for trials could prove to be impossible.
KJ and his family were fortunate to be at a hospital with strong genetics and metabolic disease organizations that were willing to pursue a genetic therapy for KJ.
The problem for KJ was that the CPS1 gene provides a critical, lifesaving function for the human body. When our bodies break down the protein in the food we eat, one of the byproducts of that process is ammonia.
Normally, our bodies produce a CPS1 enzyme in our livers that converts the ammonia into urea, which we pass through our urine. But anyone with a CPS1 deficiency can’t break down the protein in a healthy way.
Ammonia builds up in the body, which can lead to brain damage, a coma, and, eventually, death. Historically, the only possible treatment was to replace the liver. But to do that, a patient has to be at least one year old and stable, neither of which was the case for little KJ.
The medical team put KJ on a low-protein diet and some medications to help control the ammonia levels. They also put KJ on dialysis to clear out the ammonia from his system.
The goal was simple: Buy the team enough time to develop a genetic therapy to save KJ.
I can’t imagine what KJ’s family was going through at the time. But from the sidelines, I was extremely optimistic.
Having been researching CRISPR genetic editing technology since 2012 and tracking all major developments and companies in the field for more than a decade, I knew that the team could develop an effective therapy.
And they did…
The team used a form of CRISPR technology referred to as base editing.
Base editing allows the swapping out of letters for other letters in our DNA. The technology is being pursued by BEAM Therapeutics (BEAM), a promising early-stage biotech company that has been in one of my model portfolios in the past.
I actually wrote about a recent win for the team at BEAM Therapeutics in The Bleeding Edge – Beam Us Up, Biotech, and their incredible progress developing a treatment for a potentially fatal genetic disease that affects the lungs and liver.
In KJ’s case, because the genetics team knew exactly what the mutation was and what a healthy sequence should look like for the CPS1 gene, they were able to design a genetic therapy for him.
It took about six weeks of work to develop the actual base editing gene therapy for KJ. But the more time-consuming part of the process was manufacturing the therapy.
This was performed by Integrated DNA Technologies, a company that was acquired by Danaher (DHR) back in 2018.
Unable to manufacture just a single dose, Danaher had to manufacture at a scale of about 100 doses of the therapy.
With the therapy in hand, the team tested it on monkeys to determine that it was safe. They also engineered mice with the same mutations that KJ had and tested the gene therapy on them as well.
The results were positive in both cases, and the FDA moved with remarkable speed, authorizing the use of the therapy, approving it within just a week.
The final safety test was conducted ex vivo (in a lab), whereby the medical team tested the therapy on some of KJ’s liver cells to determine the efficacy of the genetic edits.
That tacked on a few more weeks of work, but the results were positive, the correct edits were made, and there were no significant off-target edits either.
So, by the time KJ turned six months old, he was able to receive his CRISPR genetic therapy in vivo (direct into the body) via a lipid nanoparticle delivery mechanism, which was delivered to KJ via an IV.
And here’s the most wonderful part of the story…
Within just a few days of his first infusion of the genetic therapy, KJ was able to tolerate more protein in his diet without any dangerous spikes in ammonia production. And because he was able to consume more protein, KJ began to grow… quickly.
Over the following two months, KJ received two more infusions of the therapy via IV and was recently allowed to go home with his family.
It would be inaccurate to say that KJ has been completely cured, but his disease has been significantly minimized. And of course, there is still more work to do, monitoring how KJ’s body adjusts to the genetic edits that were made. As he becomes healthier and stronger, his CPS1 deficiency may be resolved entirely.
What makes this such an incredible story is that, start to finish, KJ’s medical team was able to design, engineer, manufacture, test, get FDA approval, and administer a lifesaving genetic therapy within just six months.
We have the tools and technology to do this.
And now that a therapy has been developed for CPS1 deficiency, the world has a treatment for this rare disease whenever it presents itself.
It took an army of people and organizations to make this happen. The whole process was full of friction and required extraordinary efforts of collaboration and coordination for something like this to happen.
KJ was lucky. Most aren’t.
And that’s precisely what needs to change.
When it comes to diseases like KJ’s, time is of the essence. Favorable outcomes often hinge on early diagnosis and treatment, and being fortunate enough to have the right motivated team or a whole lot of money.
Right now, personalized precision medicine is at our fingertips thanks to genetic editing technology.
Diagnosis for potentially life-threatening genetic diseases can happen within days of birth using DNA sequencing, instead of months or even years until symptoms of a disease emerge.
Potential treatments for these diseases can be developed, tested, and administered faster than we’d have ever imagined would be possible before this technology.
If there was ever an obvious argument for conducting a DNA sequencing at birth, it’s KJ’s story. He’s alive and healthy today because of it.
Our medical system needs a radical overhaul. Genetic testing, artificial intelligence-powered genetic therapy design, and testing should be widely employed. Genetic therapy manufacturing needs to be expanded, accelerated, and designed in small batches for individuals.
And the FDA needs a completely new organizational construct and process to institutionalize accelerated approvals for individual therapies.
Precision medicine is the future. We have the technology.
Our regulators, healthcare systems, insurance companies, biotech companies, and regulators need to step up and redefine their organizational structure, workflows, and business models to bring us the healthcare of the future.
It is long overdue.
KJ is just the start.
Source: Children’s Hospital of Philadelphia
Trust me, it will be worth it.
Jeff
The Bleeding Edge is the only free newsletter that delivers daily insights and information from the high-tech world as well as topics and trends relevant to investments.
The Bleeding Edge is the only free newsletter that delivers daily insights and information from the high-tech world as well as topics and trends relevant to investments.
