We often talk about personalized medicine here at ISB. It’s become a bit of a buzzword in the research world, and buzzwords often lead to a healthy amount of criticism. Mike Joyner, the author behind a well-shared NYT editorial “’Moonshot’ Medicine Will Let Us Down” recently joined us for a day of conversation and gave a talk summarizing his views which I might loosely paraphrase as:
1. We shouldn’t be so focused on genetics
2. Gene targets haven’t done much as far as therapeutics
3. Most of the community isn’t really equipped to understand genetic risk
Lunch with Mike got me thinking…thinking that I didn’t really agree. Because I knew from my experience that gene therapies were in fact panning out in small but miraculous ways, and those stories should be shared and lifted up. So I want to offer up what I believe stands as a great example of gene-targeted therapeutics.
Ionis Pharmaceuticals was founded in 1989 with the goal of commercializing a type of gene therapy called antisense oligos (ASOs). ASOs are small 12-25 nucleotide oligos. They are chemically modified and designed to target and bind specific mRNA targets (the gene transcript). Because mRNA must be single stranded to be translated into protein, the binding interaction effectively diminishes protein levels. These drugs can be applied to genetic diseases where a bad copy of the gene makes a mutated protein; if you can stop making mutant protein, you can fix the problem.
Antisense therapies have been developed by Ionis and others to treat a variety of diseases. You can check out the Ionis pipeline here.
Recently, Ionis’ drug nusinersen, designed to treat Spinal Muscular Atrophy (SMA) in pediatric and adult patients, was approved by the FDA. Now called Spinraza, in targets the SMN2 gene. This drug was discovered in a collaboration between an academic research lab at Cold Spring Harbor (Adrian Krainer) and Ionis. I want to emphasize the collaboration because this wasn't just something that happened within a biotech or within industry. It required academic researchers as well.
A family I am acquainted with has two adorable little boys, Harper and Hendrix, who are both affected by SMA. Type II SMA begins to affect children between 6 to 18 months old. Typically babies born with SMA – about 1 in 10,000 – appear normal and achieve all the beginning developmental milestones, such as learning to roll over or sit up. But before their second birthday, these babies start to regress and have trouble with basic movements including swallowing. Proximal muscles and lung muscles are often the first to be affected. Parents live in fear of a respiratory illness or infection, which often results in long visits in the ICU for their children.
Harper and Hendrix rely on wheelchairs for mobility. But luckily for these two little boys and so many other families, there is hope. In a clinical trial for Spinraza that led to its approval, 40 percent of children on the drug re-achieved the ability to sit, crawl and walk. They were doing things parents never thought they would see their children do again.
The Ramos family has been traveling to Seattle every couple of weeks to give Harper and Hendrix infusions of Spinraza. It is not an easy treatment to receive, as it must be infused into the spinal fluid. On Facebook, their parents share videos of the boys grabbing objects for the first time and holding hands for the first time since their symptoms began. It is, quite simply, a miracle treatment and makes me so happy to see their progress, but also to believe in science and research again and the difference it can make.
Harper and Hendrix at Seattle Children's for Spinraza treatment
From their mom, “Do you believe in miracles…watch this. These boys haven’t been able to roll over since they were 18 months old. Look at their smiles and determination! Through hard work and love their treatments are working.”
Harper and Hendrix with their older brother at Seattle Children's hospital.
A special thank you to the Ramos family for allowing me to share their story.