From a series profiling researchers and innovators at Boston Children’s Hospital
He’s a big thinker focused on harnessing the hyper-small. Daniel Kohane, MD, PhD, is a leading drug delivery and biomaterials researcher, leveraging nanoparticle technology and other new vehicles to make medications safer and more effective.
It’s not quite what he had in mind as a child. He dreamed of studying life forms in remote galaxies.
But when he became aware of the constraints of relativity, he re-focused his ambitions, ultimately concentrating on innovations in drug delivery. Here’s what he told us. …
You have a drug. You know what you want it to do and where in the body you need it to go. But when you inject it into a patient, how can you make sure your drug does what you want, where you want, when you want it to?
Growing up, my grandmother’s eyes were always a problem. For years, she was losing her central vision to glaucoma, and numerous surgeries and treatments did not seem to help. Later in life, she could not see my face but could always tell who I was when I was close.
Why? First, the medications are typically delivered as eye drops, and the drops themselves can cause stinging and burning. The drops also contain preservatives that can cause ocular surface disease.
Perhaps most importantly, latanoprost and other glaucoma drugs halt the disease’s progression but do not reverse it. Taking the drugs does not provide positive feedback that will motivate patients, such as relieving pain. …
Getting drugs where they need to be, and at the right time, can be more challenging than you think. Tumors, for example, tend to have blood vessels that are tighter and twistier than normal ones, making it hard for drugs to penetrate them. Despite decades of research on antibodies, peptides and other guidance methods, drug makers struggle to target drugs to specific tissues or cell types.
And even once a drug arrives at the right place, the ability to fine-tune the dose so that the drug is released at the right time and in the right amount remains an elusive goal.
What’s needed is some kind of trigger, a stimulus that a clinician can turn on and off to guide when a drug is available and where it goes to make sure it does its job with the fewest side effects.
Today we bring more good news: Following a successful Phase III trial, rFIXFc recently received the green light for marketing from the FDA and from Health Canada.
Developed by Biogen Idec under the trade name Alprolix™, rFIXFc—a modified version of clotting factor IX—is the fruition of a technology first envisioned by three researchers—gastroenterologists Wayne Lencer, MD, of Boston Children’s Hospital, and Richard Blumberg, MD, of Brigham and Women’s Hospital, and immunologist Neil Simister, DPhil, of Brandeis University—for large protein drugs. Their idea: to extend the drugs’ half-lives by protecting them from being ground up by cells. …
Last week, Boston Children’s Hospital’s Innovation Acceleration Program hosted a jam-packed Innovators’ Showcase where teams from around the hospital networked, traded ideas and showed off their projects. Here are a few Vector thinks are worth watching.
1. An imaging ‘biomarker’ after concussion
Thirty percent of people who suffer a mild traumatic brain injury—a.k.a. concussion—have ongoing symptoms that can last months or years. If patients at risk could be identified, they could receive early interventions such as brain cooling and anti-seizure medications. New MRI protocols that can measure free, non-directional diffusion of water, coupled with sophisticated analytics, are achieving unprecedented pictures of what happens inside the brain after injury. …
Getting drugs to stay in the bloodstream longer is a big deal when it comes to treating chronic diseases. You see, a drug’s half-life—the time it takes for half of a given dose to be cleared from the body—determines how long its effect(s) last.
If a drug’s half-life is short—meaning it’s cleared quickly—patients will have to take the drug frequently. Given that someone with a chronic condition could be on the medication for many years—say, patients with severe hemophilia, who endure frequent infusions of clotting factors—a short half-life can translate into high cost. Depending on side effects and how the drug is administered, quality of life may also suffer.
About half of people with diabetes develop peripheral neuropathy. The most common form, small-fiber neuropathy, generally starts in the feet, causing pain, odd sensations like pricks and “pins and needles,” and—the most worrisome feature—a loss of sensation that can increase the chance of ulcers and infections.
In some cases, that may lead to the need for amputation—as happened with my diabetic great-grandfather whose numbed feet, unbeknownst to him, got too close to the fire.
While there are some treatments to reduce pain, there’s nothing that restores sensation. Nor do any existing treatments address the underlying cause of the neuropathy: the degeneration or dysfunction of the endings of the sensory neurons in the skin. …
Grab a garden hose. Put your thumb over the end, but not all the way, and turn the water on. What happens? The water coming out of the hose gets squeezed as it tries to push past your thumb, putting a lot of force on the molecules in the water and making a big spray.
Now do the same thing with an artery: Partially block it with a clot and let blood flow through it. In this case, the force you’ve created in the artery could be lethal—creating fertile ground for blood clots that could lead to a stroke or heart attack.