Scientists working on rare disease research are doing “hand-to-hand combat with one gene and one mechanism at a time,” said Anna Greka, Professor of Medicine at Harvard Medical School and the director of the Kidney Disease Initiative at the Broad Institute of MIT and Harvard.
But Greka hopes to pivot from hand-to-hand combat and use more easily accessible tools instead. She spoke to NPF Covering Rare Disease Fellows about how she’s working on breaking the chains of inherited rare diseases.
“Maybe we can use our scalable tools to try to figure out how many of these diseases have something in common. And once we understand that common pathway, what I call a nodal biological mechanism, then maybe we can develop a therapy that will in turn help many of these diseases at once rather than doing them one by one.”
Greka, whose main focus is kidney disease, wants to address as many rare diseases as rapidly as possible.
“This is the mission of the new initiative called Ladders to Cures,” she said.
The Ladders to Cures collaborative includes scientists, hospitals and universities in the Boston area. But Greka wants it to go national and international in hopes that with more systems involved, more treatments will be available.
In July, Ladders to Cures held its inaugural symposium, which sparked another collateral initiative. Project RADICAL, which stands for Rare Disease Cures Accelerator, is working to simultaneously interrogate all 8,000 genes causing rare genetic diseases.
“We hope to actually introduce these mutations into human cells and then study them with different profiling technologies that we have available to find those shared nodal biological mechanisms. We’re trying to take 8,000 things and put them into bins of 50 here, 200 there, 500 there,” said Greka.
“What are the ones that are more like each other so that they presumably share this nodal biology,” she said. “Once we have these, then we can identify the specific molecular nodes and then build therapies specifically for these nodes that will now serve all of the diseases that were binned together.”
Everything that is generated from this project will be put into the public domain, Greka said.
“This will be shared freely and openly with everyone in the world, patients, physicians, scientists, anyone on the planet who wants to mine the dataset that we will generate will have access to this information. So, this is the project that we’re building to try to accelerate progress in this space.”
Greka said one of the big pushes for the Ladders to Cures initiative is to try to solve the hard problems. Part of this means recognizing that there are scientific and biological barriers to fixing these problems, as well as societal problems – like the cost of therapies.
That’s why she’s an advocate for small molecule therapies – pills. Although they seem “old-fashioned,” they are some of the best therapies and ones that can be manufactured more cheaply with room for accessibility for everyone, she said.
“As we’re excited about the new technologies, we also should think about the older technologies that are still very efficacious and interesting and potentially can democratize access a little bit more easily as we move forward.”
Access the full transcript here.
This training is sponsored by Fondation Ipsen. NPF is solely responsible for the content.
