It’s a common refrain in dementia studies: “We should have treated them earlier.” It’s why treating neurodegenerative diseases has been so difficult, Gerhard Koenig, Ph.D., told FierceBiotech.
“We believe that the challenges in treating neurodegeneration stem from targeting disease pathologies rather than root causes such as lysosomal dysfunction, as well as from treating patients too late in their disease when significant damage has already occurred,” said Koenig, CEO and co-founder of Arkuda Therapeutics, in a statement.
Arkuda is trying to change that. Armed with $44 million from the likes of Atlas Venture and Pfizer Ventures, the Cambridge, Massachusetts-based biotech is going after progranulin, a protein that plays a role in neuronal health and the function of lysosomes—organelles involved in removing waste from cells. Its first target? GRN-related frontotemporal dementia (FTD-GRN), an inherited form of dementia.
It’s starting with FTD-GRN because it’s an autosomal dominant disease, meaning everyone who has a faulty copy of the GRN gene will have low levels of progranulin and develop dementia, typically in their 40s or 50s. Here, progranulin is both the biomarker and the target—Arkuda is using progranulin levels to identify patients who have FTD-GRN and developing small molecules to boost those levels and return lysosomes and neurons to health.
Arkuda has shown the approach works in preclinical models and hopes to be testing it in humans in 2021, Chief Business Officer Andy Hu told FierceBiotech.
“The series A is designed to enable us to take our lead program all the way through phase 1b proof of mechanism in humans … We’re also doing work on better understanding of the biology around progranulin, granulin [its subunits] and, more broadly, in the lysosome and we expect to yield some other interesting directions we can take future programs,” Hu said. “We’re also thinking about other potential clinical applications for our lead program.”
The company kept mum on what those other applications may be, but Koenig said it has “very concrete ideas and internal data” to point it toward its next programs. These could include Alzheimer’s disease, in which the bulk of research has targeted the buildup of amyloid and tau proteins in the brain.
When asked why Arkuda chose FTD-GRN rather than something like Alzheimer’s disease for its first focus, Koenig emphasized the importance of discipline.
“We can have big dreams of what we want to change, but we have to be more precise in our initial approach … We need to be disciplined about what we know, which mechanism we are addressing and then later on, look at additional things,” he said.
“We often talk in these areas about gain of toxic protein function. That is not what we are treating here,” Koenig said. “We are treating the loss of a protein function … I personally believe it’s a big difference than going after reducing something that is already deposited. It’s a differentiated approach, trying to intervene early before the organ is failing and it’s too late.”