BU, Harvard researchers bootstrap a new approach to Alzheimer’s R&D

Armed with $1.5 million in grant money from the NIH, a pair of investigators at Harvard Med and Boston University are bootstrapping a small biotech upstart with an eye to pursuing candidate selection in animal studies for a new approach to treating Alzheimer’s disease.

Alzheimer’s so far has proven to lead to the valley of death for a multibillion-dollar effort by Big Pharmas looking to even slightly bend the curve on cognitive decline among patients. So a 7-figure initiative by a virtual biotech in the late stages of a preclinical neurodegeneration program comes with plenty of obvious concerns about the risk of failure. 


The company, Klogene, is concentrating on Klotho, a protein that has been run through a variety of preclinical programs, demonstrating potential for a range of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and ALS as well as multiple sclerosis. The growing anti-aging research community has also been enthralled by early signs that increased levels of Klotho make mouse models smarter--the kind of overall cognitive enhancer that may just help increase a healthy life span for the masses.

(Cue the required red flags against hyping anti-aging compounds. Early-stage research is almost always promising, clinical development is always hard. But this is where the rubber hits the road in creating new clinical drug programs.)

Back in 2014, Carmela Abraham, a professor of biochemistry and pharmacology at Boston University School of Medicine and co-founder of Klogene, published a study that demonstrated how Klotho protected neurons in a petri dish. It was a simple test, and one that she followed up on with additional work on mice showing increased levels of Klotho helped mouse models for Alzheimer’s perform “even better than wild type, completely normal mice,” she says.

The basic idea here is that Klotho can be neuroprotective, enhancing cognition even in the presence of “wall-to-wall” amyloid beta clusters that are widely suspected as triggers for the disease. Co-founder Kevin Hodgetts, an assistant professor of neurology at Harvard Medical School and director of the Laboratory for Drug Discovery in Neurodegeneration at Brigham and Women’s Hospital, screened out a variety of compounds and now the two plan to do some additional mouse work reviewing the best candidates for clinical development.

“The grant is to fund the animal studies to push better compounds into AD (Alzheimer’s) models,” Hodgetts tells me. And Abraham notes an interest in examining the drug for both amyloid beta as well as tau, the other prime suspect behind the memory-wasting illness. This is a target that also has demonstrated promise for remyelination, says Abraham, an emerging field in R&D focused on reversing the effects of multiple sclerosis.

For one virtual biotech, that covers a whole series of Holy Grails in R&D. Right now, the plan is to hire two or three staffers for a dedicated lab, says Hodgetts. Then as they pursue animal studies on their compounds, they can follow up on discussions with pharma execs and venture groups about possible next steps.

They don’t expect to pursue this into the clinic themselves, says Hodgetts.

It’s a long journey, barring an early disaster that could scuttle the project, but it’s the kind of effort that’s likely to garner considerable attention … if Klogene continues to make progress. 

- here's the release