A rare inherited form of early-onset dementia that typically strikes people between the ages of 45 and 65 is the focus of a new Cambridge biotech startup that was officially launched Thursday.
Arkuda Therapeutics has been incubated by Atlas Venture since February of last year. It has $44 million in venture capital raised by Atlas and the venture capital arm of Pfizer, the pharmaceutical giant.
Arkuda has developed several experimental drugs for the disease, GRN-related frontotemporal dementia (or FTD-GRN). The disease afflicts about 5,000 patients in the United States and causes rapid nerve cell loss in the frontal and temporal lobes of the brain. That can affect personality, behavior, language, memory, and movement, according to company executives.
If someone inherits a single defective GRN gene from one parent, he or she has a 90 percent chance of getting the disease, say experts.
“It typically strikes people in their 50s and progresses twice as fast as Alzheimer’s,” said Arkuda’s CEO and cofounder, Gerhard Koenig, and most patients die within seven years of the appearance of symptoms.
A diagnosis of the disease, he said, is “a very devastating verdict for families. There’s nothing you can do about it yet.”
Arkuda is experimenting with drugs that improve the function of lysosomes, components of cells that it says act like a “digestive system” and remove harmful deposits that can accumulate. Proper lysosomal function is particularly crucial in brain cells, which are supposed to last a lifetime.
People with GRN-related frontotemporal dementia don’t have enough of the proteins that play an important role in how lysosomes function. The biotech has tested several compounds that increased those proteins, including progranulin, in mice, rats, and monkeys, based on an examination of the animals’ spinal fluid. Koenig hopes to begin testing compounds in humans in 2021.
Although this particular form of early-onset dementia is rare, executives said they believe their research could have implications for the development of an effective treatment for Alzheimer’s disease, which many drug companies around the world consider the holy grail.
That form of dementia afflicts about 5.8 million Americans, most of whom are 65 or older, according to the nonprofit Alzheimer’s Association. Efforts to develop a medicine that dramatically slows, halts or reverses the progression of the disease have failed again and again.
“For years, companies have focused their efforts on targeting neurodegenerative disease pathologies such as amyloid beta [plaques] and tau [tangles], with little success,” said Bruce Booth, a partner at Altas Venture who chairs the board of Arkuda. “There is growing scientific evidence showing the critical importance of lysosomes in maintaining neuronal health in FTD as well as in other diseases such as Alzheimer’s and Parkinson’s disease.”
FTD-GRN is among several forms of frontotemporal dementia. Some forms of the disease appear to be inherited, while others don’t, according to the Mayo Clinic, of Rochester, Minn. All told, the various forms affect about 50,000 Americans, making it the most common dementia for people under 60.
Several companies are trying to develop drugs to treat different forms of dementia.