Casma Therapeutics has launched with $58.5 million in funding from Third Rock Ventures to pursue drugs that can enhance autophagy, the process used to break down and recycle cellular components.
Researchers have long known that cells lasso dysfunctional or aging components into a vesicle that is sent to the lysosome for degradation. But the particulars of that process have only recently come to light.
In 2016, Japanese cell biologist Yoshinori Ohsumi won the Nobel Prize in Physiology or Medicine for his work to tease apart how autophagy works in bacteria. Casma’s scientific founders have built on that research to identify key players in the process in mammalian cells.
Casma will try to translate those insights into drugs that can boost autophagy. The company is first focusing on a collection of rare genetic diseases called lysosomal storage disorders (LSD). People with LSDs are missing an enzyme that breaks down a key protein or peptide, causing a toxic buildup of cellular waste inside the lysosome. Although enzyme replacement therapies exist for a handful of LSDs, their efficacy is limited because they can’t easily reach the brain and spinal cord. And roughly two-thirds of the 70 known LSDs primarily affect the central nervous system, Casma CEO Keith Dionne points out.
The biotech firm hopes to address LSDs by developing molecules that work upstream of the lysosome. Such drugs could potentiallytreat multiple diseases.
The company’s first challenge will be to develop small molecules that act precisely on the self-destruction pathway. Dionne notes that certain classes of drugs, such as mTor inhibitors, are known to induce autophagy, “but they do it as one of 30 or 40 different things.”
In tandem, Casma will need to develop tests to understand whether its drugs are working. “Currently, there are not good biomarkers that show whether or not you’re inducing autophagy,” Dionne says.
The initial focus on LSDs is expected to help Casma tackle more common diseases marked by a buildup of cellular debris. They include neurodegenerative disorders like Parkinson’s disease, muscle myopathies, liver issues, and inflammation.