New SPARK startup, AcureX Therapeutics, gets grant funding

New SPARK startup, AcureX Therapeutics, gets grant funding

Posted on October 1st, 2021

A startup formed out of a SPARK neurology project recently received grant funding from The Silverstein Foundation for Parkinson’s with GBA to support the development of novel, first-in-class drug candidates to treat Parkinson’s disease (PD).

AcureX Therapeutics, founded in 2019, formed from Dr. Xinnan Wang’s SPARK project that identified the cause of a mitophagy defect present in Parkinson’s disease patients with both familial and sporadic forms of the disease. Since this initial discovery, Dr. Wang and AcureX Therapeutics has built a drug discovery platform and a novel PD biomarker to accelerate drug development and de-risk clinical trials.

Dr. Wang’s lab at Stanford focuses on mitochondrial dysfunction in neurological disorders. In 2016, her research found a connection between Miro1, a protein involved in mitochondrial transport, and a commonly mutated protein in Parkinson’s disease – LRRK2. Her research had previously linked PINK1 and Parkin – proteins whose mutations cause PD – to regulation of Miro1. Dr. Wang said in 2016, “In Parkinson’s patients’ cells, Miro is stuck to mitochondria, so damaged mitochondria can’t be removed.”

“Normally LRRK2 attaches to Miro and removes it from damaged mitochondria, similar to how PINK1 and Parkin remove it. When LRRK2 is mutated, it can’t do this job.” Dr. Wang’s team found the impairment in Miro1 removal is present in 95% of PD patients harboring mutations in LRRK2, PINK1, or Parkin, as well as in sporadic PD patients with no known mutations.

In 2019, Dr. Wang’s SPARK project looked to identify small molecules to treat Parkinson’s disease by targeting Miro1, as well as develop Miro as a biomarker of PD. “We hypothesize that a small molecule that specifically targets Miro1 to reduce its levels on the mitochondrial surface can promote mitophagy and rescue Parkinsonian neurodegeneration.” Following the SPARK team’s discoveries of a Miro1 reducer that rescued neurodegeneration in patient-derived neurons and fly models of PD, AcureX was founded.

The grant from the Silverstein Foundation will enable AcureX to develop small molecules that target Miro1 mediated mitophagy (the selective degradation of mitochondria) for the treatment of PD. AcureX expects to begin Phase I clinical trials for Parkinson’s disease in 2023.

AcureX co-founder and CEO William D. Shrader, PhD, said, “Defects in mitophagy are increasingly recognized as key drivers in multiple diseases. This powerful platform based on ground-breaking research from Dr. Wang’s lab has enabled AcureX to discover new targets and invent novel compounds that rescue mitophagy. In Parkinson’s disease, our first indication, we can effectively stop disease progression in multiple model systems with small molecules hitting our first target.”

Read the full press release from the Silverstein Foundation for Parkinson’s with GBA here.