Emerging evidence suggests that modulating the immune system to decrease inflammation in the nervous system can be a powerful disease-modifying approach for the treatment of Alzheimer’s disease (AD).  This is exemplified by studies showing that the treatment of select AD patients with sargramostim, a recombinant granulocyte-macrophage colony stimulating factor (GM-CSF), reduced AD-related symptoms compared with placebo. Unfortunately, sargramostim is rapidly metabolized and thus requires frequent injections, increasing potential adverse effects and reducing treatment adherence and patient quality of life. To address these issues, we have developed a novel, long-acting, recombinant GM-CSF—PDM608—that should confer the same benefits as sargramostim but require less frequent dosing. A Phase 1 study in healthy volunteers will provide critical information regarding safety, tolerability, and pharmacodynamic effects of PDM608 to inform the design and maximize chances of a successful future trial in AD patients. 

Our initial testing has demonstrated robust and durable expansion of key anti-inflammatory immune cells (regulatory T cells; Tregs) and protection of neurological tissue following administration of PDM608 in neurodegenerative disease animal models relevant to AD. We are currently manufacturing the drug for use in additional FDA investigational new drug (IND) studies and clinical trials, and we are assembling a data package to support evaluation and dosing in humans. These are the critical first steps toward safe testing of PDM608 in humans. 

PDM608 could be transformative for AD treatment by tempering nervous system inflammation and restoring neuronal function. The innovative design of PDM608 reduces predicted host immune responses to the drug and extends the half-life of GM-CSF activity to reduce dosing frequency. This design is expected to enhance patient safety, treatment adherence, and quality of life.