IRAK4 Protein Inhibitor Could Lead to Treatment for Parkinson’s, Other Neuroinflammatory Diseases

A newly discovered inhibitor of the immune protein IRAK4, known as the “master switch” in the development of several diseases, could lead to treatments for autoimmune diseases and neuroinflammatory disorders such as Parkinson’s, according to developer Noxopharm and its majority-owned subsidiary Nyrada.

Pre-clinical studies are ongoing to find the most appropriate therapeutic indications for this discovery. Clinical studies are expected in 2020.

Recent evidence has shown that IRAK4 is a crucial regulator in the body’s innate immune response — the body’s first line of defense — against foreign pathogens and leads to the production of pro-inflammatory molecules called cytokines.

As its abnormal function in innate immune cells is implicated in the development of chronic inflammatory and autoimmune diseases, IRAK4 inhibitors have been regarded as the next generation of anti-inflammatory treatments for autoimmune conditions, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and lupus.

The new compound leads to potent inhibition of IRAK4 and is able to cross the blood-brain barrier and blood-nerve barriers. According to Australia-based Noxopharm, this suggests the new compound could be used to target neuroinflammatory diseases of the central nervous system — such as Parkinson’s, Alzheimer’s, multiple sclerosis, amyotrophic lateral sclerosis — and the body’s peripheral nerves, in particular diabetic peripheral neuropathy.

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The blood brain barrier is a semipermeable membrane that protects the brain against the external environment, and is a major barrier for the efficient delivery of certain therapeutics that need to reach the brain and central nervous system.

“We see our discovery as a breakthrough in providing the tools needed to address inflammatory and autoimmune diseases of the nervous system,” James Bonnar, Nyrada’s vice-president, research & development, said in a press release. Bonnar noted that the development of IRAK4 inhibitors is being pursued in rheumatoid arthritis, gouty arthritis and lupus.

“I see this as a major development,” said Graham Kelly, Noxopharm’s CEO. While noting that it helps Noxopharm evolve into a global biotech company, Kelly added that “at the patient level, it represents a realistic prospect for finally being able to provide treatment for a number of insidious diseases affecting the nervous system, which have defied successful management to date.”

Besides Alzheimer’s, Parkinson’s and multiple sclerosis, Kelly said that neuroinflammation is “associated even with psychiatric conditions such as depression, bipolar disorder and schizophrenia.”

“Having a drug that blocks IRAK4 and all its downstream pro-inflammatory cytokine [signaling] effects, combined with its ability to reach the brain in sufficient levels, is an exciting breakthrough that has resulted from a lot of hard work by a team of Australian chemists and scientists,” Kelly added.

U.S. company Nyrada is two-thirds owned by Noxopharm and is responsible for the non-oncology drug development programs, including an anti-inflammatory, a neuroprotectant and a PCSK9 inhibitor compound. Of note, PCSK9 is a protein involved in regulating the amount of cholesterol in the blood.

Noxopharm recently secured a U.S. provisional patent application and a Patent Cooperative Treaty (PCT) patent application.