Nasal Drugs Could Slow Parkinson’s Disease Progression

New research indicates that blocking proteins with medications inhaled through the nose may be a useful therapeutic approach in Parkinson’s disease and other conditions characterized by alpha-synuclein aggregates.

Alpha-synuclein aggregates are known to spread in the brain, and are thought to drive brain cell death in patients with Parkinson’s, Lewy body dementia and multiple system atrophy. However, the mechanisms that drive this spread are not understood. According to “Selective targeting of the TLR2/MyD88/NF-κB pathway reduces α-synuclein spreading in vitro and in vivo,” published in Nature Communications, the spread of alpha-synuclein aggregates in the brain is dependent on a protein receptor called TLR2 and a transcription factor called NF-KB.

“Currently, there are no treatments that slow the progression of Parkinson’s disease – they only treat the symptoms,” said Kalipada Pahan, PhD, the Floyd A. Davis Professor of Neurology at Rush University Medical Center and a research career scientist at the Jesse Brown VA Medical Center, who led the study. “Understanding how these diseases work is important to developing effective drugs that inhibit alpha-synuclein pathology, protect the brain, and stop the progression of Lewy body diseases.”

The lab-developed peptides tested in the study are known as TLR2-interacting domain of Myd88 (TIDM) and NEMO-binding domain (NBD). The drugs, which were delivered through the nose, were found to slow inflammation in the brain and stop the spread of alpha-synuclein in mice with Parkinson’s disease. The treatments also improved the mice’s gait, balance, and other motor functions. These results suggest that blocking TLR2 and/or NK-KB may prevent the spread of alpha-synuclein in the brain.

“If these results can be replicated in patients, it would be a remarkable advance in the treatment of devastating neurological disorders,” Dr. Pahan says.

The research was supported by funding from the National Institutes of Health. Other authors of the article are Debashis Dutta, PhD; Malabendu Jana, PhD; Moumita Majumder, PhD; Susanta Mondal, PhD; and Avik Roy, PhD, all from Rush University Medical Center.