A new Singapore study suggests that patients who carry the gene for neuronal intranuclear inclusion body disease may also present with symptoms of Parkinson’s disease and respond to Parkinson’s disease drugs, which could lead to the development of new drugs for these conditions.
A joint study by the National Neuroscience Institute (NNI) and Singapore General Hospital (SGH) revealed that patients who have been diagnosed with Parkinson’s disease (PD) may have Neuronal intranuclear inclusion body disease (NIID) instead.
NIID is a slowly progressive and disabling neurodegenerative disease which is caused by a mutation in the NOTCH2NLC gene and currently has no effective treatment. Symptoms, which include dementia, Parkinsonism, poor balance, and numbness or weakness in the limbs, vary from patient to patient depending on their age and the progression of the disease. As symptoms worsen over time, older patients usually suffer from the severe form of NIID as the disease progresses to an advanced stage.
The team studied 1000 participants with PD and over 1000 healthy individuals over a period of 15 years, and were surprised to find NIID-causing mutations in those diagnosed with PD. Dr Ma Dongrui, Senior Medical Laboratory Scientist, Department of Neurology, SGH, and first author of the study explained, “To our knowledge, this is the first study reporting PD patients with NOTCH2NLC gene mutations as seen in NIID patients. Thankfully, they responded to PD medications better than most PD patients do. This suggests that there must be factors that can influence why some develop PD while many others develop the more severe form of NIID.” Their results were published in JAMA Neurology.
While analysing the NIID gene, the team found a group of healthy participants who had a “milder” form of mutation. Such mutation in the NIID gene could indicate that they are at risk of developing NIID or PD.
Since NIID can go undetected, a high index of suspicion may be needed even in PD patients. Professor Tan Eng King, Deputy Medical Director and Director of Research, NNI, suggested that, “with what we know now, it might be beneficial for clinicians to be watchful of early cognitive impairment or imaging evidence that may suggest NIID in patients diagnosed with PD. As NIID is caused by a genetic mutation, it also may be worth looking out for family members of PD patients who may show signs of NIID.”
“Our findings suggest that many neurodegenerative diseases overlap and may share a common aetiology. Finding a common link and uncovering the reason why a similar gene mutation leads to both mild PD and a severe form of NIID can help identify new drugs for these conditions.”
Following this study, the team plans to conduct more studies to better understand the mechanism behind NIID and identify new drugs for this condition. More research is needed to understand if the broad clinical phenotype of NIID is related to the subtle genetic differences at the NOTCH2NLC gene locus, race or other factors. Long-term follow-up of carriers of the gene mutation with PD phenotype may provide additional clues. [APBN]