DSRD is characterized by a significant and often rapid loss of cognitive, motor, and social abilities in individuals with Down syndrome who had previously achieved stable developmental milestones. It often presents in adolescence or early adulthood. Symptoms can include:
Loss of speech or language skills
Decline in motor abilities
Behavioral changes such as anxiety or withdrawal
Sleep disturbances
Catatonia-like features
The exact cause of DSRD is not well understood, but several factors have been implicated:
Neuroinflammation: Chronic or acute inflammation in the brain might contribute to regression.
Autoimmune dysfunction: Individuals with Down syndrome are at higher risk for autoimmune conditions, which could trigger regression.
Mitochondrial dysfunction: Cellular energy deficits may exacerbate neurological symptoms.
Role of Inflammation
Inflammation is a key area of interest in understanding DSRD. Chronic low-grade inflammation, common in Down syndrome due to overexpression of certain genes (e.g., those on chromosome 21 like SOD1), may predispose individuals to neurological disorders. Markers of neuroinflammation, such as elevated cytokines and microglial activation, are often observed in these patients.
Inflammation can disrupt:
Synaptic plasticity
Neurotransmitter function
Neural connectivity
Ketogenic Diet and Inflammation
The ketogenic diet (KD) is a high-fat, low-carbohydrate diet known to induce ketosis—a metabolic state where ketone bodies serve as the primary energy source. KD has shown promise in reducing neuroinflammation and supporting neurological function in several contexts, including:
Epilepsy: KD is a well-established treatment for drug-resistant epilepsy, reducing seizures and inflammation.
Neurodegenerative diseases: KD may mitigate inflammatory processes in conditions like Alzheimer's and Parkinson's diseases.
Autism spectrum disorder: Preliminary studies suggest KD can improve behavior and cognitive function, potentially by modulating inflammation and oxidative stress.
Mechanisms by Which KD May Benefit DSRD
Anti-inflammatory Effects: KD reduces pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α and increases anti-inflammatory mediators.
Improved Mitochondrial Function: Ketones enhance mitochondrial efficiency and reduce oxidative stress, which could alleviate energy deficits seen in DSRD.
Neuroprotective Effects: KD supports the production of brain-derived neurotrophic factor (BDNF), which promotes neuronal survival and plasticity.
Clinical Considerations
Personalization: Not all individuals with DSRD may respond to KD, and some may experience side effects like constipation or nutrient deficiencies.
Monitoring: Ketogenic diets require close supervision, especially in individuals with pre-existing health conditions, to ensure safety and effectiveness.
Adjunctive Therapies: KD may complement other treatments, such as anti-inflammatory medications, behavioral therapies, or immune-modulating strategies.
Dr. Jonathan Santoro’s research:
https://www.chla.org/blog/experts/research-and-breakthroughs/under-microscope-unlocking-mystery-down-syndrome-regression
Jafarpour, S., Banerjee, A.K., Khoshnood, M.M. et al. De novo variants in immune regulatory genes in Down syndrome regression disorder. J Neurol 271, 5567–5576 (2024). https://doi.org/10.1007/s00415-024-12521-y
Share this post