Therapeutic developments for neurodegenerative GM1 gangliosidosis.

GM1 gangliosidosis (GM1) is a rare but fatal neurodegenerative disease caused by dysfunction or lack of production of lysosomal enzyme, ß-galactosidase, leading to accumulation of substrates. The most promising treatments for GM1, include enzyme replacement therapy (ERT), substrate reduction therapy (SRT), stem cell therapy and gene editing. However, effectiveness is limited for neuropathic GM1 due to the restrictive nature of the blood-brain barrier (BBB). ERT and SRT alleviate substrate accumulation through exogenous supplementation over the patient's lifetime, while gene editing could be curative, fixing the causative gene, GLB1, to enable endogenous enzyme activity. Stem cell therapy can be a combination of both, with ex vivo gene editing of cells to cause the production of enzymes. These approaches require special considerations for brain delivery, which has led to novel formulations. A few therapeutic interventions have progressed to early-phase clinical trials, presenting a bright outlook for improved clinical management for GM1.

Treating Severe Traumatic Brain Injury: Combining Neurofeedback and Hyperbaric Oxygen Therapy in a Single Case Study.

In 2014, a 26-year-old male was involved in a motor vehicle accident resulting in a severe traumatic brain injury (TBI). The patient sustained a closed-head left temporal injury with coup contrecoup impact to the frontal region. The patient underwent a left side craniotomy and was comatose for 26 days. After gaining consciousness, he was discharged to a brain injury treatment center that worked with physical, speech, and occupational issues. He was discharged after eight months with significant speech, ambulation, spasticity, and cognitive issues as well as the onset of posttraumatic epilepsy. His parents sought hyperbaric oxygen treatment (HBOT) from a doctor in Louisiana. After 165 dives, the HBOT doctor recommended an addition of neurofeedback (NFB) therapy. In March 2019 the patient started NFB therapy intermixed with HBOT. The combination of NFB and HBOT improved plasticity and functionality in the areas of injury and the correlated symptoms including short-term memory, personality, language, and executive function, as well as significantly reducing the incidence of seizures. Severe brain injuries often leave lasting deficits with little hope for major recovery and there is a need for further research into long-term, effective neurological treatments for severe brain injuries. These results suggest that HBOT combined with NFB may be a viable option in treating severe brain injuries and should be investigated.