Welcome to the MNDRA research update. In this report we will highlight outcomes and advances from the MND research world that have caught our attention over the last few weeks.
The NSW Government has awarded $2 million to three outstanding motor neurone disease (MND) researchers, to support people in NSW affected by the disease and to better understand its causes.
The MND Researcher Grants recipients are:
Genetic Associations with an Amyotrophic Lateral Sclerosis Reversal Phenotype
The term “ALS Reversal” describes patients who initially meet diagnostic criteria for ALS who or had clinical features most consistent with progressive muscular atrophy (PMA), but subsequently demonstrated substantial and sustained clinical improvement. Using Professor Rick Bedlack’s database of 22 individuals with documented reversals, the team looked for genetic mutations that correlated with these reversals. They found a significant association between reversals and a mutation in the IGFBP7 gene, which is an inhibitor of the insulin growth factor-1 (IGF-1) receptor that activates the possibly neuroprotective IGF-1 signaling pathway. This finding is limited by the small sample size of 22 individuals but suggests that there may be merit in further exploration of IGF-1 pathway signaling as a therapeutic mechanism for ALS. IGF-1 has been tested previously in MND but perhaps the treatment design could be reconsidered.
Antisense oligonucleotides (ASOs) show potential for treating MND especially where a disease-causing mutation has been identified, such as in the case of tofersen for SOD1 mutations. However, ASOs cannot cross the mammalian blood-brain barrier (BBB), so they need to be injected directly into the spinal cord (intrathecal injection) to access the central nervous system. This process carries risk of infection and can be painful, which presents challenges as this is likely to be administered monthly. These researchers have developed a carrier molecule (human transferrin receptor 1 (TfR1) binding molecule) which can carry ASOs across the blood-brain barrier from the blood meaning ASOs can be injected intravenously (through a standard drip) rather than into the spine. This will make treatment simpler and safer to administer and would not require administration from an expert in intrathecal injections.
Several studies around Brain-Computer Interfaces (BCIs) were reported last month.
Synchron Announces First Use of Apple Vision Pro with a Brain Computer Interface (BCI). The Apple Vision Pro is a computer that is worn on your face but, rather than view the computer’s output through a physical screen, the output is projected directly into your eyes with two small but high-resolution displays a short distance in front of you. The primary user interface is through eye tracking and gestures and users typically control it with eye movements, voice commands and hand gestures. Synchron has been working to make this technology accessible to patients who cannot speak or move their upper limbs through testing a set of “brain gestures” derived directly from the BCI. These “brain gestures” are designed to replace the hand gestures of tap, pinch, scroll, pinch and hold, double tap, triple tap. An example of what can be achieved is shown by a patient who is now unable to lift his arms to paint, so he is learning how to use the Vision Pro to create art. He has also played Solitaire, watched Apple TV, and sent text messages through the brain-controlled device. More information is available here.
Longevity of a Brain–Computer Interface for Amyotrophic Lateral Sclerosis. This report looked at a single patient who had been using an implanted brain–computer interface for 7 years. Frequency of at-home use increased over time to compensate for gradual loss of control of an eye-gaze–tracking device, followed by a progressive decrease in use starting 6 years after implantation. At-home use ended when control of the brain–computer interface became unreliable. Rather than signs of a technical malfunction it appeared that ALS-related neurodegeneration had rendered the patient unable to reliably operate the interface. Although this is only reflecting the experience of one user, it is certainly something to keep in mind as the technology advances with BCIs and they become more common.
An Accurate and Rapidly Calibrating Speech Neuroprosthesis. The question that arises is how useful are BCIs for normal communication? In this study an MND patient received an implanted BCI, and the study focused on how well the patient could communicate over the proceeding 9 months. After just 2 days, 90% accuracy was achieved with a vocabulary of 125,000 words and after 8 months the patient could hold self-paced conversations of approximately 32 words per minute with a 98% accuracy. This shows that conversational communication can be restored after relatively brief training.
