Alex Chen wants to keep teaching and cooking as amyotrophic lateral sclerosis (ALS) weakens his muscles. Could an injection under the skin deliver an experimental drug to the motor neurons that control movement?
Can an injection under the skin deliver a drug to the nerve cells Alex relies on to teach and cook?
Alex is 47 and teaches full time. His ALS Functional Rating Scale score fell from 48 to 32 over 27 months. His breathing capacity is 61% of predicted when lying flat. His gene panel was negative. The proposed molecular defect remains unconfirmed in his case.
Speech matters in the classroom. With substantial right-hand weakness, his remaining grip matters in the kitchen.
Breathing difficulty and time away from teaching make repeated procedures a practical concern. We propose testing an injection under the skin.
BioHacks fictional Alex Chen case file.
Alex still teaches full time, even as his function score has fallen from 48 to 32.
Speech matters in the classroom. His remaining grip matters in the kitchen.
Breathing difficulty and time away from teaching are why we’re exploring an injection under the skin.
Healthy. TAR DNA-binding protein 43 (TDP-43) helps process RNA, the working copy of a gene’s instructions.
The break. When TDP-43 is lost from the nucleus, cells can make a shortened STMN2 message. That reduces stathmin-2, a protein that helps maintain and repair nerve fibers.
The repair. An antisense oligonucleotide (ASO) is a short lab-made strand that binds matching RNA. Masking the faulty site restored full-length STMN2 RNA and improved nerve fiber regrowth in cultured human motor neurons. Baughn et al.
Healthy. TAR DNA-binding protein 43 (TDP-43) helps process RNA, the working copy of a gene’s instructions.
The break. When TDP-43 is lost from the nucleus, cells can make a shortened STMN2 message. That reduces stathmin-2, a protein that helps maintain and repair nerve fibers.
The repair. An antisense oligonucleotide (ASO) is a short lab-made strand that binds matching RNA. Masking the faulty site restored full-length STMN2 RNA and improved nerve fiber regrowth in cultured human motor neurons. Baughn et al.
Inject. We propose an injection under the skin. How much intact drug gets into blood, and how often it would be needed, require testing.
Circulate. The drug is linked to an antibody that binds transferrin receptor 1 (TfR1).
Cross. The receptor can carry bound cargo through barrier cells. We start with one binding arm because a related carrier delivered a different ASO in animals. Barker et al.
Enter. A related carrier mainly reached spinal support cells in a mouse study. Our drug needs to reach motor neurons. Hammond et al.
Correct. The strand must escape the cell’s transport compartments and reach the nucleus to bind STMN2 RNA.
Protect. The goal is to preserve useful nerve connections. RNA correction is the first step we would measure.
Delivery risk. Check intact drug on the far side, barrier leakage and corrected RNA in motor neurons.
Systemic risk. Test absorption and repeat-dose safety, including blood counts, kidney function and immune responses.
Inject. We propose an injection under the skin. How much intact drug gets into blood, and how often it would be needed, require testing.
Circulate. The drug is linked to an antibody that binds transferrin receptor 1 (TfR1).
Cross. The receptor can carry bound cargo through barrier cells. We start with one binding arm because a related carrier delivered a different ASO in animals. Barker et al.
Enter. A related carrier mainly reached spinal support cells in a mouse study. Our drug needs to reach motor neurons. Hammond et al.
Correct. The strand must escape the cell’s transport compartments and reach the nucleus to bind STMN2 RNA.
Protect. The goal is to preserve useful nerve connections. RNA correction is the first step we would measure.
Delivery risk. Check intact drug on the far side, barrier leakage and corrected RNA in motor neurons.
Systemic risk. Test absorption and repeat-dose safety, including blood counts, kidney function and immune responses.
Apply equal amounts of ASO to the blood side of a human vascular barrier model. On the tissue side, use human motor neurons with reduced TDP-43 function.
Include untreated cells as a baseline. Deliver free ASO directly into a separate set of neurons to verify that it can correct RNA when delivery is bypassed.
More full-length STMN2 RNA inside identified motor neurons than with either blood-side control, with intact drug transport, a sound barrier and healthy cells.
If the direct control works and the carrier fails, check where the drug accumulated.
We compare free drug, linked drug and a carrier that cannot bind the receptor.
Direct delivery into separate neurons checks whether the drug works when we bypass delivery.
We advance only if motor neurons make more full-length STMN2 RNA and the cells and barrier stay healthy.
If the drug qualifies for Ontario coverage and the household is eligible, Trillium’s deductible is usually about 4% of after-tax household income. At an assumed CAD $75,000, that’s roughly CAD $3,000 per household per year, plus up to $2 per eligible fill after the deductible. The actual treatment price and Alex’s costs are unknown.
Start with specialist monitoring through an ALS clinic. If an injection under the skin proves safe and practical, study whether it reduces procedure burden and allows follow-up closer to home.
A partner lab would need human cell models, research drug batches and RNA and transport assays. A Canadian trial would require safety data, clinical-grade manufacturing, Health Canada authorization and research ethics approval.
Timelines are planning assumptions. Ontario Trillium Drug Program
If the cell test works, we would measure absorption, distribution and repeat-dose safety before a trial.
For an eligible household, the Trillium example gives a rough three-thousand-dollar deductible. The actual treatment price remains unknown.
Early monitoring would happen through ALS clinics. The injection might make follow-up easier if it proves practical.
A Canadian trial needs regulatory and ethics approval.
Preserve abilities he still uses, such as speaking in class and gripping utensils. The proposal offers a path for research.
Earlier on, more function may have been available to preserve. A trial would need to test whether timing changes outcomes.
For Alex now, the goal is to preserve speech and grip.
At his 2024 stage, there may have been more function to preserve.
Our first milestone is more full-length STMN2 RNA inside motor neurons. If we reach it, the next step is to test whether that repair helps preserve the abilities Alex relies on to teach and cook.
Our first milestone is more full-length STMN2 RNA inside motor neurons. If we reach it, the next step is to test whether that repair helps preserve the abilities Alex relies on to teach and cook.