Warning: Avoid Brain Injury in mAb Clinical Trials.

PHDoc

In 2023, I was in a clinical trial similar to those mentioned in the NY Times article posted here by Crushed. (Alzheimer's drug horror story from the NYT, posted 10/23/2023). I was tested and accepted into the study in January. After taking 5 doses, one injection each week for five weeks, I started getting side effects. I took no more doses after that.

In Feb I had an ocular migraine and hallucination. Three little toddlers in their summer pajamas dancing in and out of my left peripheral vision. This was attributed to brain edema (swelling) on my MRI. I developed brain fog and confusion.

In May I was hospitalized with symptoms of a stroke. Tingling and numbness in my left lip, fingers, and toes. I'd had a transient ischemic attack (TIA), sometimes called a mini-stroke or pre-stroke. Headaches, brain edema, and brain fog continued.

In June I experienced my first seizure and my MRI showed microhemorrhages (bleeding) in my brain. My driver's license was suspended for 8 months. I still get seizures now. They occur at night and are controlled with medication. My doctor noted that "patients who have a stroke followed by a seizure will need to be on lifelong anti-seizure medication."

It wasn't until well into 2024 that my MRIs were finally clear of brain swelling and bleeding.

What I didn't know (and what they didn't tell me) when I entered the study was that I have one APOE-4 gene which is probably why I reacted so strongly to the monoclonal antibody (mAb) drug they gave me. Some trials of mAb drugs exclude people with APOE-4 genes from the study because their risk of brain injury is too high.

If you or your loved one has one or two APOE-4 genes, please do not volunteer for studies testing monoclonal antibody drugs. In my opinion, the risk of brain injury is too high. I would also be cautious about taking the antiamyloid approved drugs (lecanemab and donanemab) without a good hard discussion with your doctor or a neurologist first.

marionwilhelm

Gosh. I have 2 of the APOE genes, discovered from testing for a drug study. I didn't qualify for the study so I guess I'm lucky? I am sorry that you had such a dreadful reaction.

PHDoc

Thank you. You may not have qualified because you have those 2 genes and they knew it was too dangerous for you to be in that trial. Be thankful you were not allowed into the study. Other studies not testing mAbs would be better for you.

LBC83

https://alzconnected.org/discussion/71415/warning-avoid-brain-injury-in-mab-clinical-trials

Thank you for your posting. You are a brave individual, volunteering for a clinical trial.

I've completed my 12th Leqembi infusion, my final MRI will be after my 13th infusion on Monday. I've had zippo reactions from the Leqembi / infusions.

Prior to starting Leqembi, I carefully studied the Phase 3 Leqembi drug trial paper published in the New England Journal of Medicine (link below). I'm an APOE4 heterozygote (one gene). For this group, 10.9% of the total participants in the Leqembi Phase 3 trial experienced ARIA-E, vs 1.9% on placebo. For APEO4 homozygote (two genes), 32.6% of the participants experienced ARIA-E, vs 3.8% on placebo. I believe these numbers are based on test results identifying ARIA-E. They also separately reported symptomatic ARIA-E, only 1.7% of APOE4 heterozygote's apparently experienced symptoms of ARIA-E, and 9.2% of APOE4 homozygotes experienced symptoms of ARIA-H.

Given my family history (both my parents had dementia), and after watching my Mom slowly fade away from the disease, and given I have only one of the two dreaded genes, after talking this over with my neurologist and my wife, I elected to start Leqembi. I am glad I made that decision, as I feel it is buying me more quality time with my family, albeit with a slight risk for ARIA. There is also a risk I will die in a fatal car accident on my way to the gym, or get shot walking around my city, or get cancer. Life is full of risks, I judged that the incremental risk from Leqembi was low. But I respect that others might come to a different conclusion.

Finally, I remain hopeful that in the next couple of years, drugs which address tau that are currently or will soon start clinical trials will prove successful, be authorized by the FDA, and then can be added to my arsenal.

Here is a link to the Leqembi Phase 3 trial
https://www.nejm.org/doi/full/10.1056/NEJMoa2212948