Gene Therapy Trial for ApoE4 Homozygotes
Re: Gene Therapy Trial for ApoE4 Homozygotes
Hi folks, I don't check in here very often, but I did participate in this Lexeo study, so I can tell people what to expect. After extensive testing I ended up getting "rejected" because my spinal levels of amyloid didn't make the cutoff (yay) and I wasn't cognitively impaired enough (yay). (It's a catch-22 because if it is going to help, it has to be done before the damage is done, erk.) The first round was for testing for safety and dosage. Future rounds should be for efficacy. Research is a long slog. Anyway, feel free to contact me if you are thinking of participating so I can tell you what to expect. I was flown to Orlando, so that's the only "site" I know.
Re: Gene Therapy Trial for ApoE4 Homozygotes
Thank you for sharing your great news! Celebrate not being eligible for a trial, because every "screen fail" provides valuable data on the variations among people who are resilient to AD. Your description of the process of first showing safety in Phase 1 trials, and then testing efficacy (clinical benefit) in Phase 2 and 3 is why it's a long slog. Hopefully gene therapies can move forward more rapidly once the Phase 1 trials are complete.Morazan wrote: ↑Mon Dec 16, 2024 10:44 pm Hi folks, I don't check in here very often, but I did participate in this Lexeo study, so I can tell people what to expect. After extensive testing I ended up getting "rejected" because my spinal levels of amyloid didn't make the cutoff (yay) and I wasn't cognitively impaired enough (yay). (It's a catch-22 because if it is going to help, it has to be done before the damage is done, erk.) The first round was for testing for safety and dosage. Future rounds should be for efficacy. Research is a long slog. Anyway, feel free to contact me if you are thinking of participating so I can tell you what to expect. I was flown to Orlando, so that's the only "site" I know.
4/4 and still an optimist!
Re: Gene Therapy Trial for ApoE4 Homozygotes
Seeking Advice on Clinical Trials for Alzheimer's Treatment Options
Hello, everyone.
I’m a 59-year-old male with APOE 4/4, a positive PET scan, and a diagnosis of Mild Cognitive Impairment (MCI). I’m exploring participation in clinical trials as an alternative to currently approved drugs, given what I’ve read about their limited results and potential side effects for people with APOE 4/4 like me.
Currently, I’m considering the following trials:
Lexeo Therapeutics: Unfortunately, I reached out and was informed that their trial is already closed.
Alzheon (Valiltramiprosate): I’ve emailed them but have not received a response yet.
Annovis Bio (Buntanetap): They are expected to provide location details for a trial site closer to me by January 20th.
I’d like to hear your thoughts: Do you think participating in one of these studies is a good option? If so, which one might be the best fit? Or should I be looking in an entirely new direction?
For context, I am on a ketogenic diet, exercise regularly, and am proactive about managing my health. Below are some key biomarker results:
Amyloid Beta 1-42: 244 pg/mL (High; reference range 8.12 - 29)
Total Tau Proteins (t-tau): 343 pg/mL (High; reference range 9.26 - 23.66)
Total Phosphorylated Tau Proteins (tp-tau): 258 pg/mL (High; reference range 1 - 10)
Total Phosphorylated Tau / Amyloid Beta 1-42 Ratio: 1.06 pg/mL (High; reference range <0.028)
I’ve never posted on a chat board before, so I’m unsure how it works. If I’m missing any details or should phrase this differently, please feel free to let me know.
If anyone has insights into these trials, these biomarkers, or other potential directions I should explore, I would deeply appreciate your input. Personal experiences, professional opinions, or knowledge of these approaches would mean a lot to me as I navigate this decision.
Thank you in advance for your help!
Hello, everyone.
I’m a 59-year-old male with APOE 4/4, a positive PET scan, and a diagnosis of Mild Cognitive Impairment (MCI). I’m exploring participation in clinical trials as an alternative to currently approved drugs, given what I’ve read about their limited results and potential side effects for people with APOE 4/4 like me.
Currently, I’m considering the following trials:
Lexeo Therapeutics: Unfortunately, I reached out and was informed that their trial is already closed.
Alzheon (Valiltramiprosate): I’ve emailed them but have not received a response yet.
Annovis Bio (Buntanetap): They are expected to provide location details for a trial site closer to me by January 20th.
I’d like to hear your thoughts: Do you think participating in one of these studies is a good option? If so, which one might be the best fit? Or should I be looking in an entirely new direction?
For context, I am on a ketogenic diet, exercise regularly, and am proactive about managing my health. Below are some key biomarker results:
Amyloid Beta 1-42: 244 pg/mL (High; reference range 8.12 - 29)
Total Tau Proteins (t-tau): 343 pg/mL (High; reference range 9.26 - 23.66)
Total Phosphorylated Tau Proteins (tp-tau): 258 pg/mL (High; reference range 1 - 10)
Total Phosphorylated Tau / Amyloid Beta 1-42 Ratio: 1.06 pg/mL (High; reference range <0.028)
I’ve never posted on a chat board before, so I’m unsure how it works. If I’m missing any details or should phrase this differently, please feel free to let me know.
If anyone has insights into these trials, these biomarkers, or other potential directions I should explore, I would deeply appreciate your input. Personal experiences, professional opinions, or knowledge of these approaches would mean a lot to me as I navigate this decision.
Thank you in advance for your help!
-
- Support Team Intern
- Posts: 71
- Joined: Fri Jul 19, 2024 1:47 pm
- Location: Vancouver, BC
Re: Gene Therapy Trial for ApoE4 Homozygotes
Hi Mark,markh@wcrimail.com wrote: ↑Thu Jan 02, 2025 11:42 am Seeking Advice on Clinical Trials for Alzheimer's Treatment Options
Hello, everyone.
I’m a 59-year-old male with APOE 4/4, a positive PET scan, and a diagnosis of Mild Cognitive Impairment (MCI). I’m exploring participation in clinical trials as an alternative to currently approved drugs, given what I’ve read about their limited results and potential side effects for people with APOE 4/4 like me.
Currently, I’m considering the following trials:
Lexeo Therapeutics: Unfortunately, I reached out and was informed that their trial is already closed.
Alzheon (Valiltramiprosate): I’ve emailed them but have not received a response yet.
Annovis Bio (Buntanetap): They are expected to provide location details for a trial site closer to me by January 20th.
I’d like to hear your thoughts: Do you think participating in one of these studies is a good option? If so, which one might be the best fit? Or should I be looking in an entirely new direction?
For context, I am on a ketogenic diet, exercise regularly, and am proactive about managing my health. Below are some key biomarker results:
Amyloid Beta 1-42: 244 pg/mL (High; reference range 8.12 - 29)
Total Tau Proteins (t-tau): 343 pg/mL (High; reference range 9.26 - 23.66)
Total Phosphorylated Tau Proteins (tp-tau): 258 pg/mL (High; reference range 1 - 10)
Total Phosphorylated Tau / Amyloid Beta 1-42 Ratio: 1.06 pg/mL (High; reference range <0.028)
I’ve never posted on a chat board before, so I’m unsure how it works. If I’m missing any details or should phrase this differently, please feel free to let me know.
If anyone has insights into these trials, these biomarkers, or other potential directions I should explore, I would deeply appreciate your input. Personal experiences, professional opinions, or knowledge of these approaches would mean a lot to me as I navigate this decision.
Thank you in advance for your help!
Happy New Year! I am a member of the support team at apoe4.info and I first want to welcome you here. I think you will find the site to be both an informative resource and a supportive community and I am so glad you found it and have reached out.
Thank you for sharing some of your story. You are clearly a seeker of knowledge and, perhaps more importantly you are putting what you learn about lifestyle factors and Alzheimer's disease into action with your ketogenetic diet and active lifestyle. This on its own can delay onset and mitigate severity, as evidenced by the experience of many members of this forum.
You mention that you have some MCI and I want to reassure you that many men and women who contribute here continue to have active, purposeful lives with MCI. Because it tends to affect only some areas, such as certain types of memory, it really can be helped with modern technology and the support of family and friends.
On the subject of clinical trials, many members have knowledge to share and will no doubt respond to your post. For example, my colleague Nancy "NF52" is currently in a trial of lecanemab and plans to reply with more information about the trials you are considering and how to join a trial as a partner, not a patient. She can also enlighten you on the process of screening for a trial, which can be lengthy, usually providing time to decide if the trial is right for you.
In the meantime, there is much to explore here on apoe4.info. Since you are well versed, some of it might be review, but a great place to start is the Primer , which is a detailed and informative resource written by a practicing M.D. with ApoE4/4.
You can also browse a wealth of information in the Wiki , while the How-To Guide includes topics such as navigating the forum, private messaging, and searching. If you are new to posting on a forum, this might provide some helpful guidance. One great tip is using the quote (") button when replying to a post. Using the button will automatically alert the member of your response.
You can read about other members' experiences and post your own on Our Stories. You may find members describe their clinical trial experiences in their stories.
While exploring the site, you will find a wealth of information about ways other people with ApoE 4/4 are leading their best possible lives, harnessing nutrition, social connection, mindfulness, sleep, exercise, stress management and other strategies to work in their favour.
Keep doing what you are doing and seeking new information and you too will have the best possible outcome. I hope you get the information and support you need from this community. Please reach out if you have any questions and someone will be pleased to help you. Wishing you health and happiness in 2025,
Andrea
Re: Gene Therapy Trial for ApoE4 Homozygotes
"Thanks, Andrea, for the kind and insightful reply! It’s wonderful to find a place where people are so knowledgeable and willing to share their experiences and advice. I really appreciate your help—it means a lot as I navigate these decisions.
"
Re: Gene Therapy Trial for ApoE4 Homozygotes
Hi Mark,Markne wrote: ↑Thu Jan 02, 2025 11:42 am Seeking Advice on Clinical Trials for Alzheimer's Treatment Options
Hello, everyone.
I’m a 59-year-old male with APOE 4/4, a positive PET scan, and a diagnosis of Mild Cognitive Impairment (MCI). I’m exploring participation in clinical trials as an alternative to currently approved drugs, given what I’ve read about their limited results and potential side effects for people with APOE 4/4 like me.
Currently, I’m considering the following trials:
Lexeo Therapeutics: Unfortunately, I reached out and was informed that their trial is already closed.
Alzheon (Valiltramiprosate): I’ve emailed them but have not received a response yet.
Annovis Bio (Buntanetap): They are expected to provide location details for a trial site closer to me by January 20th.
I’d like to hear your thoughts: Do you think participating in one of these studies is a good option? If so, which one might be the best fit? Or should I be looking in an entirely new direction?...
If anyone has insights into these trials, these biomarkers, or other potential directions I should explore, I would deeply appreciate your input. Personal experiences, professional opinions, or knowledge of these approaches would mean a lot to me as I navigate this decision.
Thank you in advance for your help!
I'm so glad you posted about your experience, your diagnosis and your willingness to consider clinical trials. I'm a 72 year old with ApoE 4/4 and have been a clinical trial participant off and on (mostly on) since 2017. For me, being in two trials, one that ended early in 2019 and the AHEAD-45 trial of lecanemab for people with elevated amyloid and normal cognition for the last three years has been empowering and relatively easy. Even with biweekly infusions for the first two years, I continued to be able to go on vacations, keep up with projects and activities and even travel overseas twice in 2023. I have come to feel that being in a trial means my cognitive, physical and brain health are closely monitored by people whom I deeply trust.
Lexeo Therapeutics This was a small gene therapy trial and as you noted it is now complete. My assumption is that Lexeo is seeking investors and/or NIA (National Institute on Aging) funding for a larger trial, but that may take some time. Here's a graphic of how gene therapy is delivered to target cell using a non-virulent "vector". I've seen a catchier term for this idea in a recent conference: "brain shuttle" Alzheon (Valiltramiprosate) In trials, this drug is called ALZ-801. Their completed Phase 3 trial with participants having MCI and mild AD is now in the open-label extension (OLE) phase, which is probably why you haven't heard back from them. Typically the OLE allows researchers to gain more data on safety and clinical benefit in both people who started from the beginning and now may be taking the drug for an additional 18 months or more, and those who started on the placebo and then switched to being on the drug in the OLE. I hope they will submit data to the FDA for "accelerated approval" based on biomarker reduction of amyloid and tau or full approval based on biomarkers and clinical benefit. Many of us on this forum have been looking for them to start a long-projected trial in people with normal cognition and ApoE 4/4 who have elevated amyloid. Here's an example of that enthusiasm for recent news about funding for a large trial: Alzheon Raises $100 Million to Advance ALZ-801 Development & Commercialization and here's a post I wrote in 2022 about their earlier results: ALZ-801 in ApoE4 IMPROVES cognition, reduces plasma P-tau 52% and amyloid beta monomers in one year
Annovis Bio (Buntanetap) (also called Posiphen) As you noted, this trial is at the stage of selecting locations for study sites and starting patient recruitment. A Double-blind Dual Study Assessing Safety and Efficacy of Buntanetap in Participants with Early AD Here's an excerpt about how butanetap works from the Alzheimer's Drug Discovery Foundation's review by outside neuroscientists:
Buntanetap: Evidence SummaryBuntanetap, also known as posiphen or ANVS401, is an orally available small molecule. It is closely related to phenserine, which has also been investigated for use in dementia; as buntanetap does not
have anticholinesterase activity like phenserine does, buntanetap appears to have more permissive
dosing. Phenserine and buntanetap both reduce protein levels of APP and Aβ in cell and animal models
(Lahiri et al., 2007, Winblad et al., 2016). It is thought that buntanetap achieves this protein reduction
through interacting with the IRE/IRP1 complex of neurotoxic protein transcripts such that protein
translation is suppressed. Buntanetap has been shown to reduce levels of Aβ, αSyn, huntingtin, SOD1,
and TDP-43 in different systems (Chen et al., 2021)
Combination trials may be coming soon in Alzheimer's research, since lecanemab (Leqembi) and donanemab (Kisluna) have both been approved by the FDA and newer anti-tau drugs are in the pipeline that may extend their benefit. Both Lecnamab and Donanemab may soon be available in either easier formats (auto-injection through belly fat, like insulin, rather than an infusion for Leqembi) and titrated (gradual dosing up to full dose) for Kisluna to reduce the incidence of of ARIA-E and ARIA-H.
For what it's worth, I'm wondering if your diagnosis of MCI came from a neurologist who ordered the PET scan and gave you a brief screening test such as the MOCA (Montreal Cognitive Assessment. Given your age, a more thorough assessment by a neuropsychologist of short and long-term recall, visual-spatial memory, free and cued recall of lists, category naming, and questionnaires about changes in activities, hobbies, mood, etc. may be informative. I have a friend who is a neuropsychologist in an academic memory clinic who believes that people can be mis-labeled as MCI if they are tested in a stressful situation, with a family member in the room, or by someone who doesn't first seek to establish rapport and reduce anxiety.
You didn't mention having an MRI, but I think your PCP or neurologist could order that to see if you show pre-existing micro-hemorrhages, which can happen in ApoE 4/4 carriers with no symptoms, or other signs of small vessel disease. if you don't have those, it's possible that you'd have a significantly smaller risk of serious adverse events (major edema or brain bleed) on Leqembi. I have had three "possible" (i.e. so small as to be hard to see on imaging) micro-hemorrhages while in the AHEAD-45 study (and may be on the placebo) but can still plan an 18 day trip to Spain, drive through D.C. traffic to see a new granddaughter, participate in reviews of TBI research and remember shopping lists both in testing and when home!
Please keep us posted, and let us know how you heard of all these trials before they're even recruiting! We're all better for being here on the same quest.
Nancy
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4/4 and still an optimist!
Re: Gene Therapy Trial for ApoE4 Homozygotes
"Hi Nancy,
Thank you so much for your incredibly helpful and detailed response! I truly appreciate the time and care you took to share your experiences and insights.
To address your question, I have had two MRI exams, which showed a small amount of white matter and small vessel disease but thankfully no signs of brain bleeding. Additionally, I’ve undergone three cognitive tests. Across all of them, I performed well in most areas, but my recall of things and images has been consistently poor, which seems to be the main challenge for me right now.
Your journey as a clinical trial participant is inspiring, especially the way you’ve managed to stay engaged in life, travel, and contribute to this community while navigating these treatments. It’s encouraging to hear how closely monitored your health has been and how you’ve developed trust in the teams overseeing the trials.
The information you shared about Lexeo, Alzheon, and Annovis Bio trials is fascinating. I’ll be keeping a close eye on the progress of these and hope to see more opportunities for people like us to participate. Your mention of combination trials also gives me hope that we’re on the cusp of even more effective therapies. My hope is I get into the Annovis trial, and, at some point after, I get into a Gene Therapy one.
Regarding your thoughts on neuropsychological testing, I couldn’t agree more. A thorough evaluation that goes beyond a brief screening test can provide so much insight. While my diagnosis of MCI came after consultations with a neurologist and cognitive tests, I might explore more comprehensive neuropsychological testing to gain a fuller picture.
Thank you again for your kind words and the wealth of information. It’s reassuring to connect with someone who has walked a similar path and who generously shares their knowledge to help others. I’ll be sure to keep you and the group updated on my journey and any trials I consider joining.
Warm regards,
Mark
Thank you so much for your incredibly helpful and detailed response! I truly appreciate the time and care you took to share your experiences and insights.
To address your question, I have had two MRI exams, which showed a small amount of white matter and small vessel disease but thankfully no signs of brain bleeding. Additionally, I’ve undergone three cognitive tests. Across all of them, I performed well in most areas, but my recall of things and images has been consistently poor, which seems to be the main challenge for me right now.
Your journey as a clinical trial participant is inspiring, especially the way you’ve managed to stay engaged in life, travel, and contribute to this community while navigating these treatments. It’s encouraging to hear how closely monitored your health has been and how you’ve developed trust in the teams overseeing the trials.
The information you shared about Lexeo, Alzheon, and Annovis Bio trials is fascinating. I’ll be keeping a close eye on the progress of these and hope to see more opportunities for people like us to participate. Your mention of combination trials also gives me hope that we’re on the cusp of even more effective therapies. My hope is I get into the Annovis trial, and, at some point after, I get into a Gene Therapy one.
Regarding your thoughts on neuropsychological testing, I couldn’t agree more. A thorough evaluation that goes beyond a brief screening test can provide so much insight. While my diagnosis of MCI came after consultations with a neurologist and cognitive tests, I might explore more comprehensive neuropsychological testing to gain a fuller picture.
Thank you again for your kind words and the wealth of information. It’s reassuring to connect with someone who has walked a similar path and who generously shares their knowledge to help others. I’ll be sure to keep you and the group updated on my journey and any trials I consider joining.
Warm regards,
Mark
Re: Gene Therapy Trial for ApoE4 Homozygotes
Mark, thank you for your post and Nancy thank you for your very informative response. As for Alz-801, I have been looking for updates often on the APOLLOE4 phase 3 trial as results were supposed to come out in 2024. I was beginning to fear that the results may have not been positive & thats why there have been no updates.
Re: Gene Therapy Trial for ApoE4 Homozygotes
I've wondered about the lack of results also for the ALZ-801 trial. They predicted "last quarter of 2024", so maybe the biostatisticians are poring over every last bit of data to answer a rigorous FDA panel in the new administration. They do have that $100 million for a prevention trial to plan--so let's hope the results are positive!mk3 wrote: ↑Sat Jan 04, 2025 6:54 am Mark, thank you for your post and Nancy thank you for your very informative response. As for Alz-801, I have been looking for updates often on the APOLLOE4 phase 3 trial as results were supposed to come out in 2024. I was beginning to fear that the results may have not been positive & thats why there have been no updates.
4/4 and still an optimist!
Re: Gene Therapy Trial for ApoE4 Homozygotes
Nancy,
i love your optimism, trying to be more like you in 25!
i love your optimism, trying to be more like you in 25!