Step into the realm of groundbreaking research led by Dr. Jeffrey T. Apter, President of Global Clinical Trials LLC. Specializing in Central Nervous System (CNS) clinical trials, Dr. Apter, a nationally acclaimed psychopharmacologist, brings his expertise as a senior attending physician at the University Medical Center at Princeton, as well as a Board Member Alzheimer’s NJ, Dr. Apter shares insights in this article, accompanied by his recent publication on Novel Therapies for Alzheimer’s Disease, co-authored with Dr. Kaylee White and Iqra Hasan.
Therapies for Alzheimer’s Disease are rapidly progressing with many new treatments being tested in clinical trials and getting approved each year. This year alone in the United States, there were at least 2 drugs that have been early approved by the FDA: Lecanemab, and Donanemab. These drugs all work to reduce beta amyloid levels in the brain, which have been proven to significantly decrease in various clinical trials. Both of these treatments are intravenous infusions that can be administered monthly, or every two weeks. The duration of treatment can be for years at a time to obtain a sufficient diminishment of amyloid. They fall under the drug class of monoclonal antibodies and are most commonly used for patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease. This is because these drugs are meant to change the progression of disease and delay onset, sometimes as much as 35%. The current line of treatment for Alzheimer’s Disease and dementia typically are medications that only treat the symptoms of disease, instead of targeting the cause. As technological capabilities advance, there are more tools that can help detect susceptibility to Alzheimer’s as well as catching the disease in its early stages. This can be done with tests like the Precivity Assay, which can detect clinically significant levels of amyloid in the blood before memory loss can present as a symptom. With a tool like this, it will be possible to identify patients with a family history of Alzheimer’s disease to seek treatment and attempt to delay the progression of disease with the new treatment options that are becoming increasingly available. With an indication of this nature, preventing progression before pronounced outcomes like memory loss and other neuropsychiatric symptoms can prove to be invaluable. In addition to amyloid antibody therapy, there is also further research that includes anti-tau antibodies, antigens, and vaccines. This is because the amyloid hypothesis has long been the primary mechanistic cause of AD, and in more recent years it has been shown that tau aggregation is what leads to cell damage and neurofibrillary tangles. Current clinical trials testing anti-tau drugs include Janssen JNJ-63733657, a humanized IgG1 monoclonal antibody that binds to aggregated phosphorylated tau. There is also Merck MK2214, which is another humanized monoclonal tau antibody that targets specific parts of pathological tau which is theorized to prevent extracellular spread from neuron to neuron (Merck Sharp & Dohme LLC, 2023). Also in development are anti-inflammatory drugs, such as that of Cassava Sciences, simufilam, which binds to an altered conformation of filamin A, which is related to elevated levels of beta amyloid. The altered filamin A prevents various toxic signaling cascades as seen in the AD brain.
References
- A Study of JNJ-63733657 in Participants with Early Alzheimer’s Disease | Global Trial Finder. (n.d.). Retrieved May 15, 2023, from https://globaltrialfinder.janssen.com/trial/CR108832
- Bhandari, T. (2022, February 22). Blood test for Alzheimer’s highly accurate in large, international study. Washington University School of Medicine in St. Louis. https://medicine.wustl.edu/news/blood-test-for-alzheimers-highly-accurate-in-large-international-study/
- Cassava Sciences’ Simufilam Improves Cognition and Behavior in Alzheimer’s Disease in Interim Analysis of Open-label Study | Cassava Sciences, Inc. (n.d.). Retrieved May 15, 2023, from https://www.cassavasciences.com/news-releases/news-release-details/cassava-sciences-simufilam-improves-cognition-and-behavior
- Kametani, F., & Hasegawa, M. (2018). Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer’s Disease. Frontiers in Neuroscience, 12. https://doi.org/10.3389/fnins.2018.00025
- Lecanemab Approved for Treatment of Early Alzheimer’s Disease. (n.d.). Alzheimer’s Disease and Dementia. Retrieved May 15, 2023, from https://alz.org/alzheimers-dementia/treatments/lecanemab-leqembi
- Lilly’s Donanemab Significantly Slowed Cognitive and Functional Decline in Phase 3 Study of Early Alzheimer’s Disease | Eli Lilly and Company. (n.d.). Retrieved May 15, 2023, from https://investor.lilly.com/news-releases/news-release-details/lillys-donanemab-significantly-slowed-cognitive-and-functional
- Merck Sharp & Dohme LLC. (2023). A Multiple Ascending Dose Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-2214 in Adults With Mild Cognitive Impairment or Mild-to-Moderate Alzheimer’s Disease (Clinical Trial Registration No. NCT05466422). clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT05466422