Discussion and Writing Collaboration;
Dr. Kinal Bhatt, MPH, and Tea Romero, MBA
Dr. Kinal Bhatt, a regional medical director at Life Molecular Imaging (LMI), is an MD, MPH with about 8+ years of clinical research experience in various therapeutic areas. LMI strives to develop novel PET tracers to improve the early detection and characterization of chronic and life-threatening diseases, leading to better therapeutic outcomes and improved quality of life.
Dr. Bhatt’s focus is on Neurology, particularly Alzheimer’s disease (AD). She also researches other amyloid protein and tau protein-related pathologies. Both proteins are key hallmarks of AD diagnosis.
LMI is in a unique position to have an FDA-approved (F18)Neuraceq. LMI also has tau tracer (F18)PI-2620 that is currently in phase 2 and planning for a future phase III trial. The pipeline is also quite diverse including (F18)F-DED and (F18) alpha-synuclein in pre-clinical phases, (F18)GP-1 in phase 2 for thromboembolism, in phase 2 (68)Gallium, and (177)Lutetium for prostate and breast cancers, and (F18)FSPG for lung cancer, HCC, and IBD.
Alzheimer’s disrupts the brain’s processes vital to neurons and their networks, including communication, metabolism, and repair. Tens of billions of neurons in the human brain process and transmit information via electrical and chemical signals, Typically, what people most commonly associate with AD is shrinkage of the brain or brain atrophy. However, the brain typically shrinks to some degree in healthy aging, but surprisingly, does not lose neurons in large numbers. In AD, however, the damage is widespread, as many neurons stop functioning, lose connections with other neurons, and die.
AD affects cognitive function over time and the disease leads to various health complications. Individuals in the preclinical disease phase are unlikely to be aware of changes occurring when the cognitive function is not yet affected but can progress to mild cognitive impairment (MCI) or Dementia. MCI due to AD phase patients may have very mild symptoms that do not affect everyday activities. Dementia due to AD is further broken down into the stages of mild, moderate, and severe, which reflect the degree to which symptoms interfere with one’s ability to carry out everyday activities. Various issues can cause symptoms like those seen in AD from memory loss, trouble with words in speaking or writing, confusion about time and space, changes in mood or personality, etc.
Common comorbidities include depression/stress/anxiety, blood flow disruption to the brain, infection, thyroid problems, vitamin deficiency, sleep apnea, alcohol, and prescription side effects. Therefore, clinicians need accurate ways to diagnose what is causing memory loss and whether a patient has memory loss due to Alzheimer’s disease.
Accurate diagnosis is possible based on current technologies. In addition, the clinicians evaluate various physical, neurological, and cognitive exams. Clinicians can order blood work to rule out some of the other causes of memory loss earlier discussed – such as vitamin deficiency, thyroid, kidney, or liver diseases.
The clinician can do an invasive procedure such as lumbar puncture to obtain cerebrospinal fluid to measure proteins involved in AD pathologies, such as Amyloid and Tau. Also, clinicians have non-invasive imaging biomarkers for amyloid and tau protein using PET imaging. New technologies available only since 2018, allow the Physicians and Scientists to see the amyloid and tau antemortem. Pre-2018 scientists could only access the amyloid and tau postmortem.
The last FDA-approved drug to treat AD symptoms was approved in 2003. After more than 200 research projects in the last decade have failed or have been abandoned. In June 2021 FDA provided the accelerated approval of Biogen’s Aduhelm. According to the FDA website, Aduhelm is a first-of-its-kind treatment. First approved therapy that targets the pathology of AD. Until the approval of Aduhelm, there have been five FDA-approved treatments targeting symptoms of AD: Rivastigmine, Galantamine, Donepezil, Memantine and Memantine combined with donepezil. Please note none of the pharmacologic treatments available slow or stop the damage and destruction of neurons that cause AD symptoms and make the disease fatal.
Aduhelm is the first AD drug that has been shown through clinical trials to remove amyloid from the brain over time. There is an ongoing post-marketing trial targeting efficacy of Aduhelm with results anticipated in 2030.
There is reason to feel optimistic, there are several other drugs of similar mechanism currently in late-stage trials. There is a different anti-amyloid treatment that is anticipating accelerated approval by the summer of 2022 and there are 2 other medications in phase III currently.
Dr. Bhatt recommends the following book to learn more about Alzheimer’s Disease, The Problem of Alzheimer’s by Dr. Jason Karlawish.