Despite the urgent need for better and more effective treatments for Alzheimer’s disease, there has not been a new or different treatment approved by the FDA for combating Alzheimer’s in over a decade.
Recently, however, a group of researchers studied the current Alzheimer’s drugs development pipeline. They discovered that there were up to 105 distinct treatments being tested as of 2017. Out of those, about one quarter was already in phase III, which is the final round of testing that is required before the FDA passes its judgment on their efficacy and safety. The following post will discuss the upcoming Alzheimer’s treatments.
- Disease-Modifying Therapies
A big percentage of the drugs being tested are DMTs (Disease-Modifying Therapies). This implies that their primary function is not to combat the disease’s symptoms, but rather, to change the course of the disease in order to improve the long-term outcome. As such, most of these drugs are designed to decrease the production of amyloid in the brain while to reduce the levels of amyloid.
The reason behind this approach is because the amyloid hypothesis is considered to be the most likely explanation for the damaging effects of Alzheimer’s disease.
The hypothesis suggests that a cell membrane protein known as the amyloid precursor protein gets clipped by enzymes, which results in small and toxic amyloid protein fragments called beta-amyloid. These fragments disrupt nerve cell communication, while also clumping together in the brain to form plaques. Those plaques trigger a local inflammatory reaction that kills nerve cells.
- Passive Immunotherapies
These refer to antibody solutions that are intravenously injected into the bloodstream. They are designed to target and eliminate beta-amyloid from both the blood and the brain. These solutions are still researched despite some significant setbacks.
Among the tested solutions, aducanumab is quite unique because it targets more than one type of beta-amyloid. Other significant drugs in this category include gantenerumab and crenezumab.
- BACE Inhibitors
In their efforts to decrease beta-amyloid production, scientists have designed drugs that inhibit the activities of an enzyme known as BACE (beta-amyloid cleaving enzyme). Advancements in drug candidates identifying tools have made it simpler to develop BACE inhibitors which can pass through the blood-brain barrier and decrease amyloid levels in the brain and spinal fluid.
Currently, there are about 10 BACE inhibitors being tested in both phase II and III trials. Researchers continue to be optimistic that the BACE inhibitors’ clinical value shall be showcased. Some of the BACE inhibitors being tested currently include LY3202626, LY3314814, CNP520, verubecestat, among others.
Drugs that can counter disease-causing mechanisms are also under investigation. Nevertheless, there are only a few clinical trials for treatments based on non-amyloid theories. And they include:
The other hallmark of Alzheimer’s disease apart from beta-amyloid plagues are neurofibrillary tangles. These tangles are comprised twisted insoluble fibers found within the brain’s nerve cells. They are primarily made of a protein known as tau. This protein forms part of the structure known as the microtubule. The microtubule assists in transporting nutrients as well as other important substances from one section of a nerve cell to the other. However, tau protein is abnormal when one has Alzheimer’s, which causes the microtubule structures to collapse.
Some of the therapies targeting tau protein pathology include AADvac1, ABBV-8E12, TRx0237, TPI-287, RO7105705, among others.
Proponents of the inflammatory theory of Alzheimer’s disease are investigating anti-inflammatory drugs which include agents like formoterol, telmisartan, probucol, TTP488, among others.
Protecting Brain Cells
There is a certain group of medicines under investigation that is neuroprotective in addition to other functions. Some of these drugs include bryostatin, CPC201, simvastatin, insulin, sargramostim, riluzone, BI409306, and others. The mechanism behind each of these drugs’ actions can be found at www.clinicaltrials.gov
Even though one of the most important objectives is to modify this disease, clinicians and patients are also in dire need of effective symptom-controlling drugs. In the symptomatic agents being tested, some of them are aimed at enhancing cognition while others aim to reduce non-cognitive behavioral symptoms.
The cognitive enhancement agents include drugs with an array of actions different from those in the currently-approved treatments for AD. Enhancing cognition involves improving memory, language, thinking, and judgment.
Some of the medications being studied include ginkgo, riluzole, curcumin, nicotine, and nicotinamide.
- Non-Cognitive Enhancing Agents
Most of the medications under testing for treating non-cognitive behavioral symptoms are drugs that are used to treat other ailments and thus are being repurposed. Non-cognitive behavioral symptoms are such as apathy, sleep disorders, and agitation. As such, some of these drugs include antidepressants, cannabinoids, and anticonvulsants.
In the efforts to overcome the effects of Alzheimer’s disease, medications form just one area of the entire plan. Thus, in addition to clinical drug trials, researchers are also looking at non-medication treatments such as transcranial direct current stimulation, light therapy, acupuncture, transcranial magnetic stimulation, deep brain stimulation, and electroconvulsive therapy.
Special diets are also being looked at as a means of enhancing brain function in individuals suffering from the disease.
Despite the efforts being made to curb the disease, we are still far from weakening the grip that Alzheimer’s has on the aging population. This is because we still cannot explicitly state what causes Alzheimer’s. As such, it remains a matter of debate. Currently, the most widespread theory is the amyloid cascade hypothesis, which blames toxic beta-amyloid proteins for the symptoms of AD. Even though this theory has led to the design of a lot of medications, none of them has proven to be effective at combating the disease.
Moreover, a lot of new medications are tested on animal models. The drawback to this approach is that even though we might get results in animals, they do not always translate into benefits for humans. Additionally, even when a promising drug is identified, human testing and FDA reviews typically take more than a decade to complete. Also, the costs of drug development is so high that it discourages pharmaceutical companies from looking for new Alzheimer’s medications.
As such, the federal government, in addition, other collaborators should provide the appropriate funding that is vital towards AD drug research and development.