Beta amyloid is no longer the focus of clinical development AD R&D enters the era of great navigation

When it comes to Alzheimer's disease, people may first think of two hallmarks of the brains of patients with beta amyloid (Aβ) and tau protein
.

They were also the main targets for the development of new drugs

Beta amyloid and tau protein are no longer the focus of clinical development

Beta amyloid and tau protein are no longer the focus of clinical development

The report pointed out that there are currently 118 treatments under investigation in the clinical development stage to change the course of Alzheimer's disease
.

Among these 118 therapies, up to 77% of therapies target innovative targets other than misfolded proteins (Aβ and tau)

▲The types of targets targeted by the treatments under research aimed at changing the course of the disease (data source: reference [1], drawing by WuXi AppTec's content team)

The focus on innovative targets is more obvious in early clinical trials.
According to reports displayed on the ADDF website, in 2017, 2018 and 2021, the proportion of therapies targeting misfolded proteins in phase 1 clinical therapies was 43%.
, 25% and 19%
.

In the early treatment of Alzheimer's disease, the proportion of therapies targeting neuroprotective, inflammatory, genetic and epigenetic targets has increased significantly

A variety of therapies for innovative targets have entered Phase 3 clinical trials

A variety of therapies for innovative targets have entered Phase 3 clinical trials

Many therapies under investigation for these new target types have entered the phase 3 clinical development stage
.

For example, a variety of therapies in phase 3 clinical development in 2021 target mitochondria and metabolic functions

Many patients with Alzheimer's disease develop insulin resistance, and type 2 diabetes is also one of the risk factors for Alzheimer's disease
.

Improving insulin sensitivity is a research and development direction for the treatment of Alzheimer's disease.

Recently, Novo Nordisk also launched a phase 3 clinical trial to evaluate the efficacy of its oral GLP-1 receptor agonist semaglutide in the treatment of patients with early Alzheimer’s disease.
This global clinical trial also Patients will be recruited in China (for details, please refer to WuXi AppTec today's push Article 7)
.

In terms of regulating the activity of nerve synapses, AGB101 developed by AgeneBio is a low-dose anti-epileptic drug
.

In the early stages of Alzheimer's disease, patients with memory-related hippocampal gyrus will have neurological hyperactivity

In terms of reducing inflammation, NE3107 developed by BioVie is an ERK small molecule inhibitor that can inhibit systemic inflammation and reduce insulin resistance.
It is currently being tested in phase 3 clinical trials
.

A variety of research therapies for innovative targets provide the possibility to treat Alzheimer's disease from different perspectives for the aging process
.

However, testing the efficacy of innovative therapies is usually a long process.

The future of Alzheimer's disease treatment development

The future of Alzheimer's disease treatment development

One of the keys is the development of biomarkers
.

Historically, there are relatively few biomarkers related to Alzheimer's disease, mainly Aβ and tau protein deposits in the brain

The progress made in neuroimaging and blood testing of biomarkers can not only subdivide Alzheimer's disease patients into different subtypes, but also help conduct clinical trials to test drugs for different subtypes The curative effect
.
By reading the signals of biomarkers, early clinical trials can be used to evaluate whether the treatment under investigation produces efficacy according to its mechanism of action
.

Another strategy for accelerating drug development is "new use of old drugs"-exploring the efficacy of drugs that have been approved by regulatory agencies or drugs under development for other diseases to treat Alzheimer's disease
.
The report pointed out that 35% of the current clinical research therapies are "old drugs and new use"
.
Since the safety of approved drugs has been confirmed, they can quickly enter clinical trials, shortening the time for drug development
.
For example, recently the team of Professor Huang Yadong from the Gladstone Institute in the United States discovered that a diuretic called bumetanide not only relieves cognitive and learning deficits in animal models, but real-world data also shows that it can cause Alzheimer’s disease.
The risk is reduced by 35%-75%
.

The report pointed out that because the current multiple therapies target different physiological processes, they may constitute a combination therapy to provide patients with better treatment options
.
With the help of more biomarkers, we will usher in an era of individualized treatment based on the characteristics of patients, just like the treatment of cancer
.

The causes of Alzheimer's disease are very complex, which has also frustrated past drug development
.
Fortunately, after years of exploration by scientists, based on the biology of aging, the strategy of developing therapies for a variety of physiological processes that affect the onset of Alzheimer’s disease has become the mainstream of drug development.
In this year’s report, there are a variety of research and development pipelines.
The target is the embodiment of this strategy
.

Note: The original text has been deleted

Reference materials:

Reference materials:

[1] 2021 ALZHEIMER'S CLINICAL TRIALS REPORT.
Retrieved November 9, 2021, from https:// 2021 ALZHEIMER'S CLINICAL TRIALS REPORT.
Retrieved November 9, 2021, from https:// [2] The encouraging progress of diagnostics and data sharing in dementia.
Retrieved November 10, 2021, fromhttps://worlddementiacouncil.
org/global-voices/bill-gates/progress-diagnostics-data

[2] The encouraging progress of diagnostics and data sharing in dementia.
Retrieved November 10, 2021, fromhttps://worlddementiacouncil.
org/global-voices/bill-gates/progress-diagnostics-data

[3] GLP-1 Receptor Agonists.
Retrieved November 10, 2021, from https:// GLP-1 Receptor Agonists.
Retrieved November 10, 2021, from https:// [4] 2017 ALZHEIMER'S CLINICAL TRIALS REPORT.
Retrieved November 10, 2021, from https:// 2017 ALZHEIMER'S CLINICAL TRIALS REPORT.
Retrieved November 10, 2021, from https://