Scientists have discovered a novel target for Alzheimer’s Disease and the clinical results are astounding

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On January 26, 2018, a 59-page article was published in the International Journal of Molecular Science, detailing a protein called Galectin-3 (Gal-3, Galectin 3), a molecule that can regulate various intercellular interactions and inflammatory responses, and participates in cell growth, proliferation, and differentiation.

This article focuses on the diseases it is involved in. According to the title, there are 40 kinds of diseases from A to Z, so the title of the article is “Galectin-3: One Molecule for an Alphabet of Diseases, from A to Z”.

Although the types of diseases introduced in the article involve many fields such as cancer, cardiovascular, inflammation, viral infection, pain, hematology, etc., and the potential role of Gal-3 in CNS inflammation is mentioned in the introduction of encephalitis, in the end, it is Focuses on viral encephalitis, ignoring its key role in the pathogenesis of Alzheimer’s disease (AD), because the seminal paper [2] that really reveals this role will take 1 year It will be published half a year later, and the confirmatory test results will have to wait another 4 years, which will be done by Truebinding, a biotech company established in 2016.

On December 2, 2022, Dr. Dongxu Sun, the founder and CEO of Truebinding, was invited to participate in the 15th Congress of Clinical Trials in Alzheimer’s Disease (CTAD) and delivered a speech of more than ten minutes, showing the Gal-3 It plays a role in promoting the aggregation of Aβ, p-Tau, Apo-E4 and other proteins into multimers and the formation of amyloid plaques. The deposition of these plaques is the mainstream theory to explain the pathogenesis of Alzheimer’s disease and is widely recognized as the root cause of neurodegenerative changes and cognitive dysfunction underlying the disease.

Subsequently, Dr. Sun introduced the results of Phase 1b/2 clinical trials of TB006, a Gal-3-targeting monoclonal antibody in the Truebinding pipeline, for the treatment of patients with mild to severe Alzheimer’s disease. The results were astounding, TB006 could easily dissolve these disease-causing Gal-3 proteins, and after 36 days of treatment, 25.4% of patients achieved a response (CDR-SB score decreased by 1 point from baseline), significantly better than placebo 9.7% (p=0.016), and the safety is good.

At the end of the report, Dr. Sun said that TB006 reduced the CDR-SB score by 0.44 more than the placebo in only one month. This is a lot of amyloid-targeted drugs, and 24 months of treatment may not be enough. achievable, this proof-of-concept trial demonstrates that Galectin-3 is an excellent target for the treatment of Alzheimer’s disease.

The response rate of TB006 is very high, and 70% of the patients have experienced disease reversal or stable disease in more than three months, I believe a 100% response rate is possible with 6 months of treatment. Dongxu, Sun, Ph.D., Truebinding

Perhaps because of the time relationship, or perhaps for other reasons, Dr. Sun did not introduce all the details of the trial at the meeting. In a later interview, Dr. Sun revealed more exciting results to us.

Among the subjects, at least one patient with moderate or above Alzheimer’s disease has completely recovered to the level of normal people, and several other patients have basically recovered to the level of normal people. There are quite a few patients with advanced cognitive and life The ability has also been greatly improved.

The significance of TB006 is not only that it is a potential new anti-Alzheimer’s disease drug, but also that it subverts the traditional understanding of the disease.

Alzheimer’s disease is a neurodegenerative disease. In the past, we thought that its disease process was difficult to reverse, because in the process of amyloid deposition forming plaques and neurofibrillary tangles, it will produce toxicity and cause a large number of neuron cells to die , and the neurons in the brain are non-renewable, one dies and one less.

The result of this is that the neurons in the brain are like wood eroded by termites or mechanical parts that have been used for a long time. The damage is irreversible. Delay the progression of the disease, slow down the decline of cognitive function, but the lost memory can’t be retrieved no matter what.

But this may not be the case. ” The neurons of these patients did not die, most of them did not disappear, and most of them are still there. It is just that the neurons in the disease state cannot work and cannot play a role.” Dr. Sun explained.

In other words, the function of these neurons was “disturbed” by amyloid plaques and neurofibrillary tangles, and the reason for the “interference” had a lot to do with the overexpression of Gal-3. If plaques or tangles are compared to a building, Gal-3 acts like cement, which can pour “causative factors” such as amyloid and nerve fibers to form a very strong building, which in turn causes neurons to fail . Play a role.

In the past, the idea of ​​drug research and development was to start with these “buildings”. No matter which aggregation stage is targeted, no matter whether the tool is a “sledgehammer” or an “electric drill”, it is difficult to effectively remove these solid buildings, and it will inevitably damage adjacent health. tissues and neurons. This is also the reason why drugs targeting amyloid plaques in the past inevitably had great side effects. No matter how good the specificity is, what they do is “rough work”.

As a monoclonal antibody drug targeting Gal-3, TB006 can reverse the progress of Alzheimer’s disease by blocking Gal-3, and can skillfully melt the cement in the “building” and remove it without harming other cells. Restoring the function of the “disturbed” neurons.

During the progress of the phase 1b/2 trial of TB006, Dr. Sun’s team received a letter from the family of a patient from Washington, DC, who had progressed to moderate Alzheimer’s disease and forgot his wife’s name. “I also forgot my daughter’s phone number, feared driving, and couldn’t do without my wife’s care in every aspect of life”, he wrote.

However, after receiving TB006 infusion treatment, before leaving the hospital, he called out his wife’s name and called his daughter. The wife was amazed by the efficacy of the drug and wrote a special letter to express her gratitude to Dr. Sun’s team.

The next day she wrote another letter about going to the supermarket to buy groceries, her husband could remember what was missing at home and what to buy, he was no longer afraid of driving, he was able to take care of his grandchildren independently, he was able to walk his dog, he could do biking … “These are all very specific functional improvements and not individual cases” Dr. Sun added. These behaviors are common to ordinary people, and some people even feel tired, but for the family members of Alzheimer’s disease patients with moderate or above, hearing the patient say the familiar but long-lost name again can make them feel happy.

Giving “Despair” the “Hope”

The development of a drug like TB006 has also brought a lot of influence to Truebinding and Dr. Dongxu Sun. After the clinical results were disclosed in October 2022, Truebinding received an invitation immediately. By the end of November, it will be held at the Clinical Trials Conference on Alzheimer’s Disease (CTAD) Share at the conference.

Another very important industry conference in this field will be held in Gothenburg, Sweden on March 28, 2023. Namely: International Conference on Alzheimer and Parkinson and Related Neurological Diseases (AD/PD 2023). “Originally, we missed the time because the deadline for material submission was September, and our clinical results came out in October, but then the chairman of the conference contacted us specifically, hoping to make a report at the conference and share the clinical results of TB006. “Dr. Sun is quite proud.

In addition to invitations to industry conferences, Truebinding has also attracted the attention of pharmaceutical giants and investors. According to Dr. Sun, at least four or five multinational pharmaceutical giants are interested in TB006, and many of them have been “deeply hurt” by Alzheimer’s disease. There are also many top investment institutions in the industry who expressed their hope to bring such good medicine to the market together.

Alzheimer’s disease has become a global crisis and a major public health problem. According to a report released by the World Health Organization in 2018, there are about 50 million Alzheimer’s patients worldwide, and this number will rise to 82 million by 2030, and a staggering 152 million by 2050. In contrast, in 2018, the global cost of dealing with Alzheimer’s disease reached 1 trillion US dollars, which is equal to the combined GDP of Beijing and Shanghai in that year, and this cost will double by 2030.

This disease does not pick anyone, whether it is the president of the United States, a genius writer, or ordinary people, all are at risk of getting sick. There will be many patients who realize that they have Alzheimer’s disease at an early stage, but because “dementia” is too deeply rooted in the hearts of the people, both the early patients and their family members can only be accompanied by despair.

American painter William Uttermoren was diagnosed with Alzheimer’s disease in 1995. He decided to fight against it with the paintbrush in his hand and insisted on painting a self-portrait every year. In that era when little was known about Alzheimer’s disease, he persisted for 5 years, then forgot how to draw, and finally passed away in 2007. His wife said: “Actually, he died the moment he forgot to draw.”

In this desperate environment, TB006 has given hope to many people. The “Washington patient” wants to pass this hope to every patient, telling them that there is a drug that may subvert the disease of Alzheimer’s disease. If the amazing curative effect of TB006 can be verified in the following phase II and III trials, it will undoubtedly become the “blockbuster of the century“, and “Gal-3 inhibitors” will be, together with “insulin” and “PD-1 inhibitors” and other names, engraved on the top of the monument to the history of Modern Medicine.

Salvatore Sciacchitano et al. Galectin-3: One Molecule for an Alphabet of Diseases, from A to Z Int J Mol Sci, 2018 Jan 26;19(2):379. doi: 10.3390/ijms19020379.

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