Surgery Godfather

Chapter 2183: Chapter 1432: Can They Merge? (2)

"I... have an idea," his voice was soft, with a strong German accent, "Next to M7’s cage there is a pot of pothos, which I have been taking care of. Last month, when I was away, it almost died. When I came back, I didn’t directly water it, I first trimmed off the dead leaves, and then watered only half the usual amount. Now it’s revived and growing better than before."

Everyone looked at him, unsure of what he was going to say.

"What I mean," Fritz blushed, "is that sometimes help is not about giving more, but giving less, at the right time. Scars are the same way, maybe we don’t need to add any new drugs, just reduce something at a specific time."

Yang Ping looked at him, looked for a long time, and then smiled: "Fritz, you’re right, we need a ’pruning’ strategy, not a ’fertilizing’ strategy."

This metaphor inspired Lina. She re-analyzed the database and found a common feature in all scar modulation schemes effective in the late stage: they do not inhibit TGF-β itself but inhibit a specific molecule downstream of TGF-β, Connective Tissue Growth Factor (CTGF). CTGF begins to rise two weeks after damage, peaks at four weeks, and then maintains high levels. It is responsible for compacting loose scars into dense barriers.

"If we can specifically inhibit CTGF starting from the third week," Lina said excitedly, "we can keep the scars loose and permeable while not interfering with early TGF-β’s protective role."

"Is there an inhibitor available?" Yang Ping asked.

"There’s a small molecule called FG-3019, an anti-CTGF antibody developed by FibroGen. It has been tested in clinical trials for pulmonary fibrosis and renal fibrosis, and the safety data is very good."

"Can we get it?"

Lina checked: "It’s a clinical-grade reagent that requires special channels. Also, using it for spinal cord injury is off-label use."

Yang Ping looked at Weber’s video window. Weber was silent for a few seconds, then said, "I’ll find a way. I have an old friend at FibroGen."

Three days later, Weber replied with an email, attached was a draft of a Material Transfer Agreement. FibroGen agreed to provide a small quantity of FG-3019 for pre-clinical research, with the condition that it not be used for human trials.

"That’s enough," Yang Ping said, "We’ll first verify it on animals."

The experimental design for FG-3019 was completed by Hans and a Chinese doctor. They argued for a whole week and finally reached a compromise plan: using a three-factor design, original cell activation, exogenous stem cell transplantation, and CTGF inhibition, each factor at two levels, totaling eight groups. The sample size of each group being fifteen mice, a total of one hundred twenty mice.

"This is the largest scale mouse animal experiment in our Institute’s history," Tang Shun said at the start of the experiment meeting, "It will take three months to complete."

"Three months," Yang Ping calculated, "plus data analysis and paper writing, it’ll take at least six months to get results."

"But if we’re right," Manstein said, "this six months is worth the wait."

After the experiment began, the Institute’s atmosphere became tense and oppressive. Every morning, the first thing everyone did after arriving at work was to check the data board in the animal room, looking at each group’s survival rate, weight changes, and behavioral scores. For the first two weeks, there was almost no difference between the eight groups, leaving everyone on edge.

In the third week, changes began to appear.

In the CTGF inhibition groups, whether used alone or in combination, the scar area began to be significantly smaller than the control group. More critically, the texture of these scars was different: immunostaining showed that in the CTGF inhibition groups, the astrocytes were loosely arranged, with increased cell gaps, whereas the control group’s scars were as dense as a board.

In the fourth week, motor function scores began to show differentiation. The performance of the combined treatment + CTGF inhibition group was significantly better than all other groups, about thirty percent higher than the group with simply combined treatment.

In the fifth week, the "jump-up" time point previously observed by Eva, the combined treatment + CTGF inhibition group showed explosive functional recovery. The BMS score jumped from an average of 2.5 points to 4.8 points, close to the normal mouse score of 5.0 points. Even more astonishing was that histological analysis showed that this group’s damaged area had numerous new neurons and axons crossing through the scars, forming a continuous tissue bridge.

"They crossed over," Eva murmured in front of the microscope, "The axons actually crossed through the scars."

She projected the images onto the meeting room’s big screen. Everyone held their breath. The green axon markers appeared as lines extending from the head side of the damage to the tail side, crossing a light blue area, indicating the "softened" scar.

"This is the first time," Weber said in the video, his voice slightly trembling, "someone has allowed axons to cross through a glial scar in adult mammals."

No one spoke in the meeting room. Then, someone started clapping, first sparsely, then more and more fervently. Tang Shun’s eyes were red, Hans was secretly wiping his eyes, Lina was hugging her laptop, smiling like a child. Fritz stood in the corner, not applauding, just looking at those green lines on the screen, softly saying a sentence in German. No one understood, but M7, if present, might have.

Yang Ping sat in his office, spreading out the data from the eight groups on the table, like laying out poker cards. Each chart was a story: some sad, some bland, some filled with hope.

He picked up the histological photo of the combined treatment + CTGF inhibition group, held it up against the lamp for a long time. Those green axon lines, sparkling under the light, like the willow branches of spring, like spider webs after rain, like all fragile but resilient life forms.

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