Re: Narsoplimab generally
Well said, Alan. I agree 100%.
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Well said, Alan. I agree 100%.
Thanks for pointing out the date, Bill, I didn't see that. I understand the further comments. Thanks guys.
Apparently OMER has opened up 21 sales positions for narso, so the company is confident, as past statements and the logic of the n=28 with at least 15% survival criteria indicated for quite some time.
Confirmation narso dosing will be according to body weight of the patient (you are unlikely to find all the technical things in the paper comprehensible).
https://ebmt2021.abstractserver.com/pro … tions/1265
"6 weekly IV doses of 4 mg/kg"
70 kg (~150 lb) patient ..... 280 mg dose ...... 0.28 gm ...... smaller than I expected but I had no data to go on.
I have another reference of a woman with GVHD getting 4mg/kg once or twice weekly for a total of 18 doses.
So dose/kg seems constant.
1 or 2 doses a week
6 weeks in your example, 2 to 4 weeks in Bergamo and maybe 10 weeks in the GVHD.
Now go to narso manufacturing of 2,000 or 20,000 litres.
How many mg in a L?
If it is water, 1000 g/L IOW 1g/ml
That is 1Mmg/L
If narso is not the same density of water....
We don't know
2 Billion mg/2000L
But the 2000 or 20,000 liters is not the resulting product. It is the size of the reactor vessel. The end product, as I understand it is less than the capacity, but I don't know how much less.
We could reduce the 2B to 1Bmg/batch and assume the density is about the same as water so that each bath is 1B grams
If the average person gets 250 to 500 mg (0.25g to 0.5g)....
Since I am doing this in my head without a spreadsheet to keep track of the zeros, I'll let Bill and the rest of you play with the numbers. For my taste, we have enough assumptions required that we can't be confident of the answer to the question of
1. how many patients can be treated with the current supply?
2. How much narso inventory is needed to get approved to treat Covid? how about for HSCT-TMA
3. How much is needed for other trials?
4. How much does it cost to make/gram?
5. What's the average number of grams for each patient for each potential indication?
I think the clinicaltrials/gov listing for the various indications should provide the average dose regimen.
The end product, as I understand it is less than the capacity, but I don't know how much less.
My recollection from months ago when I asked my friend in the business ....... low single digit yields are typical .... maybe 4%?
I have not looked back to check nor worked with the new numbers.
Yes, I recall what sounded like an absurdly low yield number mentioned a few months back. This seems to be the key figure of merit.
Spent some time with my bioreactor friend late this afternoon. A few interesting things:
Current best tech setups (bioreactor with internal mixer plus a "skid" containing all the elaborate hardware that handles all the instrumentation and fluid/gas handling involved in each batch) are producing more like 10% yields.
Current bioreactor/skid combos producing pharmaceuticals are typically made from plastic ..... a big bag, say 1000 to 5000 liters and that elaborate skid ...... are disposable. Single use. A bag with its plastic mixer components, alone, goes for over $10,000.
A stainless steel bioreactor/mixer could be $1,000,000. Sterilization specs drive the disposable single use setups.
Neither stainless steel nor plastic can be sterilized adequately/repeatedly for production setups like for vaccines and monoclonal antibodies.
Setups for things like like high volme beverage production have much lower sterilization specs and are commonly and economically made with stainless steel.
So... a guess on how much it costs to make 1 batch of 200L from a 2000L vessel?
Any idea on the weight of a L of the finished product (or do we have to consult a guy from a carnival for that? :>)
no and no, unfortunately.
Interesting, thanks Bill. Let's forget about the stainless steel reactor, because it can't be sterilized to specs. So that leaves the plastic bag. I'm not saying that a heavy-duty plastic bag cannot be constructed, but they're still calling it a plastic bag. Therefore, I can't see that the Narso inside the bag, cooking as it were, can be too much thicker (heavier) than water. The resistance of the product inside the bag would be difficult to overcome in terms of thorough mixing, and also in terms of the plastic bag being able to withstand the forces exerted by the mixing. My guess is that a guess, or estimation, that Narso weighs close to what water weighs, is a good starting point for our purposes until we know what the exact weight is.
I disagree Avi.
IMO we just don't know.
If the bag is filled with components to start with, including some liquids (not necessarily any water... maybe some isotonic saline perhaps) the 'cooked" residue that is the final 200L maybe like heavy sludge that would sink to the bottom because it weighs more or something like the cream fraction of whole milk, which floats on top.
Good point, you could be right.
A few more bioreactor thoughts as I understand them now (subject to revision). Picture them like factories ....... materials go in, products come out.
The big reactor vessel (bag or tank) is preceded by what could be a "train" of skids, starting maybe with a benchtop unit that produces the first batch or stage of something that eventually becomes the goop that fills the production bag/tank. There could be multiple stages in this train, building larger and larger batches until enough is made to fill the big vessel. Its environment is tailored to what's transpiring inside .... temperature, pressure, etc.
Media (food) tailored to the (living) goop's requirements is fed in and the goop biologically produces the desired end product under closely controlled conditions. The goop+media may be very fluid or viscous. Mixers may be simple circulators in the bottom to large, filling the tank with paddles or vanes to mix the contents to meet requirements.
When the process in the vessel is complete (hours/days/weeks), it may be allowed to settle/separate on its own prior to draining. Centrifuges are used to seprate some outputs. Some setups monitor the vessel outflow with chromatography, starting and stopping diverting when the outflow contains the desired end product.
Some bioreactor setups (not pharmaceutical ones) produce substances more like oatmeal up to silly putty consistancy. They get handled differently.
Anyway, the whole process of making the goop, creating its food(media), managing the production cycle and processing a bioreactor's output is quite complicated. Costs per batch can vary from a penny or less per gram (some consumer beverages?) to thousands of $$$ per gram ..... more than gold.
Interesting description of how a biologic is made. I never really thought much about the goop per se.
Thanks Bill. I don't suppose your friend can provide any pictures? Probably proprietary and/or confidential.
And for our financial modeling purposes, not enough specifics... but at least it is clear that we do not know and any guess would be foolhardy without (probably lots more than a degree in biochemistry) specific knowledge about narso (some of which might be in or implied in the wording in the patent.
I don't suppose your friend can provide any pictures? Probably proprietary and/or confidential.
Correct, although below I'm providing some links to stuff I should have looked up long ago to gain insight into this bioreactor field, but didn't until this morning. I can say there's VERY tight security involved in a lot of this for competitive reasons. Proprietary hardware and processes. Even within a given company/laboratory, info can be compartmentalized. My friend is involved with supplying bioreactors and skids (front and back), both stainless and disposable. He learns about what products (categories) will be produced but typically only info found in open literature ...... like company websites and advertising info. We've discussed the breadth of those categories and it's quite wide/diverse. I won't give specifics but some are damned interesting ..... like stuff that isn't commercial yet but may be ..... if the clients are successful ...... within a few years.
Pictures and stuff:
First I Googled "bioreactor bags" (images) and got
That's a long URL but gets you to a scrapbook of relevant stuff. In that set, I clicked on an image labeled "Markets Expand for Single-Use Bioreactors" and got to a site where I could access a full article worth reading if you're into details. It's at:
Does Omeros have anything to fear from ALXN's drugs (Soliris & Ultomiris) in fighting HSCT or any other indication.
ALXN repeatedly has said it will run a trial on HSCT or that it is running trial. As you know both of Alexion's complement drugs shut down normal immunity so that patients who take it may die of infection. That's why the FDA requires a BLACK LBEL WARNING and that patients need to be treated for at least a couple of weeks to boost their immune system before being given Soliris (or equivalent). Not that this sanger is because Alexion's drugs (and all complement companies other than Omeros) target something other than MASP2 and the lectin pathway.
Here is something on Soliris found by a member of the email group I am in:
We report the results of a single-center analysis of a cohort of 39 patients treated between 1997 and 2016 for transplantation-associated thrombotic microangiopathy. We evaluated 2 subgroups of patients: 24 patients treated between 1997 and 2014 who received conventional therapy and 15 patients treated with the complement-inhibiting monoclonal antibody eculizumab between 2014 and 2016. The conventional therapy group was treated predominantly with defibrotide alone or in combination with plasmapheresis or rituximab. Despite an initial response rate of 61%, only 4 patients (16%) were long-term survivors, 2 of whom had a low- risk thrombotic microangiopathy without multiorgan damage. Progression of thrombotic micorangiopathy and bacterial/fungal infections contributed equally to treatment failure. The overall response rate in the eculizumab group was significantly higher, at 93%. In addition, we were able to stop eculizumab treatment in 5 patients (33%), all of whom had high-risk thrombotic microangiopathy, due to sustained recovery. Despite the very good response in the eculizumab-treated group, we did not observe a significant improved overall survival, due primarily to a high rate of infection-related mortality (70%). Therefore, further studies are needed to identify the optimal therapeutic management approach for transplantation-associated thrombotic microangiopathy to improve its dismal outcome.
Received 25 May 2017 Accepted 14 August 2017
Thrombotic microangiopathy Allogeneic stem cell transplantation
That was pretty interesting, Bill. Thanks. I saw where Lonza says the stainless steel tanks are more suited for larger batches, but to me the bottom line is always the bottom line. Would it be less expensive to manufacture smaller doses of Narsoplimab in a coordinated system of smaller plastic bag tanks, compared to a larger (single) batch in a stainless tank? We don't know the answer to that question.
But it does seem as if the need for these bioreactors is well met by industry, what with all the choices of manufactures and different systems thereby. I wonder if this means that Omeros will, one way or another, at some point in time be able to contract for, or manufacture in house, enough Narsoplimab to meet demand.
I wonder if this means that Omeros will, one way or another, at some point in time be able to contract for, or manufacture in house, enough Narsoplimab to meet demand.
Avi, I'm confident that point in time arrived some time ago and it doesn't involve producing commercial quantities of narso in house. My friend says starting up a commercial setup for narso production requires very specialized facilities like Lonza certainly has that have certified sterile rooms, sterile water supplies, trained staffs, etc.
1. Omeros does not pay by the batch. It pays by the order. A multibatch order is cheaper than ordering each batch separately.
2. It is very likely that a 20,000L reactor is going to cost less/kg output than 10 2,000L ones, IMO. If not nobody would use 20k ones.
3. It is very unlikely that Omeros will manufacture its own monoclonal antibodies for the forseeable future.
The may start producing MCAs about the same time you start shipping fish to Japan and China.
Yet another use for Naso!
Complement inhibition reverses mental losses in preclinical traumatic brain injury models
Researchers at the Medical University of South Carolina provide preclinical evidence that mental losses after traumatic brain injury can be reversed with complement inhibition, even when implemented two months after injury.
MEDICAL UNIVERSITY OF SOUTH CAROLINA
IMAGE: HIPPOCAMPAL SLICES OF AN UNINJURED BRAIN (TOP) OR A BRAIN THREE MONTHS AFTER TBI (BOTTOM). THERE IS AN INCREASE IN ASTROCYTES (GREEN) FOLLOWING A BRAIN INJURY. view more
CREDIT: DR. STEPHEN TOMLINSON OF THE MEDICAL COLLEGE OF WISCONSIN.
Traumatic brain injury (TBI) is a major cause of disability and a risk factor for early-onset dementia. The injury is characterized by a physical insult followed acutely by complement driven neuroinflammation. Complement, a part of the innate immune system that functions both in the brain and throughout the body, enhances the body's ability to fight pathogens, promote inflammation and clear damaged cells. Complement plays a role in the brain, regardless of infection or injury, as it influences brain development and synapse formation. In TBI, complement- induced inflammation partially determines the outcome in the weeks immediately following injury. However, more research is needed to define a role for the complement system in neurodegeneration following head injury, specifically in the long-term, chronic phase of TBI. Furthermore, therapeutic management of TBI patients is limited to the acute phase following injury, as little is known about the link between the initial insult and the chronic neurodegeneration and cognitive decline in the months and years that follow.
Researchers at the Medical University of South Carolina (MUSC), the Ralph H. Johnson VA Medical Center and elsewhere have reported a link between the complement system and the chronic phase of TBI. Their results, published online on Jan. 12 in the Journal of Neuroscience, showed that inhibition of complement at two months after TBI disrupts neurodegeneration and improves cognitive function.
"TBI is associated with cognitive decline and dementia, and there are zero pharmacological treatments to prevent that cognitive decline," said Stephen Tomlinson, Ph.D., a professor and interim chairman of the Department of Microbiology and Immunology, who studies brain injury and the complement system.
"The vast majority of studies that have been done investigating different therapeutics in TBI have all been done with acute treatments, within hours of the initial insult. Our study is significant because we are starting treatments out to two months after TBI."
To understand more fully the timing of complement and chronic TBI, the Tomlinson Lab first looked at the body's response to the damaged area. They showed that certain brain cells, called microglia, destroy neuronal synapses that have been marked by complement for degradation. This process reduces the overall number and density of synapses in the brain. Further, they reported ongoing complement activation up to three months after one initial TBI insult, with expanding neuroinflammation across brain regions. This inflammatory response promotes degeneration of synapses and was predictive of progressive cognitive decline.
The researchers then explored the therapeutic effects of blocking complement. They used a complement inhibitor that specifically targets sites of complement activation and brain cell injury. Inhibiting complement interrupted the decline in brain cell function and reversed mental losses on tasks that evaluate spatial learning and memory, even when delivery of the inhibitor was delayed until two months after the injury.
"One big advantage of our approach is that we do not systemically inhibit complement," said Tomlinson.
"With acute treatments, it is not that big of an issue but chronically treating someone with a complement inhibitor systemically is not optimal because complement does other important things, ranging from host defense to controlling homeostatic and regenerative mechanisms."
Thus far, therapeutic investigations in preclinical models have focused almost entirely on acute treatments for TBI. With this new insight into TBI pathology, the Tomlinson team suggests that all phases of injury, including chronic time points, may be responsive to therapeutic treatments, specifically those involving complement inhibition.
These findings are critical, as rehabilitative interventions are the only available management strategy for TBI to improve cognitive and motor functions. Additionally, cumulative evidence shows that rehabilitation is likely to speed up recovery but not change long-term outcomes.
"It gives us a new way of perceiving TBI management. Really, the only therapy at the moment is rehabilitation therapy, which clinically has very little benefit. We have found that rehabilitation and complement inhibition have additive effects," said Tomlinson.
Looking forward, Tomlinson wants to take the translational approach of complement inhibition in the chronic phase of TBI out further, past that two-month window, and is investigating whether the treatment will still work in mice if it is begun six months to a year out from the initial TBI. Additionally, Tomlinson is developing models of repetitive TBI and plans to investigate anxiety and depressive behaviors in addition to early onset dementia, a significant concern in regard to veterans, soldiers and athletes.
Currently, multiple complement inhibitors are in various stages of clinical development, including those that are targeted specifically to sites of injury and disease. Tomlinson himself is a co-founder of a company that is investigating targeted complement inhibition, leading to the potential of incorporating complement inhibition into the clinic. Thus, studies undertaken in the Tomlinson lab could have deep and lasting impacts at the clinical level, where complement inhibition could eventually help the thousands of patients that suffer from TBI each year.
Founded in 1824 in Charleston, MUSC is the oldest medical school in the South, as well as the state's only integrated, academic health sciences center with a unique charge to serve the state through education, research and patient care. Each year, MUSC educates and trains more than 3,000 students and 700 residents in six colleges: Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy. The state's leader in obtaining biomedical research funds, in fiscal year 2018, MUSC set a new high, bringing in more than $276.5 million. For information on academic programs, visit http://musc.edu.
As the clinical health system of the Medical University of South Carolina, MUSC Health is dedicated to delivering the highest quality patient care available while training generations of competent, compassionate health care providers to serve the people of South Carolina and beyond. Comprising some 1,600 beds, more than 100 outreach sites, the MUSC College of Medicine, the physicians' practice plan and nearly 275 telehealth locations, MUSC Health owns and operates eight hospitals situated in Charleston, Chester, Florence, Lancaster and Marion counties. In 2019, for the fifth consecutive year, U.S. News & World Report named MUSC Health the No. 1 hospital in South Carolina. To learn more about clinical patient services, visit http://muschealth.org.
Serious question - Would aging be similar re effects on the brain as acute brain injury, just spread out over more time? My point being, would Narso help people who have lost cognitive abilities due to "aging?"
Yes, there is some evidence endothelial damage is important in Alzheimers.
In fact, there was a very large trial, years ago, where people's mental abilities were followed for many years and then when they died their brains were studied. There was no correlation between the "plaques" that are though to cause Alzheimers and the exhibit of mental deficits.
And every anti-plaque drug candidate has failed to cure Alzheimers or stop its progression.
Vascular supply is more crucial for the brain because it is the organ that uses the most energy and needs its blood supply. It makes sense that endothelial damage interferes with mental ability.
Someday I expect Omeros to address that AND heart disease.
Think of the wide use of steroid to partly control inflammation. Narso seems to do it better by eliminating the endothelial damage and stopping the thrombi; the TMAs; the many many tiny microscopic clots.
Speaking of using steroid drugs to control inflammation - I'm on my third week of Prednisone drops into my right eye, to prevent inflammation. Inflammation can cause infection even after taking anti-infection drops, which I did for one week. Now I have to taper off of the Prednisone gradually, next week just one drop per day for the week, then I am finished.
Narsoplimab seems to be appropriate for so many indications - but all having endothelial damage and inflammation at the heart of the problem. I hope I live long enough to see Narso appropriately used as treatments for all of these different indications. More and more it seems like a wonder drug - but the interesting thing about it is that it has a limited-in-scope approach to one major manifestation of problems inside our body.
I don't know, but I am wondering if, some day, Greg will be ranked like other famous doctors, like Salk and other pioneers. I've said this before but what I am really waiting for is news that the cancer drug will be good.
Someone on ST says Bank of America is holding a call on Thursday 11th at 10 am with Dr Nelson Chao to discuss TA-TMA landscape and OMER’s clinical data for Narso.
Targeting MASP2 in a mouse model...another potential indication for narso.
Targeted deletions of complement lectin pathway genes improve outcome in traumatic brain injury, with MASP-2 playing a major role
The lectin pathway (LP) of complement activation is believed to contribute to brain inflammation. The study aims to identify the key components of the LP contributing to TBI outcome as possible novel pharmacological targets. We compared the long-term neurological deficits and neuropathology of wild-type mice (WT) to that of mice carrying gene deletions of key LP components after experimental TBI. WT or MASP-2 (Masp2−/−), ficolin-A (Fcna−/−), CL-11 (Colec11−/−), MASP-1/3 (Masp1−/−), MBL-C (Mbl2−/−), MBL-A (Mbl1−/−) or MBL−/− (Mbl1−/−/Mbl2−/−) deficient male C57BL/6J mice were used. Mice underwent sham surgery or TBI by controlled cortical impact. The sensorimotor response was evaluated by neuroscore and beam walk tests weekly for 4 weeks. To obtain a comparative analysis of the functional outcome each transgenic line was rated according to a health score calculated on sensorimotor performance. For selected genotypes, brains were harvested 6 weeks after injury for histopathological analysis. MASP-2−/−, MBL−/− and FCN-A−/− mice had better outcome scores compared to WT. Of these, MASP-2−/− mice had the best recovery after TBI, showing reduced sensorimotor deficits (by 33% at 3 weeks and by 36% at 4 weeks). They also showed higher neuronal density in the lesioned cortex with a 31.5% increase compared to WT. Measurement of LP functional activity in plasma from MASP-2−/− mice revealed the absence of LP functional activity using a C4b deposition assay. The LP critically contributes to the post-traumatic inflammatory pathology following TBI with the highest degree of protection achieved through the absence of the LP key enzyme MASP-2, underlining a therapeutic utility of MASP-2 targeting in TBI.
Narso may be why Greg is not worried about getting old. It might reverse aging too.
What about ED, sexual dysfunction, things like that...that'd be a gigantic market.
And PD too given all the commercials I've been seeing!
I don't see those commercials. What's PD?
To try to understand what might happen after narsoplimab launches, I am studying the launch of Soliris by ALXN in 2007 and what happened.
I have not completed the study or the article, but it is here:
http://www.trustintelligence.com/viewto … 4049#p4049
You will find out, among other things, how few patients they had and that the "most expensive drug in the world" only had a gross margin under 90%, about 10% lower than that for Omidria.
Peyronie's disease.....careful looking it up so the bots don't target you:). I've started seeing many TV commercials across multiple stations, so whoever makes or provides treatment is spending a lot of money.
Good idea about the ALXN article. I commented over there.
Don't have time for looking at that....
BAM raised narso approval probability to 80% from 50% which presumably accounted for the $4 price target increase...although they seems underdone, given whole range of narso indications become more likely once narso is approved for the first one.
I will have more data to present on the Soliris launch by ALXN, on the ALXN thread, today.
From one of the guys on the Chao talk Call now:
Chao was asked whether the availability of narso will increase the number of allogeneic transplants.
Dr. said no.
"He did say that the question is going to be whether Narso is prescribed in moderate TMA cases and not just severe cases.
He also said TMA incidence is about 20% in his practice, although there not being a universal definition of TMA makes this a challenging number to estimate. Consistent w what Greg said. He said that there is reluctance to diagnose TMA bc there is no treatment.
He said they prescribe Soliris but it can be tough because it isn't approved on TMA. "
Will have access to EBMT2021. As you know, the Omeros sponsored presentation on HSCT-TMA (Dr's Perales, Laurence and Rambaldi) is on Sunday. I'll do a video capture and upload to my Drive and post a link.
Thanks a lot, Ed.
Guys like these KOLs are key to ensuring that narsoplimab is adopted quickly by those who treat transplant patients. These front-line doctors need to order narso quickly when their patients need it and stop even considering using Soliris (which can be fatal to their patients).
The EBMT meeting is today and Omer and its KOLs are trying to educate transplant docs.
This slide tell us something about when they treat people and with how much.
I note that 4mg/kg is standard and the treatment for this TA-TMA patient is the typical once per week. Remember aHUS is once a DAY (after an initial "loading dose").
I am still not sure whether for CV19 it is once a week or twice a week.
Seems to me that it would have been best to treat this woman on day 2 or 3.
Here's the link for TIPSters to the Omeros sponsored presentation on Lectin Pathway complement pathophysiology in HSCT-TMA at EBMT2021. Note there is no Q&A at the end as they apparently skipped it or had tech issues.
Thanks for sharing.
Alan, re your #142 just above, I am reminded of the 6 people treated in Bergamo. They were at death's door and Narsoplimab pulled them back and made them better. I assume the same thing here. Greg wants to demonstrate the power of Narsoplimab, by waiting until everything else has failed, and then saving the day.
Which brings me to what you said the other day, re the ISPY trial, in which you were thinking you were unsure how Narsoplimab would look when used on people that were not as ill as those treated in the compassionate use trials. I am assuming that in early stages of sequelae, Narso will be just as effective as it seems to be when used in late stage sequelae.
Are there any examples of drugs that are not that effective when used early on in an illness, but that are effective when used in later stages of the illness?
Good question, Avi, but much more complicated.
If a drug only treats the symptoms, like prednisone (anti-inflammatory steroid) if there is no inflammation from the disease it doesn't prevent it from happening.
Narso inhibits the LP which CAUSES endothelial damage, so narso treats what causes the symptom and will stop if from happening in the first place.
But other treatments like the steroid may look as good as the Narso when the patient only has moderate disease... while the steroid won't stop run-away inflammation that leads to death.
And given the Bergamo 6 results, a short narso treatment seems to protect them for at least 6 months... not that we know the the normal % of people who survive ventilation but have further sequelae afterwards.
These are two new patent applications... apparently to use Narso to treat just about all kidney disease by treating fibrosis (scar tissue that interferes with functioning).
About 10% of all Medicare costs are to treat kidney disease.
OMER wants to treat the kidney, even of the damage is caused by radiologic dye administered to got good kidney imagining. Medicare would likely save money by using narso to make the patients better.
The above is an old 60 Minutes segment on health in people aged 90+.
As you probably know, about half those with diagnoses of Alzheimers don't have plaques and tangles on brain autopsy. And there are lots of people who have normal mental function but when brain is autopsied they do have plaque and tangles (which makes it crazy to continue to try to develop Alzheimer treatments based on reducing plaques and tangles that continue to fail). The reason I posted this is that those with memory and other deficits who did not have plaques and and tangle has hundred and thousands of TMAs, each of which obviously killed some neurons. Narso certainly can't reverse that, but I'd guess reduces EIS would reduce the TMAs.
They replayed this in Nov. 2020 but it is very interesting, especially if you are getting up in years or have relatives that are.
I’d like to know the progression of these TMA as a general function of age, and at what point noticeable cognitive decline occurs. It may be that much younger people are being damaged in a way that is not apparent.
Certainly that is true, yet it is not easy to verify and expensive to do it on "spec" with expensive imagining, because most are like microscopic, perhaps a few to a few 1000 cells dead and cleaned up, leaving an irregular 3D void.
Counting them would be difficult and tedious.
I used to do brain histology on my animals when an experiment ended, removing, freezing, slicing the brain, mounting on slides and then staining them so you can see what is what, staining cell bodies differently than the fatty myelin sheath (wire part)... and then studying them under a microscope to localize where the electrodes had been implanted. Human brains are huge in comparison.
One of the reasons it is not worth the time and money is that, as the 60 Minutes piece said, there are people with lots of damage who don't have significant deficits and, if you found voids, you can't determine whether they are long standing from something that happen 50 years ago, or from last week.
Damage in the brain leads to the damaged cells dying. The do not "heal". But brain FUNCTION is plastic meaning an area in the brain that normally does one thing can be trained to do other things. That is why people who strokes may be able to have therapy to regain some or all of the lost function.
And people with mental deficits can learn ways to better cope. My 93 year old Mother has significant memory problems and it is normal for this to cause frustration that makes it worse. Most of the problems are "retrieval" not storage problems. The memories are there but not easily accessed, especially if not used often.